B-Cell Lymphoma ICYMI

Key clinical point: Time to progression of disease (POD), defined as the time between first-line rituximab‐based therapy initiation and disease progression before second-line Bruton tyrosine kinase inhibitor (BTKi) therapy initiation, is associated with survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL) receiving second-line BTKi therapy.

Major finding: After initiating second-line BTKi therapy, patients with POD within vs after 24 months of first-line therapy had significantly shorter median progression‐free survival (0.45 vs 2.3 years; P < .001) and overall survival (0.9 vs 5.5 years; P < .001).

Study details: This multicenter retrospective observational study included 360 adult patients with relapsed or refractory MCL who initiated second-line BTKi therapy after first-line rituximab-based therapy.

Disclosures: No information on the source of funding was provided. Some authors declared serving as consultants or advisors and receiving research funding, speaker fees, or honoraria from various sources.

Source: Villa D et al. Time to progression of disease and outcomes with second-line BTK inhibitors in relapsed/refractory mantle cell lymphoma. Blood Adv. 2023 (Jun 12). Doi: 10.1182/bloodadvances.2023009804

Key clinical point: Time to progression of disease (POD), defined as the time between first-line rituximab‐based therapy initiation and disease progression before second-line Bruton tyrosine kinase inhibitor (BTKi) therapy initiation, is associated with survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL) receiving second-line BTKi therapy.

Major finding: After initiating second-line BTKi therapy, patients with POD within vs after 24 months of first-line therapy had significantly shorter median progression‐free survival (0.45 vs 2.3 years; P < .001) and overall survival (0.9 vs 5.5 years; P < .001).

Study details: This multicenter retrospective observational study included 360 adult patients with relapsed or refractory MCL who initiated second-line BTKi therapy after first-line rituximab-based therapy.

Disclosures: No information on the source of funding was provided. Some authors declared serving as consultants or advisors and receiving research funding, speaker fees, or honoraria from various sources.

Source: Villa D et al. Time to progression of disease and outcomes with second-line BTK inhibitors in relapsed/refractory mantle cell lymphoma. Blood Adv. 2023 (Jun 12). Doi: 10.1182/bloodadvances.2023009804

Key clinical point: Time to progression of disease (POD), defined as the time between first-line rituximab‐based therapy initiation and disease progression before second-line Bruton tyrosine kinase inhibitor (BTKi) therapy initiation, is associated with survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL) receiving second-line BTKi therapy.

Major finding: After initiating second-line BTKi therapy, patients with POD within vs after 24 months of first-line therapy had significantly shorter median progression‐free survival (0.45 vs 2.3 years; P < .001) and overall survival (0.9 vs 5.5 years; P < .001).

Study details: This multicenter retrospective observational study included 360 adult patients with relapsed or refractory MCL who initiated second-line BTKi therapy after first-line rituximab-based therapy.

Disclosures: No information on the source of funding was provided. Some authors declared serving as consultants or advisors and receiving research funding, speaker fees, or honoraria from various sources.

Source: Villa D et al. Time to progression of disease and outcomes with second-line BTK inhibitors in relapsed/refractory mantle cell lymphoma. Blood Adv. 2023 (Jun 12). Doi: 10.1182/bloodadvances.2023009804

Key clinical point: The noncovalent Bruton’s tyrosine kinase inhibitor (BTKi) pirtobrutinib was efficacious in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously received BTKi therapy.

Major finding: An overall response was achieved by 73.3% (95% CI 67.3%-78.7%) of patients previously treated with BTKi therapy and by 82.2% (95% CI 76.8%-86.7%) of patients when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. Only 2.8% of patients discontinued pirtobrutinib permanently due to treatment-related adverse events.

Study details: Findings are from the phase 1-2 BRUIN trial including 317 patients with relapsed or refractory CLL or SLL who received pirtobrutinib, of which 247 had previously received ≥1 BTK inhibitor.

Disclosures: This study was supported by Loxo Oncology, a subsidiary of Eli Lilly. Some authors, including the lead author, declared serving as consultants or speakers for or receiving advisory board honoraria, travel support, or research funding from Loxo/Lilly. Seven authors declared being employees or stockholders of Loxo/Lilly.

Source: Mato AR et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389:33-44 (Jul 6). Doi: 10.1056/NEJMoa2300696

Key clinical point: The noncovalent Bruton’s tyrosine kinase inhibitor (BTKi) pirtobrutinib was efficacious in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously received BTKi therapy.

Major finding: An overall response was achieved by 73.3% (95% CI 67.3%-78.7%) of patients previously treated with BTKi therapy and by 82.2% (95% CI 76.8%-86.7%) of patients when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. Only 2.8% of patients discontinued pirtobrutinib permanently due to treatment-related adverse events.

Study details: Findings are from the phase 1-2 BRUIN trial including 317 patients with relapsed or refractory CLL or SLL who received pirtobrutinib, of which 247 had previously received ≥1 BTK inhibitor.

Disclosures: This study was supported by Loxo Oncology, a subsidiary of Eli Lilly. Some authors, including the lead author, declared serving as consultants or speakers for or receiving advisory board honoraria, travel support, or research funding from Loxo/Lilly. Seven authors declared being employees or stockholders of Loxo/Lilly.

Source: Mato AR et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389:33-44 (Jul 6). Doi: 10.1056/NEJMoa2300696

Key clinical point: The noncovalent Bruton’s tyrosine kinase inhibitor (BTKi) pirtobrutinib was efficacious in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who had previously received BTKi therapy.

Major finding: An overall response was achieved by 73.3% (95% CI 67.3%-78.7%) of patients previously treated with BTKi therapy and by 82.2% (95% CI 76.8%-86.7%) of patients when partial response with lymphocytosis was included. At a 19.4-month median follow-up, the median progression-free survival was 19.6 (95% CI 16.9-22.1) months. Only 2.8% of patients discontinued pirtobrutinib permanently due to treatment-related adverse events.

