B-Cell Lymphoma ICYMI

rutherford_s.jpg

Non-Hodgkin lymphomas (NHLs) are cancers that arise in a type of white blood cell called the lymphocyte. NHLs are divided into B- and T-cell subtypes, as well as aggressive and indolent forms. Management varies widely depending on the disease type. We will focus on the most common type of NHL, diffuse large B-cell lymphoma (DLBCL), for which there have been significant treatment advances in recent years. 

DLBCL is curable in about two-thirds of patients using chemoimmunotherapy. The longstanding frontline treatment for this disease has been R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In 2023, an antibody-drug conjugate against the B-cell surface protein CD79b, polatuzumab vedotin, was approved by the US Food and Drug Administration (FDA) in combination with R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone) for newly diagnosed DLBCL based on an improvement in progression-free survival at 2 years in patients with high-risk disease features enrolled in the POLARIX study.

For patients who do not respond to the initial treatment or in whom the disease recurs, the historical standard of care treatment strategy was high-dose chemotherapy followed by autologous stem cell transplant (ASCT). Unfortunately, this approach is not feasible or not successful in a significant percentage of patients with relapsed or refractory DLBCL. 

A newer strategy for DLBCL is chimeric antigen receptor (CAR) T-cell therapy. In this treatment, T cells are collected from a patient and genetically modified to target a protein on the lymphoma cells called CD19. This type of treatment was initially approved in the third-line setting for DLBCL based on the ZUMA-1 (axi-cel), JULIET (tisa-cel), and TRANSCEND (liso-cel) clinical trials. More recently, in 2022, 2 of these agents received approval in the second-line setting in patients who relapse or are refractory to initial treatment within 1 year; axi-cel was approved based on the ZUMA-7 trial and liso-cel was approved based on the TRANSFORM trial. 

Unfortunately, not all patients are eligible for ASCT and CAR T-cell therapy due to factors including age, comorbidities, and disease characteristics. Some patients prefer alternative therapies based on the potential side effects of CAR T-cell therapy and ASCT. Toxicities associated with CAR T-cell therapy include an inflammatory response called cytokine release syndrome and neurologic events. 

For patients who are not eligible for or who relapse after ASCT or CAR T-cell therapy, several alternative treatment options are FDA approved. Novel strategies include polatuzumab vedotin with bendamustine and rituximab and tafasitamab plus lenalidomide. Tafasitamab is a monoclonal antibody against CD19 and lenalidomide is an oral anticancer agent originally approved for use in multiple myeloma. Lenalidomide is also effective and commonly used in other NHL subtypes. 

In 2023, a new category of treatment called bispecific antibodies was approved in patients with DLBCL in whom the disease recurs after 2 lines of therapy. These drugs (epcoritamab and glofitamab) are a form of immunotherapy that connects B cells with T cells to enable a person’s own immune system to better fight the lymphoma. While these drugs can have similar toxicities as CAR T-cell therapy, the severity and incidence are much lower. In contrast to CAR T-cell therapy, which requires only 1 infusion, these drugs are given regularly in either subcutaneous or intravenous form for several months. 

Two other FDA-approved treatment options for relapsed and refractory DLBCL are loncastuximab tesirine, an antibody-drug conjugate targeting CD19 with approval based on the results of the LOTIS-2 trial, and the oral selective inhibitor of nuclear export called selinexor, based on the results from the SADAL trial. Selinexor is a fully synthetic small-molecule compound, developed by means of a structure-based drug design process known as induced-fit docking. It binds to a cysteine residue in the nuclear export signal groove of exportin 1. Selinexor is approved for use in adults with relapsed or refractory DLBCL who have received at least 2 types of systemic therapy. Trials investigating these agents in combination with other novel treatments are ongoing. 

The treatment landscape for DLBCL has changed markedly over the past several years. Therapies can be tailored for individual patients based on their disease status and characteristics, comorbidities, and treatment preferences. Research with novel strategies continues with the goal of a cure for all patients diagnosed with DLBCL.  

rutherford_s.jpg

Non-Hodgkin lymphomas (NHLs) are cancers that arise in a type of white blood cell called the lymphocyte. NHLs are divided into B- and T-cell subtypes, as well as aggressive and indolent forms. Management varies widely depending on the disease type. We will focus on the most common type of NHL, diffuse large B-cell lymphoma (DLBCL), for which there have been significant treatment advances in recent years. 

DLBCL is curable in about two-thirds of patients using chemoimmunotherapy. The longstanding frontline treatment for this disease has been R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In 2023, an antibody-drug conjugate against the B-cell surface protein CD79b, polatuzumab vedotin, was approved by the US Food and Drug Administration (FDA) in combination with R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone) for newly diagnosed DLBCL based on an improvement in progression-free survival at 2 years in patients with high-risk disease features enrolled in the POLARIX study.

For patients who do not respond to the initial treatment or in whom the disease recurs, the historical standard of care treatment strategy was high-dose chemotherapy followed by autologous stem cell transplant (ASCT). Unfortunately, this approach is not feasible or not successful in a significant percentage of patients with relapsed or refractory DLBCL. 

A newer strategy for DLBCL is chimeric antigen receptor (CAR) T-cell therapy. In this treatment, T cells are collected from a patient and genetically modified to target a protein on the lymphoma cells called CD19. This type of treatment was initially approved in the third-line setting for DLBCL based on the ZUMA-1 (axi-cel), JULIET (tisa-cel), and TRANSCEND (liso-cel) clinical trials. More recently, in 2022, 2 of these agents received approval in the second-line setting in patients who relapse or are refractory to initial treatment within 1 year; axi-cel was approved based on the ZUMA-7 trial and liso-cel was approved based on the TRANSFORM trial. 

Unfortunately, not all patients are eligible for ASCT and CAR T-cell therapy due to factors including age, comorbidities, and disease characteristics. Some patients prefer alternative therapies based on the potential side effects of CAR T-cell therapy and ASCT. Toxicities associated with CAR T-cell therapy include an inflammatory response called cytokine release syndrome and neurologic events. 

For patients who are not eligible for or who relapse after ASCT or CAR T-cell therapy, several alternative treatment options are FDA approved. Novel strategies include polatuzumab vedotin with bendamustine and rituximab and tafasitamab plus lenalidomide. Tafasitamab is a monoclonal antibody against CD19 and lenalidomide is an oral anticancer agent originally approved for use in multiple myeloma. Lenalidomide is also effective and commonly used in other NHL subtypes. 

In 2023, a new category of treatment called bispecific antibodies was approved in patients with DLBCL in whom the disease recurs after 2 lines of therapy. These drugs (epcoritamab and glofitamab) are a form of immunotherapy that connects B cells with T cells to enable a person’s own immune system to better fight the lymphoma. While these drugs can have similar toxicities as CAR T-cell therapy, the severity and incidence are much lower. In contrast to CAR T-cell therapy, which requires only 1 infusion, these drugs are given regularly in either subcutaneous or intravenous form for several months. 

Two other FDA-approved treatment options for relapsed and refractory DLBCL are loncastuximab tesirine, an antibody-drug conjugate targeting CD19 with approval based on the results of the LOTIS-2 trial, and the oral selective inhibitor of nuclear export called selinexor, based on the results from the SADAL trial. Selinexor is a fully synthetic small-molecule compound, developed by means of a structure-based drug design process known as induced-fit docking. It binds to a cysteine residue in the nuclear export signal groove of exportin 1. Selinexor is approved for use in adults with relapsed or refractory DLBCL who have received at least 2 types of systemic therapy. Trials investigating these agents in combination with other novel treatments are ongoing. 

The treatment landscape for DLBCL has changed markedly over the past several years. Therapies can be tailored for individual patients based on their disease status and characteristics, comorbidities, and treatment preferences. Research with novel strategies continues with the goal of a cure for all patients diagnosed with DLBCL.  

rutherford_s.jpg

Non-Hodgkin lymphomas (NHLs) are cancers that arise in a type of white blood cell called the lymphocyte. NHLs are divided into B- and T-cell subtypes, as well as aggressive and indolent forms. Management varies widely depending on the disease type. We will focus on the most common type of NHL, diffuse large B-cell lymphoma (DLBCL), for which there have been significant treatment advances in recent years. 

DLBCL is curable in about two-thirds of patients using chemoimmunotherapy. The longstanding frontline treatment for this disease has been R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). In 2023, an antibody-drug conjugate against the B-cell surface protein CD79b, polatuzumab vedotin, was approved by the US Food and Drug Administration (FDA) in combination with R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone) for newly diagnosed DLBCL based on an improvement in progression-free survival at 2 years in patients with high-risk disease features enrolled in the POLARIX study.

For patients who do not respond to the initial treatment or in whom the disease recurs, the historical standard of care treatment strategy was high-dose chemotherapy followed by autologous stem cell transplant (ASCT). Unfortunately, this approach is not feasible or not successful in a significant percentage of patients with relapsed or refractory DLBCL. 

