B Cell Lymphoma

Key clinical point: High serum levels of the M2 macrophage marker soluble CD163 could be used as an independent negative prognostic marker in patients with newly diagnosed or relapsed mantle cell lymphoma (MCL).

Major finding: Above-median levels of soluble CD163 (>3000 ng/mL) were significantly associated with shorter progression-free survival (adjusted hazard ratio [aHR] 3.48; P =.006) and overall survival (aHR 4.33; P =.016).

Study details: This study analyzed serum samples from 131 patients with newly diagnosed or relapsed MCL who received immunochemotherapy or targeted treatments (mainly rituximab, ibrutinib, and lenalidomide), respectively.

Disclosures: This study was supported by grants from the Swedish Cancer Society and others. Some authors declared serving as advisory board members or scientific advisors or receiving research funding or honoraria from various organizations.

Source: Nikkarinen A et al. Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma. Blood Adv. 2023 (Jun 30). Doi: 10.1182/bloodadvances.2023010052

Key clinical point: High serum levels of the M2 macrophage marker soluble CD163 could be used as an independent negative prognostic marker in patients with newly diagnosed or relapsed mantle cell lymphoma (MCL).

Major finding: Above-median levels of soluble CD163 (>3000 ng/mL) were significantly associated with shorter progression-free survival (adjusted hazard ratio [aHR] 3.48; P =.006) and overall survival (aHR 4.33; P =.016).

Study details: This study analyzed serum samples from 131 patients with newly diagnosed or relapsed MCL who received immunochemotherapy or targeted treatments (mainly rituximab, ibrutinib, and lenalidomide), respectively.

Disclosures: This study was supported by grants from the Swedish Cancer Society and others. Some authors declared serving as advisory board members or scientific advisors or receiving research funding or honoraria from various organizations.

Source: Nikkarinen A et al. Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma. Blood Adv. 2023 (Jun 30). Doi: 10.1182/bloodadvances.2023010052

Key clinical point: High serum levels of the M2 macrophage marker soluble CD163 could be used as an independent negative prognostic marker in patients with newly diagnosed or relapsed mantle cell lymphoma (MCL).

Major finding: Above-median levels of soluble CD163 (>3000 ng/mL) were significantly associated with shorter progression-free survival (adjusted hazard ratio [aHR] 3.48; P =.006) and overall survival (aHR 4.33; P =.016).

Study details: This study analyzed serum samples from 131 patients with newly diagnosed or relapsed MCL who received immunochemotherapy or targeted treatments (mainly rituximab, ibrutinib, and lenalidomide), respectively.

Disclosures: This study was supported by grants from the Swedish Cancer Society and others. Some authors declared serving as advisory board members or scientific advisors or receiving research funding or honoraria from various organizations.

Source: Nikkarinen A et al. Soluble CD163 predicts outcome in both chemoimmunotherapy and targeted therapy-treated mantle cell lymphoma. Blood Adv. 2023 (Jun 30). Doi: 10.1182/bloodadvances.2023010052

Key clinical point: Ibrutinib showed efficacy in a real-world cohort of patients with previously untreated high-risk chronic lymphocytic leukemia (CLL) carrying 17p- or TP53 mutations (TP53 aberrations).

Major finding: At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death were the reasons for discontinuation in 45.8% of patients.

Study details: This real-world registry study analyzed the data of 747 patients with CLL and TP53 aberrations treated with first-line ibrutinib.

Disclosures: This study was funded by the University of Ferrara, Italy, and others. Some authors, including the lead author, declared receiving research support, travel grants, or honoraria for speakers’ bureau or advisory board participation from various sources.

Source: Rigolin GM et al. Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: A nationwide registry study from the Italian Medicines Agency. Blood Cancer J. 2023;13:99 (Jun 28). Doi: 10.1038/s41408-023-00865-z

Key clinical point: Ibrutinib showed efficacy in a real-world cohort of patients with previously untreated high-risk chronic lymphocytic leukemia (CLL) carrying 17p- or TP53 mutations (TP53 aberrations).