Study details: Findings are from the phase 1-2 BRUIN trial including 317 patients with relapsed or refractory CLL or SLL who received pirtobrutinib, of which 247 had previously received ≥1 BTK inhibitor.

Disclosures: This study was supported by Loxo Oncology, a subsidiary of Eli Lilly. Some authors, including the lead author, declared serving as consultants or speakers for or receiving advisory board honoraria, travel support, or research funding from Loxo/Lilly. Seven authors declared being employees or stockholders of Loxo/Lilly.

Source: Mato AR et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389:33-44 (Jul 6). Doi: 10.1056/NEJMoa2300696

Interim follow-up data from the A041702 phase-3 clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (June 2-6) indicates that the addition of venetoclax (V) to ibrutinib + obinutuzumab (IO) to treat chronic lymphocytic leukemia (CLL) does not increase short- or medium-term progression-free survival (PFS) in older patients. The difference in PFS between the IVO arm, 85%, versus 87% in the IO arm was statistically insignificant.

“Due to the early read-out and the futility boundaries being crossed, long-term follow-up will be critical to understand if there are any long-term benefits to IVO,” said study principal investigator Jennifer A. Woyach MD, professor in the division of hematology at The Ohio State University Comprehensive Care Center (OSUCCC – The James) in Columbus.

The Ohio State University Comprehensive Care Center

The 14-month follow-up data includes results from 465 CLL patients aged 65+ (median age 74 years, 67.5% male) who were treatment naive. The IO and IVO arms had 232 and 233 participants respectively, patients across both arms had Eastern Cooperative Oncology Group scores of 0-1 (97%), occurrence of Del (17p) was 13%, and a Rai stage status of III/IV was 55%, slightly more patients in the IO arm had unmutated IGHV 55% vs. 47% in the IVO arm. Researchers noted that, as expected, patients in the IVO group had a greater occurrence of hematologic adverse events graded at 3 or above, 61% VS 48% in the IO arm, P =.006.

The trial was spurred by the fact that many CLL patients on IO therapy must remain on treatment indefinitely, and an earlier phase II trial suggested that IVO therapy could lead to deep remission and therapy discontinuation.

Looking at the complete response (CR) rates and undetectable minimal residual disease (uMRD) rates across both arms suggested that there may be some hope that IVO could help CLL patients achieve deep remissions and discontinue therapy. Patients in the IVO arm had a CR of 68.5% and uMRD of 86.8% while only 31.3% of those in the IO arm had a CR and 33.3% achieved uMRD status.

“Despite the impressive CR and uMRD results, this study demonstrates that IVO is not superior to IO in terms of progression-free survival. However, because many patients in the IVO arm have discontinued treatment while those in the IO arm remain on ibrutinib, we think that it will be very important to continue to follow these patients long term, to see if there are advantages to this time limited therapy, especially in terms of toxicity, that we cannot appreciate with this follow-up,” said Dr. Woyach.

The Alliance for Clinical Trials in Oncology cooperative group, including OSUCCC James, is currently working to design the next frontline CLL study for older patients that builds on this work.

Dr. Woyach disclosed ties with Abbvie, AstraZeneca, Beigene, Genentech, Janssen, Loxo/Lilly, Merck, Newave, Pharmacyclics, and Schrodinger.

Interim follow-up data from the A041702 phase-3 clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (June 2-6) indicates that the addition of venetoclax (V) to ibrutinib + obinutuzumab (IO) to treat chronic lymphocytic leukemia (CLL) does not increase short- or medium-term progression-free survival (PFS) in older patients. The difference in PFS between the IVO arm, 85%, versus 87% in the IO arm was statistically insignificant.

“Due to the early read-out and the futility boundaries being crossed, long-term follow-up will be critical to understand if there are any long-term benefits to IVO,” said study principal investigator Jennifer A. Woyach MD, professor in the division of hematology at The Ohio State University Comprehensive Care Center (OSUCCC – The James) in Columbus.

The Ohio State University Comprehensive Care Center

The 14-month follow-up data includes results from 465 CLL patients aged 65+ (median age 74 years, 67.5% male) who were treatment naive. The IO and IVO arms had 232 and 233 participants respectively, patients across both arms had Eastern Cooperative Oncology Group scores of 0-1 (97%), occurrence of Del (17p) was 13%, and a Rai stage status of III/IV was 55%, slightly more patients in the IO arm had unmutated IGHV 55% vs. 47% in the IVO arm. Researchers noted that, as expected, patients in the IVO group had a greater occurrence of hematologic adverse events graded at 3 or above, 61% VS 48% in the IO arm, P =.006.

The trial was spurred by the fact that many CLL patients on IO therapy must remain on treatment indefinitely, and an earlier phase II trial suggested that IVO therapy could lead to deep remission and therapy discontinuation.

Looking at the complete response (CR) rates and undetectable minimal residual disease (uMRD) rates across both arms suggested that there may be some hope that IVO could help CLL patients achieve deep remissions and discontinue therapy. Patients in the IVO arm had a CR of 68.5% and uMRD of 86.8% while only 31.3% of those in the IO arm had a CR and 33.3% achieved uMRD status.

“Despite the impressive CR and uMRD results, this study demonstrates that IVO is not superior to IO in terms of progression-free survival. However, because many patients in the IVO arm have discontinued treatment while those in the IO arm remain on ibrutinib, we think that it will be very important to continue to follow these patients long term, to see if there are advantages to this time limited therapy, especially in terms of toxicity, that we cannot appreciate with this follow-up,” said Dr. Woyach.

The Alliance for Clinical Trials in Oncology cooperative group, including OSUCCC James, is currently working to design the next frontline CLL study for older patients that builds on this work.

Dr. Woyach disclosed ties with Abbvie, AstraZeneca, Beigene, Genentech, Janssen, Loxo/Lilly, Merck, Newave, Pharmacyclics, and Schrodinger.