A newer strategy for DLBCL is chimeric antigen receptor (CAR) T-cell therapy. In this treatment, T cells are collected from a patient and genetically modified to target a protein on the lymphoma cells called CD19. This type of treatment was initially approved in the third-line setting for DLBCL based on the ZUMA-1 (axi-cel), JULIET (tisa-cel), and TRANSCEND (liso-cel) clinical trials. More recently, in 2022, 2 of these agents received approval in the second-line setting in patients who relapse or are refractory to initial treatment within 1 year; axi-cel was approved based on the ZUMA-7 trial and liso-cel was approved based on the TRANSFORM trial. 

Unfortunately, not all patients are eligible for ASCT and CAR T-cell therapy due to factors including age, comorbidities, and disease characteristics. Some patients prefer alternative therapies based on the potential side effects of CAR T-cell therapy and ASCT. Toxicities associated with CAR T-cell therapy include an inflammatory response called cytokine release syndrome and neurologic events. 

For patients who are not eligible for or who relapse after ASCT or CAR T-cell therapy, several alternative treatment options are FDA approved. Novel strategies include polatuzumab vedotin with bendamustine and rituximab and tafasitamab plus lenalidomide. Tafasitamab is a monoclonal antibody against CD19 and lenalidomide is an oral anticancer agent originally approved for use in multiple myeloma. Lenalidomide is also effective and commonly used in other NHL subtypes. 

In 2023, a new category of treatment called bispecific antibodies was approved in patients with DLBCL in whom the disease recurs after 2 lines of therapy. These drugs (epcoritamab and glofitamab) are a form of immunotherapy that connects B cells with T cells to enable a person’s own immune system to better fight the lymphoma. While these drugs can have similar toxicities as CAR T-cell therapy, the severity and incidence are much lower. In contrast to CAR T-cell therapy, which requires only 1 infusion, these drugs are given regularly in either subcutaneous or intravenous form for several months. 

Two other FDA-approved treatment options for relapsed and refractory DLBCL are loncastuximab tesirine, an antibody-drug conjugate targeting CD19 with approval based on the results of the LOTIS-2 trial, and the oral selective inhibitor of nuclear export called selinexor, based on the results from the SADAL trial. Selinexor is a fully synthetic small-molecule compound, developed by means of a structure-based drug design process known as induced-fit docking. It binds to a cysteine residue in the nuclear export signal groove of exportin 1. Selinexor is approved for use in adults with relapsed or refractory DLBCL who have received at least 2 types of systemic therapy. Trials investigating these agents in combination with other novel treatments are ongoing. 

The treatment landscape for DLBCL has changed markedly over the past several years. Therapies can be tailored for individual patients based on their disease status and characteristics, comorbidities, and treatment preferences. Research with novel strategies continues with the goal of a cure for all patients diagnosed with DLBCL.  

While chimeric antigen receptor (CAR) T-cell therapy has transformed the management of large B-cell lymphoma (LBCL), the majority of patients will ultimately relapse. Efforts to identify predictors of response remain an active area of investigation. One key variable that has been postulated to influence CAR T-cell outcomes is pretreatment bendamustine exposure. Specifically, there has been concern that the lymphodepleting effects of bendamustine could affect T-cell fitness, thus impairing CAR T-cell response. While consensus guidelines have recommended avoiding bendamustine prior to lymphocyte collection, clear data have been lacking. A recent retrospective, multicenter study, which included patients from seven European sites, reported outcomes based on prior bendamustine exposure (Iacoboni et al). In this study, 439 patients with relapsed or refractory LBCL, who received anti-CD19 commercial CAR T-cell therapy after two or more prior treatment lines of therapy, were included. Of these patients, 80 had received prior bendamustine. The authors found that patients recently exposed to bendamustine (< 9 months), vs bendamustine-naive patients, had a significantly lower overall response rate (40% vs 66%; P = .01), overall survival (OS; adjusted hazard ratio [aHR] 2.11; P < .01), and progression-free survival (PFS; aHR 1.82; P < .01) after CAR T-cell infusion. These differences remained significant after inverse probability treatment weighting and propensity score matching. Of note, the authors did not find that the cumulative dose of bendamustine affected outcomes. The authors also identified that, while the risk for cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome was similar between the groups, hematologic toxicity and severe infections were increased in the bendamustine-exposed patients. These data support the recommendation to avoid bendamustine treatment prior to CAR T-cell apheresis. While treatment regimens such as polatuzumab plus bendamustine and rituximab are available in the relapsed setting for LBCL,¹ this regimen should be reserved for post CAR T-cell relapse or for patients not planning to proceed with cellular therapy. The impact of bendamustine exposure on other immune-mediated therapies, such as bispecific antibodies, remains unknown.

Quantitative PET/CT biomarkers have also emerged as predictors of response in diffuse large B-cell lymphoma (DLBCL). A key variable of interest includes total metabolic tumor volume (MTV), which refers to the total volume of tumor with metabolic uptake. While prior studies have demonstrated a correlation of MTV on outcomes following treatment with chemotherapy and CAR T-cell therapy,^2,3 the effect of PET/CT biomarkers on outcomes with other novel agents remains poorly described. A recent study by Alderuccio and colleagues explored the predictive power of PET/CT biomarkers on outcomes in a clinical trial cohort of patients treated with the antibody drug conjugate loncastuximab tesirine. This post hoc analysis reviewed the screening PET/CT scans of 138 patients with relapsed or refractory DLBCL treated with two or more prior systemic therapy lines who received loncastuximab tesirine in LOTIS-2<.⁴ The authors found that an MTV ≥ 96 mL was significantly associated with failure to achieve a complete metabolic response (adjusted odds ratio 5.42; P = .002). Patients with an MTV ≥ 96 mL vs < 96 mL also had a shorter PFS (aHR 2.68; P = .002) and OS (aHR 3.09; P < .0001). In line with prior studies, this analysis demonstrates that baseline MTV has the potential to provide robust risk-stratification and confirms the value of PET/CT biomarkers in DLBCL across treatment types.

This month, the results of the phase 2 TARMAC study, which evaluated treatment with ibrutinib in combination with tisagenlecleucel, were also published. This study included 20 patients with relapsed/refractory mantle cell lymphoma (MCL) who had received one or more prior lines of therapy, including 50% with prior Bruton tyrosine kinase inhibitor (BTKi) exposure. Ibrutinib was initiated prior to leukapheresis and continued through CAR T-cell manufacturing and for at least 6 months post tisagenlecleucel infusion. At 4 months post infusion, the overall and complete response rates were 80% each. Patients without and with prior BTKi exposure had complete response rates of 90% and 70%, respectively. At a median follow-up of 13 months, the estimated 12-month PFS was 75% and OS was 100%. Grades 1-2 and grade 3 cytokine-release syndrome rates were 55% and 20%, respectively, and grade 1-2 immune effector cell–associated neurotoxicity syndrome was seen in 10% of patients. The authors also demonstrated that markers of T-cell exhaustion were decreased in patients with longer ibrutinib exposure prior to leukapheresis. Also of note, the three patients with recent bendamustine therapy did not receive a durable response. Although this is a small study without a control arm, this study provides rationale for the potential advantage of combining BTKi with CAR T-cell therapy, even among patients with prior BTKi exposure.

Additional References

1.       Sehn LH, Hertzberg M, Opat S, et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022;6(2):533-543. doi: 10.1182/bloodadvances.2021005794

2.       Vercellino L, Cottereau AS, Casasnovas O, et al. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood. 2020;135(16):1396-1405. doi: 10.1182/blood.2019003526

3.       Dean EA, Mhaskar RS, Lu H, et al. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020;4(14):3268-3276. doi: 10.1182/bloodadvances.2020001900

4.       Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800. doi:

While chimeric antigen receptor (CAR) T-cell therapy has transformed the management of large B-cell lymphoma (LBCL), the majority of patients will ultimately relapse. Efforts to identify predictors of response remain an active area of investigation. One key variable that has been postulated to influence CAR T-cell outcomes is pretreatment bendamustine exposure. Specifically, there has been concern that the lymphodepleting effects of bendamustine could affect T-cell fitness, thus impairing CAR T-cell response. While consensus guidelines have recommended avoiding bendamustine prior to lymphocyte collection, clear data have been lacking. A recent retrospective, multicenter study, which included patients from seven European sites, reported outcomes based on prior bendamustine exposure (Iacoboni et al). In this study, 439 patients with relapsed or refractory LBCL, who received anti-CD19 commercial CAR T-cell therapy after two or more prior treatment lines of therapy, were included. Of these patients, 80 had received prior bendamustine. The authors found that patients recently exposed to bendamustine (< 9 months), vs bendamustine-naive patients, had a significantly lower overall response rate (40% vs 66%; P = .01), overall survival (OS; adjusted hazard ratio [aHR] 2.11; P < .01), and progression-free survival (PFS; aHR 1.82; P < .01) after CAR T-cell infusion. These differences remained significant after inverse probability treatment weighting and propensity score matching. Of note, the authors did not find that the cumulative dose of bendamustine affected outcomes. The authors also identified that, while the risk for cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome was similar between the groups, hematologic toxicity and severe infections were increased in the bendamustine-exposed patients. These data support the recommendation to avoid bendamustine treatment prior to CAR T-cell apheresis. While treatment regimens such as polatuzumab plus bendamustine and rituximab are available in the relapsed setting for LBCL,¹ this regimen should be reserved for post CAR T-cell relapse or for patients not planning to proceed with cellular therapy. The impact of bendamustine exposure on other immune-mediated therapies, such as bispecific antibodies, remains unknown.