Major finding: At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death were the reasons for discontinuation in 45.8% of patients.

Study details: This real-world registry study analyzed the data of 747 patients with CLL and TP53 aberrations treated with first-line ibrutinib.

Disclosures: This study was funded by the University of Ferrara, Italy, and others. Some authors, including the lead author, declared receiving research support, travel grants, or honoraria for speakers’ bureau or advisory board participation from various sources.

Source: Rigolin GM et al. Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: A nationwide registry study from the Italian Medicines Agency. Blood Cancer J. 2023;13:99 (Jun 28). Doi: 10.1038/s41408-023-00865-z

Key clinical point: Ibrutinib showed efficacy in a real-world cohort of patients with previously untreated high-risk chronic lymphocytic leukemia (CLL) carrying 17p- or TP53 mutations (TP53 aberrations).

Major finding: At 24 months, the median overall survival was not reached; the estimated treatment persistence and survival rates were 63.4% (95% CI 60.0%-67.0%) and 82.6% (95% CI 79.9%-85.4%), respectively. The median time to treatment discontinuation was 37.4 months (95% CI 34.8-42.2 months). Disease progression or death were the reasons for discontinuation in 45.8% of patients.

Study details: This real-world registry study analyzed the data of 747 patients with CLL and TP53 aberrations treated with first-line ibrutinib.

Disclosures: This study was funded by the University of Ferrara, Italy, and others. Some authors, including the lead author, declared receiving research support, travel grants, or honoraria for speakers’ bureau or advisory board participation from various sources.

Source: Rigolin GM et al. Outcomes in patients with chronic lymphocytic leukemia and TP53 aberration who received first-line ibrutinib: A nationwide registry study from the Italian Medicines Agency. Blood Cancer J. 2023;13:99 (Jun 28). Doi: 10.1038/s41408-023-00865-z

Key clinical point: Front-line chemo-free combination therapy with rituximab and lenalidomide was moderately active in elderly frail patients with diffuse large B-cell lymphoma (DLBCL) who were ineligible for conventional cytotoxic therapy.

Major finding: The overall response rate was 50.8% (95% CI 38.1%-63.4%), with 27.7% of patients achieving a complete response. After a 24-month median follow-up, the median progression-free survival was 14.0 months (95% CI 6.8-not reached) and the 2-year duration of response rate was 64.6% (95% CI 42.1%-80.1%). The grade ≥3 extra-hematological toxicity event rate was 52.3%.

Study details: Findings are from the prospective phase 2 FIL_ReRi trial including 65 frail patients aged ≥70 years with untreated DLBCL who received ≤6 cycles of lenalidomide+rituximab; patients with partial or complete response at cycle 6 received lenalidomide for 12 cycles or until progression or unacceptable toxicity.

Disclosures: This study was sponsored by Fondazione Italiana Linfomi (FIL), Alessandria, Italy. Some authors declared participating on data safety monitoring or advisory boards of, serving in leadership roles in, or receiving consulting fees or speaker honoraria from various sources, including FIL.

Source: Gini G et al. Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: The FIL_ReRi phase 2 study. Blood. 2023 (Jul 7). Doi: 10.1182/blood.2022019173

Key clinical point: Front-line chemo-free combination therapy with rituximab and lenalidomide was moderately active in elderly frail patients with diffuse large B-cell lymphoma (DLBCL) who were ineligible for conventional cytotoxic therapy.

Major finding: The overall response rate was 50.8% (95% CI 38.1%-63.4%), with 27.7% of patients achieving a complete response. After a 24-month median follow-up, the median progression-free survival was 14.0 months (95% CI 6.8-not reached) and the 2-year duration of response rate was 64.6% (95% CI 42.1%-80.1%). The grade ≥3 extra-hematological toxicity event rate was 52.3%.

Study details: Findings are from the prospective phase 2 FIL_ReRi trial including 65 frail patients aged ≥70 years with untreated DLBCL who received ≤6 cycles of lenalidomide+rituximab; patients with partial or complete response at cycle 6 received lenalidomide for 12 cycles or until progression or unacceptable toxicity.