Interim follow-up data from the A041702 phase-3 clinical trial presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago (June 2-6) indicates that the addition of venetoclax (V) to ibrutinib + obinutuzumab (IO) to treat chronic lymphocytic leukemia (CLL) does not increase short- or medium-term progression-free survival (PFS) in older patients. The difference in PFS between the IVO arm, 85%, versus 87% in the IO arm was statistically insignificant.

“Due to the early read-out and the futility boundaries being crossed, long-term follow-up will be critical to understand if there are any long-term benefits to IVO,” said study principal investigator Jennifer A. Woyach MD, professor in the division of hematology at The Ohio State University Comprehensive Care Center (OSUCCC – The James) in Columbus.

The Ohio State University Comprehensive Care Center

The 14-month follow-up data includes results from 465 CLL patients aged 65+ (median age 74 years, 67.5% male) who were treatment naive. The IO and IVO arms had 232 and 233 participants respectively, patients across both arms had Eastern Cooperative Oncology Group scores of 0-1 (97%), occurrence of Del (17p) was 13%, and a Rai stage status of III/IV was 55%, slightly more patients in the IO arm had unmutated IGHV 55% vs. 47% in the IVO arm. Researchers noted that, as expected, patients in the IVO group had a greater occurrence of hematologic adverse events graded at 3 or above, 61% VS 48% in the IO arm, P =.006.

The trial was spurred by the fact that many CLL patients on IO therapy must remain on treatment indefinitely, and an earlier phase II trial suggested that IVO therapy could lead to deep remission and therapy discontinuation.

Looking at the complete response (CR) rates and undetectable minimal residual disease (uMRD) rates across both arms suggested that there may be some hope that IVO could help CLL patients achieve deep remissions and discontinue therapy. Patients in the IVO arm had a CR of 68.5% and uMRD of 86.8% while only 31.3% of those in the IO arm had a CR and 33.3% achieved uMRD status.

“Despite the impressive CR and uMRD results, this study demonstrates that IVO is not superior to IO in terms of progression-free survival. However, because many patients in the IVO arm have discontinued treatment while those in the IO arm remain on ibrutinib, we think that it will be very important to continue to follow these patients long term, to see if there are advantages to this time limited therapy, especially in terms of toxicity, that we cannot appreciate with this follow-up,” said Dr. Woyach.

The Alliance for Clinical Trials in Oncology cooperative group, including OSUCCC James, is currently working to design the next frontline CLL study for older patients that builds on this work.

Dr. Woyach disclosed ties with Abbvie, AstraZeneca, Beigene, Genentech, Janssen, Loxo/Lilly, Merck, Newave, Pharmacyclics, and Schrodinger.

Mantle cell lymphoma (MCL) is a rare and often heterogenous subtype of non-Hodgkin lymphoma (NHL). Though patients can experience prolonged remissions after frontline therapy, most patients ultimately relapse. Treatment of relapsed/refractory disease can be challenging, but there have recently been a growing number of therapeutic options in this setting. Covalent Bruton tyrosine kinase (BTK) inhibitors, for example, have demonstrated activity in patients with MCL and are approved by the US Food and Drug Administration (FDA) for relapsed/refractory disease. Chimeric antigen receptor (CAR) T-cell therapy is also an effective option for relapsed/refractory disease, though this is typically available only at select centers and is associated with toxicities, such as cytokine release syndrome and neurologic toxicity.

Recently, a novel BTK inhibitor, pirtobrutinib, has also been studied across NHL, including MCL (Wang et al) Pirtobrutinib is a selective, noncovalent BTK inhibitor with the ability to bind both the C481S-mutant and wild-type BTK. The multicenter, phase 1/2 BRUIN study included 90 patients with MCL who were previously treated with a covalent BTK inhibitor. Patients in the phase 1 portion of the study were treated with oral pirtobrutinib at a dose of 25-300 mg once daily, and patients in the phase 2 study were treated at the recommended dose of 200 mg once daily. The overall response rate was 57.8% (95% CI 46.9%-68.1%), with the complete response rate being 20.0%. At a median follow-up of 12 months, the median duration of response was 21.6 (95% CI 7.5 to not reached) months. Treatment-related adverse events that were grade 3 or higher were not frequent, with neutropenia (8.5%) being the most common. Of note, grade 3 or higher hemorrhage and atrial fibrillation, which can be seen with BTK inhibitors, were rare, occurring in 3.7% and 1.2% of patients, respectively. Based on the results of this study, pirtobrutinib has been approved by the FDA for patients with relapsed/refractory MCL after at least two prior lines of therapy, including a BTK inhibitor. This is an appealing oral option for patients with relapsed disease.

Options for patients with relapsed/refractory large B-cell lymphoma (LBCL) have also significantly increased in recent years. One of the most important advances in this disease has been the use of anti-CD19 CAR T-cell therapy. There are currently three FDA-approved options for patients with relapsed/refractory LBCL who have received at least two prior lines of therapy.^1-3 More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for the second line based on the results of the ZUMA-7 and TRANSFORM studies, respectively.^4,5

Longer follow-up of the ZUMA-7 trial continues to confirm the advantage of axi-cel over standard-care therapy for patients with primary refractory or early relapse of disease, now with evidence of an overall survival advantage (Westin et al). The ZUMA-7 trial included 359 adults with LBCL (refractory to or relapsed within 12 months of first-line treatment) who were randomly assigned to receive axi-cel (n = 180) or standard care (n = 179). At a median follow-up of 47.2 mo, patients receiving axi-cel vs standard care had a significantly longer median overall survival (not reached vs 31.1 mo; hazard ratio [HR] 0.73; P = .03) and an absolute improvement in overall survival (8.6 percentage points at 4 years). No new treatment-related deaths were reported since the primary event-free survival analysis. These data confirm that early use of axi-cel is preferred over standard-care therapy with high-dose chemotherapy and autologous stem cell transplantation.