Quantitative PET/CT biomarkers have also emerged as predictors of response in diffuse large B-cell lymphoma (DLBCL). A key variable of interest includes total metabolic tumor volume (MTV), which refers to the total volume of tumor with metabolic uptake. While prior studies have demonstrated a correlation of MTV on outcomes following treatment with chemotherapy and CAR T-cell therapy,^2,3 the effect of PET/CT biomarkers on outcomes with other novel agents remains poorly described. A recent study by Alderuccio and colleagues explored the predictive power of PET/CT biomarkers on outcomes in a clinical trial cohort of patients treated with the antibody drug conjugate loncastuximab tesirine. This post hoc analysis reviewed the screening PET/CT scans of 138 patients with relapsed or refractory DLBCL treated with two or more prior systemic therapy lines who received loncastuximab tesirine in LOTIS-2<.⁴ The authors found that an MTV ≥ 96 mL was significantly associated with failure to achieve a complete metabolic response (adjusted odds ratio 5.42; P = .002). Patients with an MTV ≥ 96 mL vs < 96 mL also had a shorter PFS (aHR 2.68; P = .002) and OS (aHR 3.09; P < .0001). In line with prior studies, this analysis demonstrates that baseline MTV has the potential to provide robust risk-stratification and confirms the value of PET/CT biomarkers in DLBCL across treatment types.

This month, the results of the phase 2 TARMAC study, which evaluated treatment with ibrutinib in combination with tisagenlecleucel, were also published. This study included 20 patients with relapsed/refractory mantle cell lymphoma (MCL) who had received one or more prior lines of therapy, including 50% with prior Bruton tyrosine kinase inhibitor (BTKi) exposure. Ibrutinib was initiated prior to leukapheresis and continued through CAR T-cell manufacturing and for at least 6 months post tisagenlecleucel infusion. At 4 months post infusion, the overall and complete response rates were 80% each. Patients without and with prior BTKi exposure had complete response rates of 90% and 70%, respectively. At a median follow-up of 13 months, the estimated 12-month PFS was 75% and OS was 100%. Grades 1-2 and grade 3 cytokine-release syndrome rates were 55% and 20%, respectively, and grade 1-2 immune effector cell–associated neurotoxicity syndrome was seen in 10% of patients. The authors also demonstrated that markers of T-cell exhaustion were decreased in patients with longer ibrutinib exposure prior to leukapheresis. Also of note, the three patients with recent bendamustine therapy did not receive a durable response. Although this is a small study without a control arm, this study provides rationale for the potential advantage of combining BTKi with CAR T-cell therapy, even among patients with prior BTKi exposure.

Additional References

1.       Sehn LH, Hertzberg M, Opat S, et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022;6(2):533-543. doi: 10.1182/bloodadvances.2021005794

2.       Vercellino L, Cottereau AS, Casasnovas O, et al. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood. 2020;135(16):1396-1405. doi: 10.1182/blood.2019003526

3.       Dean EA, Mhaskar RS, Lu H, et al. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020;4(14):3268-3276. doi: 10.1182/bloodadvances.2020001900

4.       Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800. doi:

While chimeric antigen receptor (CAR) T-cell therapy has transformed the management of large B-cell lymphoma (LBCL), the majority of patients will ultimately relapse. Efforts to identify predictors of response remain an active area of investigation. One key variable that has been postulated to influence CAR T-cell outcomes is pretreatment bendamustine exposure. Specifically, there has been concern that the lymphodepleting effects of bendamustine could affect T-cell fitness, thus impairing CAR T-cell response. While consensus guidelines have recommended avoiding bendamustine prior to lymphocyte collection, clear data have been lacking. A recent retrospective, multicenter study, which included patients from seven European sites, reported outcomes based on prior bendamustine exposure (Iacoboni et al). In this study, 439 patients with relapsed or refractory LBCL, who received anti-CD19 commercial CAR T-cell therapy after two or more prior treatment lines of therapy, were included. Of these patients, 80 had received prior bendamustine. The authors found that patients recently exposed to bendamustine (< 9 months), vs bendamustine-naive patients, had a significantly lower overall response rate (40% vs 66%; P = .01), overall survival (OS; adjusted hazard ratio [aHR] 2.11; P < .01), and progression-free survival (PFS; aHR 1.82; P < .01) after CAR T-cell infusion. These differences remained significant after inverse probability treatment weighting and propensity score matching. Of note, the authors did not find that the cumulative dose of bendamustine affected outcomes. The authors also identified that, while the risk for cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome was similar between the groups, hematologic toxicity and severe infections were increased in the bendamustine-exposed patients. These data support the recommendation to avoid bendamustine treatment prior to CAR T-cell apheresis. While treatment regimens such as polatuzumab plus bendamustine and rituximab are available in the relapsed setting for LBCL,¹ this regimen should be reserved for post CAR T-cell relapse or for patients not planning to proceed with cellular therapy. The impact of bendamustine exposure on other immune-mediated therapies, such as bispecific antibodies, remains unknown.

Quantitative PET/CT biomarkers have also emerged as predictors of response in diffuse large B-cell lymphoma (DLBCL). A key variable of interest includes total metabolic tumor volume (MTV), which refers to the total volume of tumor with metabolic uptake. While prior studies have demonstrated a correlation of MTV on outcomes following treatment with chemotherapy and CAR T-cell therapy,^2,3 the effect of PET/CT biomarkers on outcomes with other novel agents remains poorly described. A recent study by Alderuccio and colleagues explored the predictive power of PET/CT biomarkers on outcomes in a clinical trial cohort of patients treated with the antibody drug conjugate loncastuximab tesirine. This post hoc analysis reviewed the screening PET/CT scans of 138 patients with relapsed or refractory DLBCL treated with two or more prior systemic therapy lines who received loncastuximab tesirine in LOTIS-2<.⁴ The authors found that an MTV ≥ 96 mL was significantly associated with failure to achieve a complete metabolic response (adjusted odds ratio 5.42; P = .002). Patients with an MTV ≥ 96 mL vs < 96 mL also had a shorter PFS (aHR 2.68; P = .002) and OS (aHR 3.09; P < .0001). In line with prior studies, this analysis demonstrates that baseline MTV has the potential to provide robust risk-stratification and confirms the value of PET/CT biomarkers in DLBCL across treatment types.

This month, the results of the phase 2 TARMAC study, which evaluated treatment with ibrutinib in combination with tisagenlecleucel, were also published. This study included 20 patients with relapsed/refractory mantle cell lymphoma (MCL) who had received one or more prior lines of therapy, including 50% with prior Bruton tyrosine kinase inhibitor (BTKi) exposure. Ibrutinib was initiated prior to leukapheresis and continued through CAR T-cell manufacturing and for at least 6 months post tisagenlecleucel infusion. At 4 months post infusion, the overall and complete response rates were 80% each. Patients without and with prior BTKi exposure had complete response rates of 90% and 70%, respectively. At a median follow-up of 13 months, the estimated 12-month PFS was 75% and OS was 100%. Grades 1-2 and grade 3 cytokine-release syndrome rates were 55% and 20%, respectively, and grade 1-2 immune effector cell–associated neurotoxicity syndrome was seen in 10% of patients. The authors also demonstrated that markers of T-cell exhaustion were decreased in patients with longer ibrutinib exposure prior to leukapheresis. Also of note, the three patients with recent bendamustine therapy did not receive a durable response. Although this is a small study without a control arm, this study provides rationale for the potential advantage of combining BTKi with CAR T-cell therapy, even among patients with prior BTKi exposure.

Additional References

1.       Sehn LH, Hertzberg M, Opat S, et al. Polatuzumab vedotin plus bendamustine and rituximab in relapsed/refractory DLBCL: survival update and new extension cohort data. Blood Adv. 2022;6(2):533-543. doi: 10.1182/bloodadvances.2021005794

2.       Vercellino L, Cottereau AS, Casasnovas O, et al. High total metabolic tumor volume at baseline predicts survival independent of response to therapy. Blood. 2020;135(16):1396-1405. doi: 10.1182/blood.2019003526

3.       Dean EA, Mhaskar RS, Lu H, et al. High metabolic tumor volume is associated with decreased efficacy of axicabtagene ciloleucel in large B-cell lymphoma. Blood Adv. 2020;4(14):3268-3276. doi: 10.1182/bloodadvances.2020001900

4.       Caimi PF, Ai W, Alderuccio JP, et al. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021;22(6):790-800. doi:

Patients with relapsed diffuse large B cell lymphoma (DLBCL) who achieve a complete remission from interim chemotherapy while awaiting secondary chimeric antigen receptor (CAR) T cell therapy show significantly better outcomes if they then receive conventional autologous stem cell transplantation (auto-HCT), compared with CAR T therapy.