Disclosures: This study was sponsored by Fondazione Italiana Linfomi (FIL), Alessandria, Italy. Some authors declared participating on data safety monitoring or advisory boards of, serving in leadership roles in, or receiving consulting fees or speaker honoraria from various sources, including FIL.

Source: Gini G et al. Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: The FIL_ReRi phase 2 study. Blood. 2023 (Jul 7). Doi: 10.1182/blood.2022019173

Key clinical point: Front-line chemo-free combination therapy with rituximab and lenalidomide was moderately active in elderly frail patients with diffuse large B-cell lymphoma (DLBCL) who were ineligible for conventional cytotoxic therapy.

Major finding: The overall response rate was 50.8% (95% CI 38.1%-63.4%), with 27.7% of patients achieving a complete response. After a 24-month median follow-up, the median progression-free survival was 14.0 months (95% CI 6.8-not reached) and the 2-year duration of response rate was 64.6% (95% CI 42.1%-80.1%). The grade ≥3 extra-hematological toxicity event rate was 52.3%.

Study details: Findings are from the prospective phase 2 FIL_ReRi trial including 65 frail patients aged ≥70 years with untreated DLBCL who received ≤6 cycles of lenalidomide+rituximab; patients with partial or complete response at cycle 6 received lenalidomide for 12 cycles or until progression or unacceptable toxicity.

Disclosures: This study was sponsored by Fondazione Italiana Linfomi (FIL), Alessandria, Italy. Some authors declared participating on data safety monitoring or advisory boards of, serving in leadership roles in, or receiving consulting fees or speaker honoraria from various sources, including FIL.

Source: Gini G et al. Lenalidomide plus rituximab for the initial treatment of elderly frail patients with DLBCL: The FIL_ReRi phase 2 study. Blood. 2023 (Jul 7). Doi: 10.1182/blood.2022019173

Key clinical point: Nivolumab+brentuximab vedotin (BV) showed long-term efficacy and safety in patients with treatment-resistant relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBL).

Major finding: After a median follow-up of 39.6 months, the objective response rate was 73.3% (95% CI 54.1%-87.7%), with 40.0% and 33.3% of patients achieving complete and partial responses, respectively. The median duration of response or overall survival was not reached, and the median progression-free survival was 26.0 (95% CI 2.6-not reached) months. No new safety signals were reported.

Study details: This 3-year follow-up study of phase 1/2 CheckMate 436 trial included 30 patients age ≥15 years with R/R PMBL previously treated with high-dose chemotherapy+autologous hematopoietic cell transplantation or ≥2 prior multiagent chemotherapies who received 240 mg nivolumab and 1.8 mg/kg BV once every 3 weeks.

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Seagen. Some authors declared serving as advisory board members and receiving consulting fees, honoraria, or research grants from BMS, Seagen, and others. Three authors declared being employees of or holding stocks in BMS or Seagen.

Source: Zinzani PL et al. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: A 3-year follow-up. Blood Adv. 2023 (Jun 23). Doi: 10.1182/bloodadvances.2023010254

Key clinical point: Nivolumab+brentuximab vedotin (BV) showed long-term efficacy and safety in patients with treatment-resistant relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBL).

Major finding: After a median follow-up of 39.6 months, the objective response rate was 73.3% (95% CI 54.1%-87.7%), with 40.0% and 33.3% of patients achieving complete and partial responses, respectively. The median duration of response or overall survival was not reached, and the median progression-free survival was 26.0 (95% CI 2.6-not reached) months. No new safety signals were reported.

Study details: This 3-year follow-up study of phase 1/2 CheckMate 436 trial included 30 patients age ≥15 years with R/R PMBL previously treated with high-dose chemotherapy+autologous hematopoietic cell transplantation or ≥2 prior multiagent chemotherapies who received 240 mg nivolumab and 1.8 mg/kg BV once every 3 weeks.

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Seagen. Some authors declared serving as advisory board members and receiving consulting fees, honoraria, or research grants from BMS, Seagen, and others. Three authors declared being employees of or holding stocks in BMS or Seagen.