Another important study that was recently published looked at the role of mental health on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (Kuczmarski et al). Though it is known that mental health disorders can decrease the quality of life of patients with cancer, there is limited information on the survival implications of these issues. A recent retrospective cohort study analyzed the data of 13,244 patients aged 67 years or older with DLBCL from the Surveillance, Epidemiology, and End Results (SEER)–Medicare registry, of which, 2094 patients had depression, anxiety, or both at the time of their DLBCL diagnosis. At a median follow-up of 2.0 years, patients with depression, anxiety, or both vs without any mental disorder had significantly lower 5-year overall survival rates (27.0% vs 37.4%; HR 1.37; 95% CI 1.29-1.44). They also found that those patients with preexisting depression vs without any mental disorder have the worst survival (23.4% vs 38.0%; HR 1.37; P < .0001). Though the mechanism accounting for decreased survival is not clear, the authors postulate that mental health disorders may lead to delays or interruptions in lymphoma-directed therapy. They also note the potential for increased barriers to care in patients with mental health disorders, which may result in nonadherence in this patient population. Regardless, these results highlight the importance of mental health screening and interventions in patients with DLBCL.

Additional References

1. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. doi: 10.1056/NEJMoa1707447
    
2. Schuster SJ, Bishop MR, Tam CS, et al; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. doi: 10.1056/NEJMoa1804980
    
3. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. doi: 10.1016/S0140-6736(20)31366-0
    
4. Locke FL, Miklos DB, Jacobson CA, et al; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133
5. Kamdar M, Solomon SR, Arnason J, et al; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6

Mantle cell lymphoma (MCL) is a rare and often heterogenous subtype of non-Hodgkin lymphoma (NHL). Though patients can experience prolonged remissions after frontline therapy, most patients ultimately relapse. Treatment of relapsed/refractory disease can be challenging, but there have recently been a growing number of therapeutic options in this setting. Covalent Bruton tyrosine kinase (BTK) inhibitors, for example, have demonstrated activity in patients with MCL and are approved by the US Food and Drug Administration (FDA) for relapsed/refractory disease. Chimeric antigen receptor (CAR) T-cell therapy is also an effective option for relapsed/refractory disease, though this is typically available only at select centers and is associated with toxicities, such as cytokine release syndrome and neurologic toxicity.

Recently, a novel BTK inhibitor, pirtobrutinib, has also been studied across NHL, including MCL (Wang et al) Pirtobrutinib is a selective, noncovalent BTK inhibitor with the ability to bind both the C481S-mutant and wild-type BTK. The multicenter, phase 1/2 BRUIN study included 90 patients with MCL who were previously treated with a covalent BTK inhibitor. Patients in the phase 1 portion of the study were treated with oral pirtobrutinib at a dose of 25-300 mg once daily, and patients in the phase 2 study were treated at the recommended dose of 200 mg once daily. The overall response rate was 57.8% (95% CI 46.9%-68.1%), with the complete response rate being 20.0%. At a median follow-up of 12 months, the median duration of response was 21.6 (95% CI 7.5 to not reached) months. Treatment-related adverse events that were grade 3 or higher were not frequent, with neutropenia (8.5%) being the most common. Of note, grade 3 or higher hemorrhage and atrial fibrillation, which can be seen with BTK inhibitors, were rare, occurring in 3.7% and 1.2% of patients, respectively. Based on the results of this study, pirtobrutinib has been approved by the FDA for patients with relapsed/refractory MCL after at least two prior lines of therapy, including a BTK inhibitor. This is an appealing oral option for patients with relapsed disease.

Options for patients with relapsed/refractory large B-cell lymphoma (LBCL) have also significantly increased in recent years. One of the most important advances in this disease has been the use of anti-CD19 CAR T-cell therapy. There are currently three FDA-approved options for patients with relapsed/refractory LBCL who have received at least two prior lines of therapy.^1-3 More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for the second line based on the results of the ZUMA-7 and TRANSFORM studies, respectively.^4,5

Longer follow-up of the ZUMA-7 trial continues to confirm the advantage of axi-cel over standard-care therapy for patients with primary refractory or early relapse of disease, now with evidence of an overall survival advantage (Westin et al). The ZUMA-7 trial included 359 adults with LBCL (refractory to or relapsed within 12 months of first-line treatment) who were randomly assigned to receive axi-cel (n = 180) or standard care (n = 179). At a median follow-up of 47.2 mo, patients receiving axi-cel vs standard care had a significantly longer median overall survival (not reached vs 31.1 mo; hazard ratio [HR] 0.73; P = .03) and an absolute improvement in overall survival (8.6 percentage points at 4 years). No new treatment-related deaths were reported since the primary event-free survival analysis. These data confirm that early use of axi-cel is preferred over standard-care therapy with high-dose chemotherapy and autologous stem cell transplantation.

Another important study that was recently published looked at the role of mental health on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (Kuczmarski et al). Though it is known that mental health disorders can decrease the quality of life of patients with cancer, there is limited information on the survival implications of these issues. A recent retrospective cohort study analyzed the data of 13,244 patients aged 67 years or older with DLBCL from the Surveillance, Epidemiology, and End Results (SEER)–Medicare registry, of which, 2094 patients had depression, anxiety, or both at the time of their DLBCL diagnosis. At a median follow-up of 2.0 years, patients with depression, anxiety, or both vs without any mental disorder had significantly lower 5-year overall survival rates (27.0% vs 37.4%; HR 1.37; 95% CI 1.29-1.44). They also found that those patients with preexisting depression vs without any mental disorder have the worst survival (23.4% vs 38.0%; HR 1.37; P < .0001). Though the mechanism accounting for decreased survival is not clear, the authors postulate that mental health disorders may lead to delays or interruptions in lymphoma-directed therapy. They also note the potential for increased barriers to care in patients with mental health disorders, which may result in nonadherence in this patient population. Regardless, these results highlight the importance of mental health screening and interventions in patients with DLBCL.