“In patients with relapsed DLBCL in a complete remission, treatment with auto-HCT is associated with a lower rate of relapse/progression, and a longer progression-free survival [versus CAR T therapy],” said first author Mazyar Shadman, MD, MPH, of the Division of Medical Oncology, University of Washington, Seattle.

“The data support utilization of auto-HCT in patients with relapsed LBCL achieving a complete response,” he said.

The findings were presented at the annual meeting of the American Society of Hematology in San Diego.

While approximately 60% of patients with DLBCL are successfully treated after an initial anthracycline-based and rituximab-containing chemotherapy regimen, those who do not improve have poorer outcomes, and CAR T-cell therapy has emerged as the standard of care for those patients, based on results from the ZUMA-7 and TRANSFORM clinical trials.

But with delays in accessing CAR T quite common, patients will often receive interim chemotherapy while awaiting referral to a CAR T center, and occasionally, usually unexpectedly, some will achieve a partial or complete response.

In previous research involving patients who achieved a partial remission in such interim cases, Dr. Shadman and colleagues demonstrated that auto-HCT had favorable outcomes, compared with those who received CAR T therapy.

For the new retrospective, real-world analysis, the authors compared outcomes with the treatment options among 360 patients between the ages of 18 and 75 who were enrolled in the Center for International Blood & Marrow Transplant Research registry and had received auto-HCT or CAR T therapy after achieving a complete remission following salvage chemotherapy.

Of those receiving CAR-T cell therapy, most (53.2%) received tisagenlecleucel (tisa-cel), followed by axicabtagene ciloleucel (axi-cel, 45.6%) and lisocabtagene maraleucel (liso-cel, 1.3%), between 2018 and 2021, while 281 patients were treated with auto-HCT between 2015 and 2021.

With a median follow-up of 49.7 months (range 3.0-94.4) for auto-HCT and 24.7 months (range 3.3-49.4) for CAR-T, a univariate analysis showed the rate of 2-year progression free survival was 66.2% in the auto-HCT group and 47.8% in the CAR T group (P < .001).

The results also favored auto-HCT for 2-year progression/relapse, with a cumulative incidence of 27.8% with auto-HCT versus 48% with CAR T (P < .001), and the 2-year overall survival was higher with auto-HCT (78.9% vs. 65.6%; P = .037).

After adjustment in multivariable analysis adjusting for relevant clinical variables, auto-HCT versus CAR T remained associated with a lower risk of relapse or progression (HR 2.18; P < .0001) and an improved progression-free survival (HR 1.83; P = .0011), with no significant differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).

Deaths occurred among 85 patients in the auto-HCT group and 25 in the CAR T cohort, with lymphoma being the main cause of death in both groups (60% and 68%, respectively).

While 37 (13.2%) of auto-HCT patients later received subsequent CAR-T therapy, no patients receiving CAR-T had subsequent auto-HCT.

There were no differences between the CAR-T and auto-HST groups in rates of 2-year treatment-related mortality (4.1% vs. 5.9%; P = .673).

A subanalysis of those who had treatment failure at 12 months, (CAR-T = 57 and auto-HCT = 163) showed that those receiving CAR-T therapy had a higher 2-year relapse rate (46.3% vs. 25%; P < .001); an inferior 2-year progression-free survival rate (48.4% vs. 68.2%; P = .001) compared with auto-HCT, while there were no significant differences between the groups in terms of 2-year overall survival or treatment-related mortality.

After a multivariable analysis adjusting for relevant clinical factors, CAR-T therapy remained associated with higher risk of relapse (HR 2.18; P < .0001) and an inferior progression-free survival (HR 1.83; P = .0011) compared with auto-HCT, with no differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).

“These results are consistent with our previously reported findings, indicating higher efficacy of auto-HCT compared with CAR T in patients with partial remission,” Dr. Shadman said.

In addition to the study’s being a retrospective analysis, limitations include that more than half of patients in the CAR T cohort received tisa-cel, which could have lower efficacy compared with other approved CAR T therapies, Dr. Shadman noted.

“A repeat analysis by including more patients treated with axi-cel or liso-cel may address this issue in the future,” he said.

Discussing the results in a press briefing, Dr. Shadman underscored that “there is no question the choice of therapy for these DLBCL patients with primary refractory disease should be second-line CAR T therapy — we are not suggesting that those patients should be sent for auto-HCT,” he said.

“What we are saying is, in real-world practice ... patients may need chemotherapy treatment in the interim (awaiting CAR T treatment), and we don’t expect these patients to respond to those cycles because they have already shown us that they don’t do well with chemotherapy — however some do respond and can go into complete remission.”

The question then becomes whether patients at that point will fare better with CAR T or auto-HCT, and the results indicate that “auto-HCT gives those patients a pretty solid remission that looks better than [that with] CAR T therapy.”

Dr. Shadman noted that the results serve to inform or confirm key clinical practices, including “in patients with late relapses, after 12 months, auto-HCT should remain the standard of care.

“In patients with primary refractory disease or early relapse, CAR T should be the goal of therapy and improving access to CAR T should remain a priority.

“In the subset of patients who achieve a CR with interim treatment, a discussion about the possibility of utilizing auto-HCT seems reasonable and can provide another curative option for some patients while keeping CAR-T as a backup treatment plan in case of auto-HCT failure.”

Commenting on the study, Jonathan W. Friedberg, MD, the Samuel Durand Professor of Medicine and director of the Wilmot Cancer Institute, University of Rochester, New York, said, “these findings confirm utility of auto-HCT in patients who achieve a CR.”

However, “the problem is that only a small fraction of patients achieve CR in this situation, and we do not know who they are going to be at time of relapse,” he told this news organization.

He agreed that “given robust randomized trials showing overall survival benefit of CAR-T compared to auto-HCT in patients with high risk relapsed DLBCL, CAR-T treatment should remain the current standard.

“However, these current results help to confirm the strategy for management of low- risk (late) relapses and indicate that auto-HCT still has a place for these patients if they achieve CR with salvage therapy.”

Dr. Shadman reported relationships with ADC therapeutics, Bristol Myers Squibb, Genmab, Lilly, Vincerx, Kite (Gilead), Janssen, Fate Therapeutics, MorphoSys/Incyte, AstraZeneca, BeiGene, Pharmacyclics, Mustang Bio, AbbVie, Genentech, MEI Pharma, Regeneron, and TG Therapeutics. Dr. Friedberg had no disclosures to report.

Patients with relapsed diffuse large B cell lymphoma (DLBCL) who achieve a complete remission from interim chemotherapy while awaiting secondary chimeric antigen receptor (CAR) T cell therapy show significantly better outcomes if they then receive conventional autologous stem cell transplantation (auto-HCT), compared with CAR T therapy.

“In patients with relapsed DLBCL in a complete remission, treatment with auto-HCT is associated with a lower rate of relapse/progression, and a longer progression-free survival [versus CAR T therapy],” said first author Mazyar Shadman, MD, MPH, of the Division of Medical Oncology, University of Washington, Seattle.

“The data support utilization of auto-HCT in patients with relapsed LBCL achieving a complete response,” he said.

The findings were presented at the annual meeting of the American Society of Hematology in San Diego.

While approximately 60% of patients with DLBCL are successfully treated after an initial anthracycline-based and rituximab-containing chemotherapy regimen, those who do not improve have poorer outcomes, and CAR T-cell therapy has emerged as the standard of care for those patients, based on results from the ZUMA-7 and TRANSFORM clinical trials.

But with delays in accessing CAR T quite common, patients will often receive interim chemotherapy while awaiting referral to a CAR T center, and occasionally, usually unexpectedly, some will achieve a partial or complete response.

In previous research involving patients who achieved a partial remission in such interim cases, Dr. Shadman and colleagues demonstrated that auto-HCT had favorable outcomes, compared with those who received CAR T therapy.

For the new retrospective, real-world analysis, the authors compared outcomes with the treatment options among 360 patients between the ages of 18 and 75 who were enrolled in the Center for International Blood & Marrow Transplant Research registry and had received auto-HCT or CAR T therapy after achieving a complete remission following salvage chemotherapy.

Of those receiving CAR-T cell therapy, most (53.2%) received tisagenlecleucel (tisa-cel), followed by axicabtagene ciloleucel (axi-cel, 45.6%) and lisocabtagene maraleucel (liso-cel, 1.3%), between 2018 and 2021, while 281 patients were treated with auto-HCT between 2015 and 2021.

With a median follow-up of 49.7 months (range 3.0-94.4) for auto-HCT and 24.7 months (range 3.3-49.4) for CAR-T, a univariate analysis showed the rate of 2-year progression free survival was 66.2% in the auto-HCT group and 47.8% in the CAR T group (P < .001).

The results also favored auto-HCT for 2-year progression/relapse, with a cumulative incidence of 27.8% with auto-HCT versus 48% with CAR T (P < .001), and the 2-year overall survival was higher with auto-HCT (78.9% vs. 65.6%; P = .037).