Source: Zinzani PL et al. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: A 3-year follow-up. Blood Adv. 2023 (Jun 23). Doi: 10.1182/bloodadvances.2023010254

Key clinical point: Nivolumab+brentuximab vedotin (BV) showed long-term efficacy and safety in patients with treatment-resistant relapsed or refractory (R/R) primary mediastinal large B-cell lymphoma (PMBL).

Major finding: After a median follow-up of 39.6 months, the objective response rate was 73.3% (95% CI 54.1%-87.7%), with 40.0% and 33.3% of patients achieving complete and partial responses, respectively. The median duration of response or overall survival was not reached, and the median progression-free survival was 26.0 (95% CI 2.6-not reached) months. No new safety signals were reported.

Study details: This 3-year follow-up study of phase 1/2 CheckMate 436 trial included 30 patients age ≥15 years with R/R PMBL previously treated with high-dose chemotherapy+autologous hematopoietic cell transplantation or ≥2 prior multiagent chemotherapies who received 240 mg nivolumab and 1.8 mg/kg BV once every 3 weeks.

Disclosures: This study was supported by Bristol Myers Squibb (BMS) and Seagen. Some authors declared serving as advisory board members and receiving consulting fees, honoraria, or research grants from BMS, Seagen, and others. Three authors declared being employees of or holding stocks in BMS or Seagen.

Source: Zinzani PL et al. Nivolumab combined with brentuximab vedotin for R/R primary mediastinal large B-cell lymphoma: A 3-year follow-up. Blood Adv. 2023 (Jun 23). Doi: 10.1182/bloodadvances.2023010254

Key clinical point: BCL6 positivity is associated with worse survival outcomes and a higher Ki67 index and shows a positive correlation with CD10 positivity in patients with mantle cell lymphoma (MCL).

Major finding: A positive vs negative expression of BCL6 was associated with a significantly shorter median overall survival (14 vs 43 months; P =.01) and was significantly correlated with CD10 positivity (odds ratio 5.11; P =.0000286) and a higher Ki67 index (P =.0094).

Study details: The data come from a systematic review and meta-analysis of 10 studies that involved 102 patients with MCL and reported BCL6- and CD10-positive or -negative MCL and Ki67% in BCL6-positive or -negative MCL.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Source: Castillo DR et al. Unveiling the prognostic significance of BCL6+/CD10+ mantle cell lymphoma: Meta-analysis of individual patients and systematic review. Int J Mol Sci. 2023;24(12):10207 (Jun 16). Doi: 10.3390/ijms241210207

Key clinical point: BCL6 positivity is associated with worse survival outcomes and a higher Ki67 index and shows a positive correlation with CD10 positivity in patients with mantle cell lymphoma (MCL).

Major finding: A positive vs negative expression of BCL6 was associated with a significantly shorter median overall survival (14 vs 43 months; P =.01) and was significantly correlated with CD10 positivity (odds ratio 5.11; P =.0000286) and a higher Ki67 index (P =.0094).

Study details: The data come from a systematic review and meta-analysis of 10 studies that involved 102 patients with MCL and reported BCL6- and CD10-positive or -negative MCL and Ki67% in BCL6-positive or -negative MCL.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Source: Castillo DR et al. Unveiling the prognostic significance of BCL6+/CD10+ mantle cell lymphoma: Meta-analysis of individual patients and systematic review. Int J Mol Sci. 2023;24(12):10207 (Jun 16). Doi: 10.3390/ijms241210207

Key clinical point: BCL6 positivity is associated with worse survival outcomes and a higher Ki67 index and shows a positive correlation with CD10 positivity in patients with mantle cell lymphoma (MCL).

Major finding: A positive vs negative expression of BCL6 was associated with a significantly shorter median overall survival (14 vs 43 months; P =.01) and was significantly correlated with CD10 positivity (odds ratio 5.11; P =.0000286) and a higher Ki67 index (P =.0094).