Additional References

1. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. doi: 10.1056/NEJMoa1707447
    
2. Schuster SJ, Bishop MR, Tam CS, et al; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. doi: 10.1056/NEJMoa1804980
    
3. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. doi: 10.1016/S0140-6736(20)31366-0
    
4. Locke FL, Miklos DB, Jacobson CA, et al; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133
5. Kamdar M, Solomon SR, Arnason J, et al; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6

Mantle cell lymphoma (MCL) is a rare and often heterogenous subtype of non-Hodgkin lymphoma (NHL). Though patients can experience prolonged remissions after frontline therapy, most patients ultimately relapse. Treatment of relapsed/refractory disease can be challenging, but there have recently been a growing number of therapeutic options in this setting. Covalent Bruton tyrosine kinase (BTK) inhibitors, for example, have demonstrated activity in patients with MCL and are approved by the US Food and Drug Administration (FDA) for relapsed/refractory disease. Chimeric antigen receptor (CAR) T-cell therapy is also an effective option for relapsed/refractory disease, though this is typically available only at select centers and is associated with toxicities, such as cytokine release syndrome and neurologic toxicity.

Recently, a novel BTK inhibitor, pirtobrutinib, has also been studied across NHL, including MCL (Wang et al) Pirtobrutinib is a selective, noncovalent BTK inhibitor with the ability to bind both the C481S-mutant and wild-type BTK. The multicenter, phase 1/2 BRUIN study included 90 patients with MCL who were previously treated with a covalent BTK inhibitor. Patients in the phase 1 portion of the study were treated with oral pirtobrutinib at a dose of 25-300 mg once daily, and patients in the phase 2 study were treated at the recommended dose of 200 mg once daily. The overall response rate was 57.8% (95% CI 46.9%-68.1%), with the complete response rate being 20.0%. At a median follow-up of 12 months, the median duration of response was 21.6 (95% CI 7.5 to not reached) months. Treatment-related adverse events that were grade 3 or higher were not frequent, with neutropenia (8.5%) being the most common. Of note, grade 3 or higher hemorrhage and atrial fibrillation, which can be seen with BTK inhibitors, were rare, occurring in 3.7% and 1.2% of patients, respectively. Based on the results of this study, pirtobrutinib has been approved by the FDA for patients with relapsed/refractory MCL after at least two prior lines of therapy, including a BTK inhibitor. This is an appealing oral option for patients with relapsed disease.

Options for patients with relapsed/refractory large B-cell lymphoma (LBCL) have also significantly increased in recent years. One of the most important advances in this disease has been the use of anti-CD19 CAR T-cell therapy. There are currently three FDA-approved options for patients with relapsed/refractory LBCL who have received at least two prior lines of therapy.^1-3 More recently, axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have also been approved for the second line based on the results of the ZUMA-7 and TRANSFORM studies, respectively.^4,5

Longer follow-up of the ZUMA-7 trial continues to confirm the advantage of axi-cel over standard-care therapy for patients with primary refractory or early relapse of disease, now with evidence of an overall survival advantage (Westin et al). The ZUMA-7 trial included 359 adults with LBCL (refractory to or relapsed within 12 months of first-line treatment) who were randomly assigned to receive axi-cel (n = 180) or standard care (n = 179). At a median follow-up of 47.2 mo, patients receiving axi-cel vs standard care had a significantly longer median overall survival (not reached vs 31.1 mo; hazard ratio [HR] 0.73; P = .03) and an absolute improvement in overall survival (8.6 percentage points at 4 years). No new treatment-related deaths were reported since the primary event-free survival analysis. These data confirm that early use of axi-cel is preferred over standard-care therapy with high-dose chemotherapy and autologous stem cell transplantation.

Another important study that was recently published looked at the role of mental health on outcomes in patients with diffuse large B-cell lymphoma (DLBCL) (Kuczmarski et al). Though it is known that mental health disorders can decrease the quality of life of patients with cancer, there is limited information on the survival implications of these issues. A recent retrospective cohort study analyzed the data of 13,244 patients aged 67 years or older with DLBCL from the Surveillance, Epidemiology, and End Results (SEER)–Medicare registry, of which, 2094 patients had depression, anxiety, or both at the time of their DLBCL diagnosis. At a median follow-up of 2.0 years, patients with depression, anxiety, or both vs without any mental disorder had significantly lower 5-year overall survival rates (27.0% vs 37.4%; HR 1.37; 95% CI 1.29-1.44). They also found that those patients with preexisting depression vs without any mental disorder have the worst survival (23.4% vs 38.0%; HR 1.37; P < .0001). Though the mechanism accounting for decreased survival is not clear, the authors postulate that mental health disorders may lead to delays or interruptions in lymphoma-directed therapy. They also note the potential for increased barriers to care in patients with mental health disorders, which may result in nonadherence in this patient population. Regardless, these results highlight the importance of mental health screening and interventions in patients with DLBCL.

Additional References

1. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-Cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017;377:2531-2544. doi: 10.1056/NEJMoa1707447
    
2. Schuster SJ, Bishop MR, Tam CS, et al; JULIET Investigators. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45-56. doi: 10.1056/NEJMoa1804980
    
3. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): A multicentre seamless design study. Lancet. 2020;396:839-852. doi: 10.1016/S0140-6736(20)31366-0
    
4. Locke FL, Miklos DB, Jacobson CA, et al; All ZUMA-7 Investigators and Contributing Kite Members. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386:640-654. doi: 10.1056/NEJMoa2116133
5. Kamdar M, Solomon SR, Arnason J, et al; TRANSFORM Investigators. Lisocabtagene maraleucel versus standard of care with salvage chemotherapy followed by autologous stem cell transplantation as second-line treatment in patients with relapsed or refractory large B-cell lymphoma (TRANSFORM): Results from an interim analysis of an open-label, randomised, phase 3 trial. Lancet. 2022;399:2294-2308. doi: 10.1016/S0140-6736(22)00662-6

Key clinical point: In transplant-ineligible patients with untreated mantle cell lymphoma (MCL), bendamustine, rituximab, ibrutinib, and rituximab maintenance (BR-Ibrutinib+R) and bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) should be the preferred immunotherapy regimens for improving progression-free survival (PFS) and overall survival (OS), respectively.