After adjustment in multivariable analysis adjusting for relevant clinical variables, auto-HCT versus CAR T remained associated with a lower risk of relapse or progression (HR 2.18; P < .0001) and an improved progression-free survival (HR 1.83; P = .0011), with no significant differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).

Deaths occurred among 85 patients in the auto-HCT group and 25 in the CAR T cohort, with lymphoma being the main cause of death in both groups (60% and 68%, respectively).

While 37 (13.2%) of auto-HCT patients later received subsequent CAR-T therapy, no patients receiving CAR-T had subsequent auto-HCT.

There were no differences between the CAR-T and auto-HST groups in rates of 2-year treatment-related mortality (4.1% vs. 5.9%; P = .673).

A subanalysis of those who had treatment failure at 12 months, (CAR-T = 57 and auto-HCT = 163) showed that those receiving CAR-T therapy had a higher 2-year relapse rate (46.3% vs. 25%; P < .001); an inferior 2-year progression-free survival rate (48.4% vs. 68.2%; P = .001) compared with auto-HCT, while there were no significant differences between the groups in terms of 2-year overall survival or treatment-related mortality.

After a multivariable analysis adjusting for relevant clinical factors, CAR-T therapy remained associated with higher risk of relapse (HR 2.18; P < .0001) and an inferior progression-free survival (HR 1.83; P = .0011) compared with auto-HCT, with no differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).

“These results are consistent with our previously reported findings, indicating higher efficacy of auto-HCT compared with CAR T in patients with partial remission,” Dr. Shadman said.

In addition to the study’s being a retrospective analysis, limitations include that more than half of patients in the CAR T cohort received tisa-cel, which could have lower efficacy compared with other approved CAR T therapies, Dr. Shadman noted.

“A repeat analysis by including more patients treated with axi-cel or liso-cel may address this issue in the future,” he said.

Discussing the results in a press briefing, Dr. Shadman underscored that “there is no question the choice of therapy for these DLBCL patients with primary refractory disease should be second-line CAR T therapy — we are not suggesting that those patients should be sent for auto-HCT,” he said.

“What we are saying is, in real-world practice ... patients may need chemotherapy treatment in the interim (awaiting CAR T treatment), and we don’t expect these patients to respond to those cycles because they have already shown us that they don’t do well with chemotherapy — however some do respond and can go into complete remission.”

The question then becomes whether patients at that point will fare better with CAR T or auto-HCT, and the results indicate that “auto-HCT gives those patients a pretty solid remission that looks better than [that with] CAR T therapy.”

Dr. Shadman noted that the results serve to inform or confirm key clinical practices, including “in patients with late relapses, after 12 months, auto-HCT should remain the standard of care.

“In patients with primary refractory disease or early relapse, CAR T should be the goal of therapy and improving access to CAR T should remain a priority.

“In the subset of patients who achieve a CR with interim treatment, a discussion about the possibility of utilizing auto-HCT seems reasonable and can provide another curative option for some patients while keeping CAR-T as a backup treatment plan in case of auto-HCT failure.”

Commenting on the study, Jonathan W. Friedberg, MD, the Samuel Durand Professor of Medicine and director of the Wilmot Cancer Institute, University of Rochester, New York, said, “these findings confirm utility of auto-HCT in patients who achieve a CR.”

However, “the problem is that only a small fraction of patients achieve CR in this situation, and we do not know who they are going to be at time of relapse,” he told this news organization.

He agreed that “given robust randomized trials showing overall survival benefit of CAR-T compared to auto-HCT in patients with high risk relapsed DLBCL, CAR-T treatment should remain the current standard.

“However, these current results help to confirm the strategy for management of low- risk (late) relapses and indicate that auto-HCT still has a place for these patients if they achieve CR with salvage therapy.”

Dr. Shadman reported relationships with ADC therapeutics, Bristol Myers Squibb, Genmab, Lilly, Vincerx, Kite (Gilead), Janssen, Fate Therapeutics, MorphoSys/Incyte, AstraZeneca, BeiGene, Pharmacyclics, Mustang Bio, AbbVie, Genentech, MEI Pharma, Regeneron, and TG Therapeutics. Dr. Friedberg had no disclosures to report.

Patients with relapsed diffuse large B cell lymphoma (DLBCL) who achieve a complete remission from interim chemotherapy while awaiting secondary chimeric antigen receptor (CAR) T cell therapy show significantly better outcomes if they then receive conventional autologous stem cell transplantation (auto-HCT), compared with CAR T therapy.

“In patients with relapsed DLBCL in a complete remission, treatment with auto-HCT is associated with a lower rate of relapse/progression, and a longer progression-free survival [versus CAR T therapy],” said first author Mazyar Shadman, MD, MPH, of the Division of Medical Oncology, University of Washington, Seattle.

“The data support utilization of auto-HCT in patients with relapsed LBCL achieving a complete response,” he said.

The findings were presented at the annual meeting of the American Society of Hematology in San Diego.

While approximately 60% of patients with DLBCL are successfully treated after an initial anthracycline-based and rituximab-containing chemotherapy regimen, those who do not improve have poorer outcomes, and CAR T-cell therapy has emerged as the standard of care for those patients, based on results from the ZUMA-7 and TRANSFORM clinical trials.

But with delays in accessing CAR T quite common, patients will often receive interim chemotherapy while awaiting referral to a CAR T center, and occasionally, usually unexpectedly, some will achieve a partial or complete response.

In previous research involving patients who achieved a partial remission in such interim cases, Dr. Shadman and colleagues demonstrated that auto-HCT had favorable outcomes, compared with those who received CAR T therapy.

For the new retrospective, real-world analysis, the authors compared outcomes with the treatment options among 360 patients between the ages of 18 and 75 who were enrolled in the Center for International Blood & Marrow Transplant Research registry and had received auto-HCT or CAR T therapy after achieving a complete remission following salvage chemotherapy.

Of those receiving CAR-T cell therapy, most (53.2%) received tisagenlecleucel (tisa-cel), followed by axicabtagene ciloleucel (axi-cel, 45.6%) and lisocabtagene maraleucel (liso-cel, 1.3%), between 2018 and 2021, while 281 patients were treated with auto-HCT between 2015 and 2021.

With a median follow-up of 49.7 months (range 3.0-94.4) for auto-HCT and 24.7 months (range 3.3-49.4) for CAR-T, a univariate analysis showed the rate of 2-year progression free survival was 66.2% in the auto-HCT group and 47.8% in the CAR T group (P < .001).

The results also favored auto-HCT for 2-year progression/relapse, with a cumulative incidence of 27.8% with auto-HCT versus 48% with CAR T (P < .001), and the 2-year overall survival was higher with auto-HCT (78.9% vs. 65.6%; P = .037).

After adjustment in multivariable analysis adjusting for relevant clinical variables, auto-HCT versus CAR T remained associated with a lower risk of relapse or progression (HR 2.18; P < .0001) and an improved progression-free survival (HR 1.83; P = .0011), with no significant differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).

Deaths occurred among 85 patients in the auto-HCT group and 25 in the CAR T cohort, with lymphoma being the main cause of death in both groups (60% and 68%, respectively).

While 37 (13.2%) of auto-HCT patients later received subsequent CAR-T therapy, no patients receiving CAR-T had subsequent auto-HCT.

There were no differences between the CAR-T and auto-HST groups in rates of 2-year treatment-related mortality (4.1% vs. 5.9%; P = .673).

A subanalysis of those who had treatment failure at 12 months, (CAR-T = 57 and auto-HCT = 163) showed that those receiving CAR-T therapy had a higher 2-year relapse rate (46.3% vs. 25%; P < .001); an inferior 2-year progression-free survival rate (48.4% vs. 68.2%; P = .001) compared with auto-HCT, while there were no significant differences between the groups in terms of 2-year overall survival or treatment-related mortality.

After a multivariable analysis adjusting for relevant clinical factors, CAR-T therapy remained associated with higher risk of relapse (HR 2.18; P < .0001) and an inferior progression-free survival (HR 1.83; P = .0011) compared with auto-HCT, with no differences in the risk of treatment-related mortality (HR 0.59; P = .36) or overall survival (HR 1.44; P = .12).

“These results are consistent with our previously reported findings, indicating higher efficacy of auto-HCT compared with CAR T in patients with partial remission,” Dr. Shadman said.

In addition to the study’s being a retrospective analysis, limitations include that more than half of patients in the CAR T cohort received tisa-cel, which could have lower efficacy compared with other approved CAR T therapies, Dr. Shadman noted.

“A repeat analysis by including more patients treated with axi-cel or liso-cel may address this issue in the future,” he said.

Discussing the results in a press briefing, Dr. Shadman underscored that “there is no question the choice of therapy for these DLBCL patients with primary refractory disease should be second-line CAR T therapy — we are not suggesting that those patients should be sent for auto-HCT,” he said.

“What we are saying is, in real-world practice ... patients may need chemotherapy treatment in the interim (awaiting CAR T treatment), and we don’t expect these patients to respond to those cycles because they have already shown us that they don’t do well with chemotherapy — however some do respond and can go into complete remission.”