Study details: The data come from a systematic review and meta-analysis of 10 studies that involved 102 patients with MCL and reported BCL6- and CD10-positive or -negative MCL and Ki67% in BCL6-positive or -negative MCL.

Disclosures: This study received no external funding. The authors declared no conflicts of interest.

Source: Castillo DR et al. Unveiling the prognostic significance of BCL6+/CD10+ mantle cell lymphoma: Meta-analysis of individual patients and systematic review. Int J Mol Sci. 2023;24(12):10207 (Jun 16). Doi: 10.3390/ijms241210207

Key clinical point: Among patients receiving the bendamustine-rituximab regimen for newly diagnosed mantle cell lymphoma (MCL), selected patients with high-risk disease may require CD19-directed autologous chimeric antigen receptor-T cell therapy within 6 months of bendamustine exposure.

Major finding: The cumulative incidences of the first and second MCL progression were 14% (95% CI 8%-20%) and 6% (95% CI 3%-11%), respectively, at 6 months from the last bendamustine dose. Ki67 ≥ 50% was a significant risk factor for the occurrence of the first MCL progression within 6 months of bendamustine exposure (adjusted sub-hazard ratio 3.38; P =.022).

Study details: Findings are from retrospective population-based study including 118 adult patients with newly diagnosed MCL who received bendamustine-rituximab induction therapy with or without high-dose cytarabine and autologous stem cell transplantation followed by maintenance rituximab therapy.

Disclosures: This study did not receive any funding. All authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Estimating the impact of early bendamustine failure on feasibility of subsequent CAR-T cell therapy in mantle cell lymphoma. Leuk Lymphoma. 2023 (Jun 20). Doi: 10.1080/10428194.2023.2226278

Key clinical point: Among patients receiving the bendamustine-rituximab regimen for newly diagnosed mantle cell lymphoma (MCL), selected patients with high-risk disease may require CD19-directed autologous chimeric antigen receptor-T cell therapy within 6 months of bendamustine exposure.

Major finding: The cumulative incidences of the first and second MCL progression were 14% (95% CI 8%-20%) and 6% (95% CI 3%-11%), respectively, at 6 months from the last bendamustine dose. Ki67 ≥ 50% was a significant risk factor for the occurrence of the first MCL progression within 6 months of bendamustine exposure (adjusted sub-hazard ratio 3.38; P =.022).

Study details: Findings are from retrospective population-based study including 118 adult patients with newly diagnosed MCL who received bendamustine-rituximab induction therapy with or without high-dose cytarabine and autologous stem cell transplantation followed by maintenance rituximab therapy.

Disclosures: This study did not receive any funding. All authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Estimating the impact of early bendamustine failure on feasibility of subsequent CAR-T cell therapy in mantle cell lymphoma. Leuk Lymphoma. 2023 (Jun 20). Doi: 10.1080/10428194.2023.2226278

Key clinical point: Among patients receiving the bendamustine-rituximab regimen for newly diagnosed mantle cell lymphoma (MCL), selected patients with high-risk disease may require CD19-directed autologous chimeric antigen receptor-T cell therapy within 6 months of bendamustine exposure.

Major finding: The cumulative incidences of the first and second MCL progression were 14% (95% CI 8%-20%) and 6% (95% CI 3%-11%), respectively, at 6 months from the last bendamustine dose. Ki67 ≥ 50% was a significant risk factor for the occurrence of the first MCL progression within 6 months of bendamustine exposure (adjusted sub-hazard ratio 3.38; P =.022).

Study details: Findings are from retrospective population-based study including 118 adult patients with newly diagnosed MCL who received bendamustine-rituximab induction therapy with or without high-dose cytarabine and autologous stem cell transplantation followed by maintenance rituximab therapy.

Disclosures: This study did not receive any funding. All authors declared receiving honoraria from various sources.

Source: Puckrin R et al. Estimating the impact of early bendamustine failure on feasibility of subsequent CAR-T cell therapy in mantle cell lymphoma. Leuk Lymphoma. 2023 (Jun 20). Doi: 10.1080/10428194.2023.2226278

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