Major finding: BR-Ibrutinib+R resulted in the best PFS, with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69% followed by bendamustine, rituximab, and rituximab maintenance (SUCRA 0.76; PbBT 11%). VR-CAP provided the best OS, with a SUCRA of 0.89 and PbBT of 63% followed by bendamustine and rituximab regimen (SUCRA 0.74; PbBT 22%).

Study details: The data come from a network meta-analysis of nine randomized controlled trials involving 2897 transplant-ineligible patients who received first-line chemoimmunotherapy for MCL.

Disclosures: This study was funded by the Achievement Transformation Project and others. The authors declared no conflicts of interest.

Source: Jing C et al. Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials. Cancer Med. 2023 (Jun 1). doi: 10.1002/cam4.6183

Key clinical point: In transplant-ineligible patients with untreated mantle cell lymphoma (MCL), bendamustine, rituximab, ibrutinib, and rituximab maintenance (BR-Ibrutinib+R) and bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) should be the preferred immunotherapy regimens for improving progression-free survival (PFS) and overall survival (OS), respectively.

Major finding: BR-Ibrutinib+R resulted in the best PFS, with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69% followed by bendamustine, rituximab, and rituximab maintenance (SUCRA 0.76; PbBT 11%). VR-CAP provided the best OS, with a SUCRA of 0.89 and PbBT of 63% followed by bendamustine and rituximab regimen (SUCRA 0.74; PbBT 22%).

Study details: The data come from a network meta-analysis of nine randomized controlled trials involving 2897 transplant-ineligible patients who received first-line chemoimmunotherapy for MCL.

Disclosures: This study was funded by the Achievement Transformation Project and others. The authors declared no conflicts of interest.

Source: Jing C et al. Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials. Cancer Med. 2023 (Jun 1). doi: 10.1002/cam4.6183

Key clinical point: In transplant-ineligible patients with untreated mantle cell lymphoma (MCL), bendamustine, rituximab, ibrutinib, and rituximab maintenance (BR-Ibrutinib+R) and bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) should be the preferred immunotherapy regimens for improving progression-free survival (PFS) and overall survival (OS), respectively.

Major finding: BR-Ibrutinib+R resulted in the best PFS, with a surface under the cumulative ranking curve (SUCRA) of 0.89 and probability of being the best treatment (PbBT) of 69% followed by bendamustine, rituximab, and rituximab maintenance (SUCRA 0.76; PbBT 11%). VR-CAP provided the best OS, with a SUCRA of 0.89 and PbBT of 63% followed by bendamustine and rituximab regimen (SUCRA 0.74; PbBT 22%).

Study details: The data come from a network meta-analysis of nine randomized controlled trials involving 2897 transplant-ineligible patients who received first-line chemoimmunotherapy for MCL.

Disclosures: This study was funded by the Achievement Transformation Project and others. The authors declared no conflicts of interest.

Source: Jing C et al. Efficacy of front-line immunochemotherapy for transplant-ineligible mantle cell lymphoma: A network meta-analysis of randomized controlled trials. Cancer Med. 2023 (Jun 1). doi: 10.1002/cam4.6183

Key clinical point: The combination of obinutuzumab and bendamustine is a potent treatment option with a manageable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 33.4 months, the median progression-free survival was 26.0 (95% CI 20.3-31.7) months and the median overall survival was not reached. The overall response rate was 78.6%, with 28.6% of patients achieving complete response. The grade ≥3 adverse event (AE) rate was 76.4%, with neutropenia (58.3%), thrombocytopenia (26.4%), and febrile neutropenia (11.1%) being the most common grade ≥3 AE.

Study details: Findings are from the multicenter, phase 2 GABRIELL study that included 72 adult patients with relapsed or refractory CLL who received ≤6 cycles of obinutuzumab plus bendamustine.

Disclosures: This study was funded by Roche Farma SA. Some authors declared serving as advisory board or speaker bureau members with or without honoraria and receiving research support or attendance fees and travel expenses from Roche or others.

Source: Bravo J et al on behalf of the GABRIELL Study Group/Investigators. Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: The phase II GABRIELL study. Leuk Lymphoma. 2023;64(5):913-926 (May 31). doi: 10.1080/10428194.2023.2216327

Key clinical point: The combination of obinutuzumab and bendamustine is a potent treatment option with a manageable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 33.4 months, the median progression-free survival was 26.0 (95% CI 20.3-31.7) months and the median overall survival was not reached. The overall response rate was 78.6%, with 28.6% of patients achieving complete response. The grade ≥3 adverse event (AE) rate was 76.4%, with neutropenia (58.3%), thrombocytopenia (26.4%), and febrile neutropenia (11.1%) being the most common grade ≥3 AE.

Study details: Findings are from the multicenter, phase 2 GABRIELL study that included 72 adult patients with relapsed or refractory CLL who received ≤6 cycles of obinutuzumab plus bendamustine.

Disclosures: This study was funded by Roche Farma SA. Some authors declared serving as advisory board or speaker bureau members with or without honoraria and receiving research support or attendance fees and travel expenses from Roche or others.

Source: Bravo J et al on behalf of the GABRIELL Study Group/Investigators. Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: The phase II GABRIELL study. Leuk Lymphoma. 2023;64(5):913-926 (May 31). doi: 10.1080/10428194.2023.2216327

Key clinical point: The combination of obinutuzumab and bendamustine is a potent treatment option with a manageable safety profile for patients with relapsed or refractory chronic lymphocytic leukemia (CLL).