The question then becomes whether patients at that point will fare better with CAR T or auto-HCT, and the results indicate that “auto-HCT gives those patients a pretty solid remission that looks better than [that with] CAR T therapy.”

Dr. Shadman noted that the results serve to inform or confirm key clinical practices, including “in patients with late relapses, after 12 months, auto-HCT should remain the standard of care.

“In patients with primary refractory disease or early relapse, CAR T should be the goal of therapy and improving access to CAR T should remain a priority.

“In the subset of patients who achieve a CR with interim treatment, a discussion about the possibility of utilizing auto-HCT seems reasonable and can provide another curative option for some patients while keeping CAR-T as a backup treatment plan in case of auto-HCT failure.”

Commenting on the study, Jonathan W. Friedberg, MD, the Samuel Durand Professor of Medicine and director of the Wilmot Cancer Institute, University of Rochester, New York, said, “these findings confirm utility of auto-HCT in patients who achieve a CR.”

However, “the problem is that only a small fraction of patients achieve CR in this situation, and we do not know who they are going to be at time of relapse,” he told this news organization.

He agreed that “given robust randomized trials showing overall survival benefit of CAR-T compared to auto-HCT in patients with high risk relapsed DLBCL, CAR-T treatment should remain the current standard.

“However, these current results help to confirm the strategy for management of low- risk (late) relapses and indicate that auto-HCT still has a place for these patients if they achieve CR with salvage therapy.”

Dr. Shadman reported relationships with ADC therapeutics, Bristol Myers Squibb, Genmab, Lilly, Vincerx, Kite (Gilead), Janssen, Fate Therapeutics, MorphoSys/Incyte, AstraZeneca, BeiGene, Pharmacyclics, Mustang Bio, AbbVie, Genentech, MEI Pharma, Regeneron, and TG Therapeutics. Dr. Friedberg had no disclosures to report.

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

fda_icon3_web_3.jpg

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

fda_icon3_web_3.jpg

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has granted accelerated approval to pirtobrutinib (Jaypirca; Eli Lilly and Company) for third-line or later treatment in adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who previously received a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.

fda_icon3_web_3.jpg

The agent was initially approved in January 2023 for patients with mantle cell lymphoma who had previously received a BTK inhibitor.

Like the mantle cell approval, the CLL/SLL approval was based on findings from the open-label, single-arm, phase 1/2 BRUIN study that included adults with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

The trial included 108 patients with either CLL or SLL. Overall, patients demonstrated an overall response rate of 72%, all of which were partial responses, and median duration of response of 12.2 months.

Before starting pirtobrutinib, 77% of patients with CLL or SLL had discontinued their last BTK inhibitor for refractory or progressive disease.

“Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of Jaypirca a meaningful advance and much-needed new treatment option for these patients,” William G. Wierda, MD, PhD, of the University of Texas MD Anderson Cancer Center, Houston, said in an Eli Lilly press release. 

Treatment during the study included the recommended dose of 200 mg given orally once daily until disease progression or unacceptable toxicity. Common adverse reactions that occurred in at least 20% of patients included fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. Grade 3 or 4 laboratory abnormalities occurring in more than 10% of patients included decreased neutrophil counts, anemia, and decreased platelet counts.

Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information for pirtobrutinib includes warnings about infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.

A version of this article first appeared on Medscape.com.

Key clinical point: Survivors of mantle cell lymphoma (MCL), particularly those treated with rituximab plus bendamustine (R-bendamustine), have an increased risk for secondary malignancies (SM).

Major finding: Patients with MCL vs lymphoma-free comparators had significantly higher rates of SM (adjusted hazard ratio [aHR] 1.6; 95% CI 1.4-1.8), with higher rates being observed across all primary treatment groups, ie, the Nordic-MCL2 protocol; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP); R-bendamustine; ibrutinib; lenalidomide; and R-CHOP/cytarabine groups. Treatment with R-bendamustine vs Nordic-MCL2 was independently associated with an increased risk for SM (aHR 2.0; 95% CI 1.3-3.2).

Study details: This population-based retrospective study included adult patients with MCL (n = 1452), each of whom was matched with ≤10 lymphoma-free comparators from the general population (n = 13,992).

Disclosures: This study was funded by the Swedish Cancer Society. I Glimelius and S Eloranta declared receiving research grants, contracts, or support for attending meetings from various sources, including the Swedish Cancer Society. The other authors declared no conflicts of interest.

Source: Abalo KD et al. Secondary malignancies among mantle cell lymphoma patients. Eur J Cancer. 2023;195:113403 (Oct 28). doi: 10.1016/j.ejca.2023.113403

Key clinical point: Survivors of mantle cell lymphoma (MCL), particularly those treated with rituximab plus bendamustine (R-bendamustine), have an increased risk for secondary malignancies (SM).

Major finding: Patients with MCL vs lymphoma-free comparators had significantly higher rates of SM (adjusted hazard ratio [aHR] 1.6; 95% CI 1.4-1.8), with higher rates being observed across all primary treatment groups, ie, the Nordic-MCL2 protocol; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP); R-bendamustine; ibrutinib; lenalidomide; and R-CHOP/cytarabine groups. Treatment with R-bendamustine vs Nordic-MCL2 was independently associated with an increased risk for SM (aHR 2.0; 95% CI 1.3-3.2).

Study details: This population-based retrospective study included adult patients with MCL (n = 1452), each of whom was matched with ≤10 lymphoma-free comparators from the general population (n = 13,992).

Disclosures: This study was funded by the Swedish Cancer Society. I Glimelius and S Eloranta declared receiving research grants, contracts, or support for attending meetings from various sources, including the Swedish Cancer Society. The other authors declared no conflicts of interest.

Source: Abalo KD et al. Secondary malignancies among mantle cell lymphoma patients. Eur J Cancer. 2023;195:113403 (Oct 28). doi: 10.1016/j.ejca.2023.113403

Key clinical point: Survivors of mantle cell lymphoma (MCL), particularly those treated with rituximab plus bendamustine (R-bendamustine), have an increased risk for secondary malignancies (SM).

Major finding: Patients with MCL vs lymphoma-free comparators had significantly higher rates of SM (adjusted hazard ratio [aHR] 1.6; 95% CI 1.4-1.8), with higher rates being observed across all primary treatment groups, ie, the Nordic-MCL2 protocol; rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP); R-bendamustine; ibrutinib; lenalidomide; and R-CHOP/cytarabine groups. Treatment with R-bendamustine vs Nordic-MCL2 was independently associated with an increased risk for SM (aHR 2.0; 95% CI 1.3-3.2).

Study details: This population-based retrospective study included adult patients with MCL (n = 1452), each of whom was matched with ≤10 lymphoma-free comparators from the general population (n = 13,992).

Disclosures: This study was funded by the Swedish Cancer Society. I Glimelius and S Eloranta declared receiving research grants, contracts, or support for attending meetings from various sources, including the Swedish Cancer Society. The other authors declared no conflicts of interest.

Source: Abalo KD et al. Secondary malignancies among mantle cell lymphoma patients. Eur J Cancer. 2023;195:113403 (Oct 28). doi: 10.1016/j.ejca.2023.113403

Key clinical point: The combination of tisagenlecleucel and time-limited ibrutinib improved outcomes and could be safely administered to patients with relapsed or refractory mantle cell lymphoma (r/r MCL), irrespective of prior covalent Bruton tyrosine kinase inhibitor (BTKi) exposure.

Major finding: At 4 months post infusion, the overall and complete response rates were 80% each. Patients with and without prior BTKi exposure had complete response rates of 90% and 70%, respectively. Grades 1-2 and grade 3 cytokine release syndrome rates were 55% and 20%, respectively.

Study details: This phase 2 study, TARMAC, included 20 patients having r/r MCL after ≥1 prior lines of therapy with (n = 10) or without (n = 10) a BTKi who were infused with tisagenlecleucel and commenced ibrutinib before leukapheresis and continued it for ≥6 months post infusion.

Disclosures: The study was sponsored by Peter MacCallum Cancer Centre, Australia. Several authors declared being members of the advisory committee, board of directors, or speakers’ bureau of or receiving honoraria or research funding from various sources.

Source: Minson AG et al. CAR T-cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: Phase II TARMAC study. Blood. 2023 (Oct 26). doi: 10.1182/blood.2023021306

Key clinical point: The combination of tisagenlecleucel and time-limited ibrutinib improved outcomes and could be safely administered to patients with relapsed or refractory mantle cell lymphoma (r/r MCL), irrespective of prior covalent Bruton tyrosine kinase inhibitor (BTKi) exposure.

Major finding: At 4 months post infusion, the overall and complete response rates were 80% each. Patients with and without prior BTKi exposure had complete response rates of 90% and 70%, respectively. Grades 1-2 and grade 3 cytokine release syndrome rates were 55% and 20%, respectively.