Major finding: At a median follow-up of 33.4 months, the median progression-free survival was 26.0 (95% CI 20.3-31.7) months and the median overall survival was not reached. The overall response rate was 78.6%, with 28.6% of patients achieving complete response. The grade ≥3 adverse event (AE) rate was 76.4%, with neutropenia (58.3%), thrombocytopenia (26.4%), and febrile neutropenia (11.1%) being the most common grade ≥3 AE.

Study details: Findings are from the multicenter, phase 2 GABRIELL study that included 72 adult patients with relapsed or refractory CLL who received ≤6 cycles of obinutuzumab plus bendamustine.

Disclosures: This study was funded by Roche Farma SA. Some authors declared serving as advisory board or speaker bureau members with or without honoraria and receiving research support or attendance fees and travel expenses from Roche or others.

Source: Bravo J et al on behalf of the GABRIELL Study Group/Investigators. Obinutuzumab plus bendamustine for relapsed/refractory chronic lymphocytic leukemia and predictive and prognostic impact of genetic alterations: The phase II GABRIELL study. Leuk Lymphoma. 2023;64(5):913-926 (May 31). doi: 10.1080/10428194.2023.2216327

Key clinical point: Compared with chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitor (BTKi) therapy combined with anti-CD20 antibody therapy improves clinical outcomes in patients with treatment-naive chronic lymphocytic leukemia (CLL) without causing increased toxicity.

Major finding: Patients receiving BTKi+anti-CD20 antibody vs CIT had significantly prolonged progression-free survival (hazard ratio 0.25; 95% CI 0.15-0.42) and higher objective response rates (risk ratio [RR] 1.16; 95% CI 1.13-1.20) and a comparable risk for grade ≥3 adverse events (RR 1.04; 95% CI 0.92-1.17).

Study details: The data come from a meta-analysis of four randomized controlled trials involving 1479 patients with treatment-naive CLL who had been randomized to receive CIT or BTKi+anti-CD20 antibody therapy.

Disclosures: This study was partly supported by the Ministry of Science and Technology, Taiwan, and Taipei Medical University, Taiwan. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of Bruton tyrosine kinase inhibitor plus anti-CD20 antibody therapy compared with chemoimmunotherapy as front-line treatment for chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized controlled trials. J Immunother. 2023 (May 23). doi: 10.1097/CJI.0000000000000471

Key clinical point: Compared with chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitor (BTKi) therapy combined with anti-CD20 antibody therapy improves clinical outcomes in patients with treatment-naive chronic lymphocytic leukemia (CLL) without causing increased toxicity.

Major finding: Patients receiving BTKi+anti-CD20 antibody vs CIT had significantly prolonged progression-free survival (hazard ratio 0.25; 95% CI 0.15-0.42) and higher objective response rates (risk ratio [RR] 1.16; 95% CI 1.13-1.20) and a comparable risk for grade ≥3 adverse events (RR 1.04; 95% CI 0.92-1.17).

Study details: The data come from a meta-analysis of four randomized controlled trials involving 1479 patients with treatment-naive CLL who had been randomized to receive CIT or BTKi+anti-CD20 antibody therapy.

Disclosures: This study was partly supported by the Ministry of Science and Technology, Taiwan, and Taipei Medical University, Taiwan. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of Bruton tyrosine kinase inhibitor plus anti-CD20 antibody therapy compared with chemoimmunotherapy as front-line treatment for chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized controlled trials. J Immunother. 2023 (May 23). doi: 10.1097/CJI.0000000000000471

Key clinical point: Compared with chemoimmunotherapy (CIT), Bruton tyrosine kinase inhibitor (BTKi) therapy combined with anti-CD20 antibody therapy improves clinical outcomes in patients with treatment-naive chronic lymphocytic leukemia (CLL) without causing increased toxicity.

Major finding: Patients receiving BTKi+anti-CD20 antibody vs CIT had significantly prolonged progression-free survival (hazard ratio 0.25; 95% CI 0.15-0.42) and higher objective response rates (risk ratio [RR] 1.16; 95% CI 1.13-1.20) and a comparable risk for grade ≥3 adverse events (RR 1.04; 95% CI 0.92-1.17).

Study details: The data come from a meta-analysis of four randomized controlled trials involving 1479 patients with treatment-naive CLL who had been randomized to receive CIT or BTKi+anti-CD20 antibody therapy.

Disclosures: This study was partly supported by the Ministry of Science and Technology, Taiwan, and Taipei Medical University, Taiwan. The authors declared no conflicts of interest.

Source: Nguyen TT et al. Efficacy and safety of Bruton tyrosine kinase inhibitor plus anti-CD20 antibody therapy compared with chemoimmunotherapy as front-line treatment for chronic lymphocytic leukemia: A systematic review and meta-analysis of randomized controlled trials. J Immunother. 2023 (May 23). doi: 10.1097/CJI.0000000000000471

Key clinical point: High-dose rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-High-CHOP)/cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) followed by high-dose chemotherapy (HDC) with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED), and autologous peripheral blood stem cell transplantation (auto-PBSCT) provided favorable long-term survival outcomes in younger patients with untreated advanced mantle cell lymphoma (MCL).

Major finding: At 6-year median follow-up, the 5- and 8-year progression-free survival rates were 52.3% (95% CI 36.7%-65.7%) and 17.1% (95% CI 5.2%-34.7%), respectively, and the overall survival rates were 75.0% (95% CI 59.4%-85.3%) and 69.0% (95% CI 52.3%-80.9%), respectively. The incidence of secondary malignancies (11.1%) and continuous relapses was high.

Study details: This final analysis of the JCOG0406 study included 45 patients age ≤ 65 years with untreated advanced MCL who received R-High-CHOP/CHASER followed by HDC with LEED and auto-PBSCT.