Study details: This phase 2 study, TARMAC, included 20 patients having r/r MCL after ≥1 prior lines of therapy with (n = 10) or without (n = 10) a BTKi who were infused with tisagenlecleucel and commenced ibrutinib before leukapheresis and continued it for ≥6 months post infusion.

Disclosures: The study was sponsored by Peter MacCallum Cancer Centre, Australia. Several authors declared being members of the advisory committee, board of directors, or speakers’ bureau of or receiving honoraria or research funding from various sources.

Source: Minson AG et al. CAR T-cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: Phase II TARMAC study. Blood. 2023 (Oct 26). doi: 10.1182/blood.2023021306

Key clinical point: The combination of tisagenlecleucel and time-limited ibrutinib improved outcomes and could be safely administered to patients with relapsed or refractory mantle cell lymphoma (r/r MCL), irrespective of prior covalent Bruton tyrosine kinase inhibitor (BTKi) exposure.

Major finding: At 4 months post infusion, the overall and complete response rates were 80% each. Patients with and without prior BTKi exposure had complete response rates of 90% and 70%, respectively. Grades 1-2 and grade 3 cytokine release syndrome rates were 55% and 20%, respectively.

Study details: This phase 2 study, TARMAC, included 20 patients having r/r MCL after ≥1 prior lines of therapy with (n = 10) or without (n = 10) a BTKi who were infused with tisagenlecleucel and commenced ibrutinib before leukapheresis and continued it for ≥6 months post infusion.

Disclosures: The study was sponsored by Peter MacCallum Cancer Centre, Australia. Several authors declared being members of the advisory committee, board of directors, or speakers’ bureau of or receiving honoraria or research funding from various sources.

Source: Minson AG et al. CAR T-cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: Phase II TARMAC study. Blood. 2023 (Oct 26). doi: 10.1182/blood.2023021306

Key clinical point: Compared with tisagenlecleucel, axicabtagene ciloleucel (axi-cel) was associated with improved treatment outcomes but increased the risk for grade ≥ 3 neurologic events in patients with relapsed or refractory large B-cell lymphoma (LBCL) in real-world settings.

Major finding: Axi-cel vs tisagenlecleucel improved the overall survival (adjusted hazard ratio [aHR] 0.60; 95% CI 0.47-0.77), progression-free survival (aHR 0.67; 95% CI 0.57-0.78), and overall response rate (odds ratio 2.05; 95% CI 1.76-2.40). However, it was associated with a higher incidence of grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (odds ratio 3.95; 95% CI 3.05-5.11).

Study details: This comparative meta-analysis of 14 real-world cohorts included patients with relapsed or refractory LBCL who received axi-cel (n = 2432) or tisagenlecleucel (n = 1514) chimeric antigen receptor T-cell therapy.

Disclosures: This study was funded by Kite, a Gilead Company. Six authors declared being employees of or holding leadership positions and stocks in Kite or Gilead. Several authors reported receiving honoraria, travel fees, research funding, etc., from various sources, including Kite.

Source: Jacobson CA et al. Real-world outcomes with CAR T-cell therapies in large B-cell lymphoma: A systematic review and meta-analysis. Transplant Cell Ther. 2023 (Oct 25). doi: 10.1016/j.jtct.2023.10.017

Key clinical point: Compared with tisagenlecleucel, axicabtagene ciloleucel (axi-cel) was associated with improved treatment outcomes but increased the risk for grade ≥ 3 neurologic events in patients with relapsed or refractory large B-cell lymphoma (LBCL) in real-world settings.

Major finding: Axi-cel vs tisagenlecleucel improved the overall survival (adjusted hazard ratio [aHR] 0.60; 95% CI 0.47-0.77), progression-free survival (aHR 0.67; 95% CI 0.57-0.78), and overall response rate (odds ratio 2.05; 95% CI 1.76-2.40). However, it was associated with a higher incidence of grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (odds ratio 3.95; 95% CI 3.05-5.11).

Study details: This comparative meta-analysis of 14 real-world cohorts included patients with relapsed or refractory LBCL who received axi-cel (n = 2432) or tisagenlecleucel (n = 1514) chimeric antigen receptor T-cell therapy.

Disclosures: This study was funded by Kite, a Gilead Company. Six authors declared being employees of or holding leadership positions and stocks in Kite or Gilead. Several authors reported receiving honoraria, travel fees, research funding, etc., from various sources, including Kite.

Source: Jacobson CA et al. Real-world outcomes with CAR T-cell therapies in large B-cell lymphoma: A systematic review and meta-analysis. Transplant Cell Ther. 2023 (Oct 25). doi: 10.1016/j.jtct.2023.10.017

Key clinical point: Compared with tisagenlecleucel, axicabtagene ciloleucel (axi-cel) was associated with improved treatment outcomes but increased the risk for grade ≥ 3 neurologic events in patients with relapsed or refractory large B-cell lymphoma (LBCL) in real-world settings.

Major finding: Axi-cel vs tisagenlecleucel improved the overall survival (adjusted hazard ratio [aHR] 0.60; 95% CI 0.47-0.77), progression-free survival (aHR 0.67; 95% CI 0.57-0.78), and overall response rate (odds ratio 2.05; 95% CI 1.76-2.40). However, it was associated with a higher incidence of grade ≥ 3 immune effector cell-associated neurotoxicity syndrome (odds ratio 3.95; 95% CI 3.05-5.11).

Study details: This comparative meta-analysis of 14 real-world cohorts included patients with relapsed or refractory LBCL who received axi-cel (n = 2432) or tisagenlecleucel (n = 1514) chimeric antigen receptor T-cell therapy.

Disclosures: This study was funded by Kite, a Gilead Company. Six authors declared being employees of or holding leadership positions and stocks in Kite or Gilead. Several authors reported receiving honoraria, travel fees, research funding, etc., from various sources, including Kite.

Source: Jacobson CA et al. Real-world outcomes with CAR T-cell therapies in large B-cell lymphoma: A systematic review and meta-analysis. Transplant Cell Ther. 2023 (Oct 25). doi: 10.1016/j.jtct.2023.10.017

Key clinical point: Total metabolic tumor volume (MTV) is an independent prognostic factor for treatment response and survival in patients receiving loncastuximab tesirine for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with ≥2 prior systemic therapy lines.

Major finding: An MTV ≥ 96 mL was significantly associated with failure to achieve a complete metabolic response (adjusted odds ratio 5.42; P  =  .002). Patients with an MTV ≥ 96 mL vs < 96 mL had shorter progression-free survival (adjusted hazard ratio [aHR] 2.68; P  =  .002) and overall survival (aHR 3.09; P < .0001).L

Study details: This post hoc analysis reviewed the screening PET/CT scans of 138 patients with relapsed or refractory DLBCL treated with ≥2 prior systemic therapy lines who received loncastuximab tesirine in LOTIS-2.

Disclosures: This study was supported by ADC Therapeutics, SA, and the Sylvester Comprehensive Cancer Center, Miami. Some authors declared serving as consultants, advisors, etc., for or receiving research funding or honoraria from ADC Therapeutics and others. J Radford declared owing stocks in ADC Therapeutics.

Source: Alderuccio JP et al. PET/CT-biomarkers enable risk stratification of patients with relapsed/refractory diffuse large B-cell lymphoma enrolled in the LOTIS-2 clinical trial. Clin Cancer Res. 2023 (Oct 19). doi: 10.1158/1078-0432.CCR-23-1561

Key clinical point: Total metabolic tumor volume (MTV) is an independent prognostic factor for treatment response and survival in patients receiving loncastuximab tesirine for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with ≥2 prior systemic therapy lines.

Major finding: An MTV ≥ 96 mL was significantly associated with failure to achieve a complete metabolic response (adjusted odds ratio 5.42; P  =  .002). Patients with an MTV ≥ 96 mL vs < 96 mL had shorter progression-free survival (adjusted hazard ratio [aHR] 2.68; P  =  .002) and overall survival (aHR 3.09; P < .0001).L

Study details: This post hoc analysis reviewed the screening PET/CT scans of 138 patients with relapsed or refractory DLBCL treated with ≥2 prior systemic therapy lines who received loncastuximab tesirine in LOTIS-2.

Disclosures: This study was supported by ADC Therapeutics, SA, and the Sylvester Comprehensive Cancer Center, Miami. Some authors declared serving as consultants, advisors, etc., for or receiving research funding or honoraria from ADC Therapeutics and others. J Radford declared owing stocks in ADC Therapeutics.

Source: Alderuccio JP et al. PET/CT-biomarkers enable risk stratification of patients with relapsed/refractory diffuse large B-cell lymphoma enrolled in the LOTIS-2 clinical trial. Clin Cancer Res. 2023 (Oct 19). doi: 10.1158/1078-0432.CCR-23-1561

Key clinical point: Total metabolic tumor volume (MTV) is an independent prognostic factor for treatment response and survival in patients receiving loncastuximab tesirine for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) treated with ≥2 prior systemic therapy lines.

Major finding: An MTV ≥ 96 mL was significantly associated with failure to achieve a complete metabolic response (adjusted odds ratio 5.42; P  =  .002). Patients with an MTV ≥ 96 mL vs < 96 mL had shorter progression-free survival (adjusted hazard ratio [aHR] 2.68; P  =  .002) and overall survival (aHR 3.09; P < .0001).L

Study details: This post hoc analysis reviewed the screening PET/CT scans of 138 patients with relapsed or refractory DLBCL treated with ≥2 prior systemic therapy lines who received loncastuximab tesirine in LOTIS-2.

Disclosures: This study was supported by ADC Therapeutics, SA, and the Sylvester Comprehensive Cancer Center, Miami. Some authors declared serving as consultants, advisors, etc., for or receiving research funding or honoraria from ADC Therapeutics and others. J Radford declared owing stocks in ADC Therapeutics.

Source: Alderuccio JP et al. PET/CT-biomarkers enable risk stratification of patients with relapsed/refractory diffuse large B-cell lymphoma enrolled in the LOTIS-2 clinical trial. Clin Cancer Res. 2023 (Oct 19). doi: 10.1158/1078-0432.CCR-23-1561

Key clinical point: The outcomes of autologous stem cell transplantation (ASCT) are not superior to those of anti-CD20 radioimmunotherapy, which offers a less toxic consolidation approach, in patients with relapsed or refractory (R/R) follicular lymphoma (FL) receiving rituximab-based induction and maintenance.

Major finding: At a 77-month median follow-up, both treatment groups had estimated 3-year progression-free survival rates of 62% (hazard ratio [HR] 1.11; P  =  .6662) and similar 3-year overall survival (HR 0.94; P  =  .8588). ASCT vs radioimmunotherapy led to higher rates of grade ≥ 3 hematological toxicity and grade ≥ 3 neutropenia (both P < .001).

Study details: This phase 3 FLAZ12 trial included 159 patients with R/R FL after ≤2 chemotherapy lines (≥1 lines containing rituximab) who received rituximab-based induction chemoimmunotherapy, with those showing a partial or complete response being randomized 1:1 to receive ASCT or radioimmunotherapy, both followed by rituximab maintenance.

Disclosures: This study was funded by the Agenzia Italiana del Farmaco (AIFA) and Fondazione Italiana Linfomi. Some authors declared receiving honoraria or research funding from AIFA and others.

Source: Ladetto M, Tavarozzi  R, et al. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapse/refractory follicular lymphoma: A Fondazione Italiana Linfomi multicenter, randomized, phase 3 trial. Ann Oncol. 2023 (Nov 1). doi: 10.1016/j.annonc.2023.10.095

Key clinical point: The outcomes of autologous stem cell transplantation (ASCT) are not superior to those of anti-CD20 radioimmunotherapy, which offers a less toxic consolidation approach, in patients with relapsed or refractory (R/R) follicular lymphoma (FL) receiving rituximab-based induction and maintenance.

Major finding: At a 77-month median follow-up, both treatment groups had estimated 3-year progression-free survival rates of 62% (hazard ratio [HR] 1.11; P  =  .6662) and similar 3-year overall survival (HR 0.94; P  =  .8588). ASCT vs radioimmunotherapy led to higher rates of grade ≥ 3 hematological toxicity and grade ≥ 3 neutropenia (both P < .001).

Study details: This phase 3 FLAZ12 trial included 159 patients with R/R FL after ≤2 chemotherapy lines (≥1 lines containing rituximab) who received rituximab-based induction chemoimmunotherapy, with those showing a partial or complete response being randomized 1:1 to receive ASCT or radioimmunotherapy, both followed by rituximab maintenance.

Disclosures: This study was funded by the Agenzia Italiana del Farmaco (AIFA) and Fondazione Italiana Linfomi. Some authors declared receiving honoraria or research funding from AIFA and others.

Source: Ladetto M, Tavarozzi  R, et al. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapse/refractory follicular lymphoma: A Fondazione Italiana Linfomi multicenter, randomized, phase 3 trial. Ann Oncol. 2023 (Nov 1). doi: 10.1016/j.annonc.2023.10.095

Key clinical point: The outcomes of autologous stem cell transplantation (ASCT) are not superior to those of anti-CD20 radioimmunotherapy, which offers a less toxic consolidation approach, in patients with relapsed or refractory (R/R) follicular lymphoma (FL) receiving rituximab-based induction and maintenance.

Major finding: At a 77-month median follow-up, both treatment groups had estimated 3-year progression-free survival rates of 62% (hazard ratio [HR] 1.11; P  =  .6662) and similar 3-year overall survival (HR 0.94; P  =  .8588). ASCT vs radioimmunotherapy led to higher rates of grade ≥ 3 hematological toxicity and grade ≥ 3 neutropenia (both P < .001).

Study details: This phase 3 FLAZ12 trial included 159 patients with R/R FL after ≤2 chemotherapy lines (≥1 lines containing rituximab) who received rituximab-based induction chemoimmunotherapy, with those showing a partial or complete response being randomized 1:1 to receive ASCT or radioimmunotherapy, both followed by rituximab maintenance.

Disclosures: This study was funded by the Agenzia Italiana del Farmaco (AIFA) and Fondazione Italiana Linfomi. Some authors declared receiving honoraria or research funding from AIFA and others.

Source: Ladetto M, Tavarozzi  R, et al. Radioimmunotherapy versus autologous hematopoietic stem cell transplantation in relapse/refractory follicular lymphoma: A Fondazione Italiana Linfomi multicenter, randomized, phase 3 trial. Ann Oncol. 2023 (Nov 1). doi: 10.1016/j.annonc.2023.10.095

Key clinical point: TP53 mutations detected by clinical laboratory mutation analysis (CLMA) can independently predict poor outcomes in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) treated with first-line immunochemotherapy.

Major finding: TP53 mutations significantly predicted disease progression at 2 years (adjusted hazard ratio 2.3; P  =  .03). Patients with vs without TP53 mutations had significantly lower overall response (71% vs 90%; P  =  .009), complete response (55% vs 77%, P  =  .01), estimated 2-year progression-free survival (57% vs 77%; P  =  .006), and estimated 2-year overall survival (70% vs 91%; P  =  .001) rates.

Study details: This study included 122 patients with newly diagnosed DLBCL or HGBL receiving first-line immunochemotherapy whose diagnostic biopsies underwent CLMA, of whom 42 patients had TP53 mutations.

Disclosures: This study did not disclose any funding source. All authors, except A Bagg, declared receiving honoraria, travel grants, or research funding from or having other ties with various sources.

Source: Landsburg DJ et al. TP53 mutations predict for poor outcomes in patients with newly-diagnosed aggressive B cell lymphomas in the current era. Blood Adv. 2023 (Oct 18). doi: 10.1182/bloodadvances.2023011384

Key clinical point: TP53 mutations detected by clinical laboratory mutation analysis (CLMA) can independently predict poor outcomes in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) treated with first-line immunochemotherapy.

Major finding: TP53 mutations significantly predicted disease progression at 2 years (adjusted hazard ratio 2.3; P  =  .03). Patients with vs without TP53 mutations had significantly lower overall response (71% vs 90%; P  =  .009), complete response (55% vs 77%, P  =  .01), estimated 2-year progression-free survival (57% vs 77%; P  =  .006), and estimated 2-year overall survival (70% vs 91%; P  =  .001) rates.

Study details: This study included 122 patients with newly diagnosed DLBCL or HGBL receiving first-line immunochemotherapy whose diagnostic biopsies underwent CLMA, of whom 42 patients had TP53 mutations.

Disclosures: This study did not disclose any funding source. All authors, except A Bagg, declared receiving honoraria, travel grants, or research funding from or having other ties with various sources.

Source: Landsburg DJ et al. TP53 mutations predict for poor outcomes in patients with newly-diagnosed aggressive B cell lymphomas in the current era. Blood Adv. 2023 (Oct 18). doi: 10.1182/bloodadvances.2023011384

Key clinical point: TP53 mutations detected by clinical laboratory mutation analysis (CLMA) can independently predict poor outcomes in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) or high-grade B cell lymphoma (HGBL) treated with first-line immunochemotherapy.

Major finding: TP53 mutations significantly predicted disease progression at 2 years (adjusted hazard ratio 2.3; P  =  .03). Patients with vs without TP53 mutations had significantly lower overall response (71% vs 90%; P  =  .009), complete response (55% vs 77%, P  =  .01), estimated 2-year progression-free survival (57% vs 77%; P  =  .006), and estimated 2-year overall survival (70% vs 91%; P  =  .001) rates.

Study details: This study included 122 patients with newly diagnosed DLBCL or HGBL receiving first-line immunochemotherapy whose diagnostic biopsies underwent CLMA, of whom 42 patients had TP53 mutations.

Disclosures: This study did not disclose any funding source. All authors, except A Bagg, declared receiving honoraria, travel grants, or research funding from or having other ties with various sources.

Source: Landsburg DJ et al. TP53 mutations predict for poor outcomes in patients with newly-diagnosed aggressive B cell lymphomas in the current era. Blood Adv. 2023 (Oct 18). doi: 10.1182/bloodadvances.2023011384