Disclosures: This study was supported by Health and Labour Sciences Research Grants (Japan) and others. S Nakamura declared being an Editorial Board Member of Cancer Science. Some authors reported ties with various organizations.

Source: Ogura M et al. Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406. Cancer Sci. 2023 (May 26). doi: 10.1111/cas.15849

Key clinical point: High-dose rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-High-CHOP)/cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) followed by high-dose chemotherapy (HDC) with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED), and autologous peripheral blood stem cell transplantation (auto-PBSCT) provided favorable long-term survival outcomes in younger patients with untreated advanced mantle cell lymphoma (MCL).

Major finding: At 6-year median follow-up, the 5- and 8-year progression-free survival rates were 52.3% (95% CI 36.7%-65.7%) and 17.1% (95% CI 5.2%-34.7%), respectively, and the overall survival rates were 75.0% (95% CI 59.4%-85.3%) and 69.0% (95% CI 52.3%-80.9%), respectively. The incidence of secondary malignancies (11.1%) and continuous relapses was high.

Study details: This final analysis of the JCOG0406 study included 45 patients age ≤ 65 years with untreated advanced MCL who received R-High-CHOP/CHASER followed by HDC with LEED and auto-PBSCT.

Disclosures: This study was supported by Health and Labour Sciences Research Grants (Japan) and others. S Nakamura declared being an Editorial Board Member of Cancer Science. Some authors reported ties with various organizations.

Source: Ogura M et al. Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406. Cancer Sci. 2023 (May 26). doi: 10.1111/cas.15849

Key clinical point: High-dose rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-High-CHOP)/cyclophosphamide, high-dose cytarabine, dexamethasone, etoposide, and rituximab (CHASER) followed by high-dose chemotherapy (HDC) with melphalan, cyclophosphamide, etoposide, and dexamethasone (LEED), and autologous peripheral blood stem cell transplantation (auto-PBSCT) provided favorable long-term survival outcomes in younger patients with untreated advanced mantle cell lymphoma (MCL).

Major finding: At 6-year median follow-up, the 5- and 8-year progression-free survival rates were 52.3% (95% CI 36.7%-65.7%) and 17.1% (95% CI 5.2%-34.7%), respectively, and the overall survival rates were 75.0% (95% CI 59.4%-85.3%) and 69.0% (95% CI 52.3%-80.9%), respectively. The incidence of secondary malignancies (11.1%) and continuous relapses was high.

Study details: This final analysis of the JCOG0406 study included 45 patients age ≤ 65 years with untreated advanced MCL who received R-High-CHOP/CHASER followed by HDC with LEED and auto-PBSCT.

Disclosures: This study was supported by Health and Labour Sciences Research Grants (Japan) and others. S Nakamura declared being an Editorial Board Member of Cancer Science. Some authors reported ties with various organizations.

Source: Ogura M et al. Long-term follow-up after R-High CHOP/CHASER/LEED with Auto-PBSCT in untreated mantle cell lymphoma-Final analysis of JCOG0406. Cancer Sci. 2023 (May 26). doi: 10.1111/cas.15849

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: Compared with polatuzumab vedotin+bendamustine+rituximab (pola-BR) and rituximab+lenalidomide (R2), tafasitamab+lenalidomide provided a significant survival benefit in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Major finding: A significant overall survival (OS) benefit was observed with tafasitamab+lenalidomide vs pola-BR (hazard ratio [HR] 0.441; P = .034) and R2 (HR 0.435; P = .012). However, the OS was similar between the tafasitamab+lenalidomide and CD19-chimeric antigen receptor T-cell groups (CAR-T; HR 0.953; P = .892).

Study details: This expanded analysis of the RE-MIND2 study of propensity score-matched transplant-ineligible patients with R/R DLBCL treated with ≥2 systemic therapies who received tafasitamab+lenalidomide in the L-MIND trial and those who received pola-BR (24 pairs), R2 (33 pairs), or CAR-T (37 pairs) from an observational cohort.

Disclosures: This study was sponsored by MorphoSys AG. Some authors declared serving as consultants, advisory board members, or speakers and receiving research funding, honoraria, or travel support from MorphoSys and others. Four authors declared being employees of or holding equities in MorphoSys.

Source: Nowakowski GS et al. RE-MIND2: Comparative effectiveness of tafasitamab plus lenalidomide versus polatuzumab vedotin/bendamustine/rituximab (pola‑BR), CAR‑T therapies, and lenalidomide/rituximab (R2) based on real‑world data in patients with relapsed/refractory diffuse large B‑cell lymphoma. Ann Hematol. 2023;102:1773-1787 (May 12). doi: 10.1007/s00277-023-05196-4

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744

Key clinical point: The rituximab, bendamustine, and low-dose cytarabine (R-BAC) regimen, not succeeded by maintenance therapy, induces long-term responses in previously untreated elderly patients with mantle cell lymphoma (MCL).

Major finding: After a median follow-up of 86 months, the median overall survival (OS) and progression-free survival (PFS) were not reached; the 7-year PFS and OS rates were 55% (95% CI 41%-67%) and 63% (95% CI 49%-74%), respectively. The 7-year duration of response rate among the 52 responding patients was 59% (95% CI 44%-71%). No signal of late toxicity was reported.

Study details: Findings are from a long-term analysis of the FIL-RBAC500 trial that included 57 previously untreated elderly patients with MCL who received the R-BAC regimen.

Disclosures: This study was supported by Progetto di Ricerca Sanitaria Finalizzata (Italy) grants and other sources. Some authors declared serving as advisory board members or consultants and receiving research funding, speaker honoraria, or travel expenses and accommodations from various sources.

Source: Tisi MC et al. Long term follow-up of rituximab plus bendamustine and cytarabine (R-BAC) in elderly patients with newly diagnosed MCL. Blood Adv. 2023 (May 12). doi: 10.1182/bloodadvances.2023009744