B-Cell Lymphoma ICYMI

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

Key clinical point: Chimeric antigen receptor (CAR)-T cell therapy after lymphodepletion led to similar survival outcomes and toxicity rates in patients with nodal (ND) and extra nodal (EN) diffuse large B-cell lymphoma (DLBCL), with outcomes being significantly worse in patients with >2 vs <3 EN sites at lymphodepletion.

Major finding: After a median follow-up of 7.5 months, patients with EN and ND DLBCL had similar median progression-free survival (PFS; 10.76 and 14.1 months, respectively; P  =  .126), overall survival (OS; 15.36 and 18.4 months, respectively; P  =  .100), and treatment-related toxicity rates. Patients with <3 vs >2 EN sites had significantly longer median PFS (P  =  .01) and OS (P  =  .05).

Study details: This real-world retrospective multicenter study included 126 patients with DLBCL of EN (n = 72) or ND (n = 42) origin who underwent lymphodepletion followed by CAR-T cell infusion with tisagenlecleucel or axicabtagene ciloleucel.

Disclosures: No information on the source of funding was provided. The authors declared no conflicts of interest.

Source: Katz OB et al. Response rates of extra-nodal diffuse large B cell lymphoma to anti CD19-CAR T cells: A real word retrospective multi-center study. Eur J Haematol. 2023 (Mar 25). Doi: 10.1111/ejh.13968

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

Key clinical point: Sufficiently fit older patients with high-risk diffuse large B-cell lymphoma (DLBCL) achieve favorable outcomes with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R); patients with a poor performance status (PS) develop unacceptable toxicity and require less intensive therapy.

Major finding: At 3 years, the progression-free survival (PFS) and overall survival (OS) rates were 53% and 58%, respectively, and the treatment-related mortality (TRM) rate was 13%. The 3-year PFS (58% vs 32%; P < .001) and OS (64% vs 33%; P  =  .007) rates were significantly higher and TRM rates were significantly lower (6% vs 43%; P < .001) among patients with PS 0-2 vs 3-4.

Study details: This multicenter retrospective real-life study included 120 patients aged ≥60 years with newly diagnosed high-risk DLBCL treated with a median of 6 DA-EPOCH-R cycles per patient.

Disclosures: No information on the source of funding or conflicts of interest was provided.

Source: Mitrovic Z et al. Dose-adjusted EPOCH and rituximab (DA-EPOCH-R) in older patients with high-risk aggressive diffuse large B-cell lymphoma: A real-life multicenter study by the Croatian Cooperative Group for Hematologic diseases (KroHem). Eur J Haematol. 2023 (Mar 20). Doi: 10.1111/ejh.13957

Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

Key clinical point: Axicabtagene ciloleucel (axi-cel) is an effective second-line curative-intent therapy with a manageable safety profile for patients aged ≥65 years with relapsed or refractory large B-cell lymphoma (LBCL).

Major finding: At a median follow-up of 24.3 months, the median event-free survival was significantly longer with axi-cel vs standard of care (SOC; 21.5 vs 2.5 months; hazard ratio 0.276; descriptive P < .0001). The grade ≥3 treatment-emergent adverse event rates were 94% and 82% with axi-cel and SOC, respectively.

Study details: Findings are from a preplanned analysis of 109 patients aged ≥65 years with relapsed or refractory LBCL from the ZUMA-7 trial who were randomly assigned to receive second-line axi-cel (n = 51) or SOC (n = 58; 2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation).

Disclosures: This study was supported by Kite, a Gilead Company. Some authors reported ties with various organizations, including Kite and Gilead.

Source: Westin JR et al. Safety and efficacy of axicabtagene ciloleucel versus standard of care in patients 65 years of age or older with relapsed/refractory large B-cell lymphoma. Clin Cancer Res. 2023 (Mar 31). Doi: 10.1158/1078-0432.CCR-22-3136

Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

Key clinical point: The addition of venetoclax to lenalidomide plus rituximab therapy may provide an effective and safe combination for the treatment of unselected patients with untreated mantle cell lymphoma (MCL).

Major finding: All patients were escalated to the maximum tolerated dose of venetoclax (400 mg daily). The overall response and complete remission rates were 96% and 86%, respectively. After a median follow-up of 27.5 months, the median overall survival and progression-free survival were not reached. No dose-limiting toxicity event was observed.

Study details: This multicenter phase 1 study included 28 unselected adult patients with untreated MCL who received induction therapy with lenalidomide (daily on days 1-21 of each cycle), rituximab (weekly during cycle 1 until cycle 2 day 1), and venetoclax (escalated weekly up to 400 mg daily) for 6-12 cycles followed by maintenance therapy.

Disclosures: This study was funded by AbbVie and the University of Michigan Rogel Cancer Center. Some authors reported ties with various organizations, including AbbVie.

Source: Phillips TJ et al. Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Blood Adv. 2023 (Apr 4). Doi: 10.1182/bloodadvances.2023009992

Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

Key clinical point: Compared with matched control individuals, patients with mantle cell lymphoma (MCL) treated with or without high-dose chemotherapy with autologous stem cell transplantation (HD-ASCT) had higher hospitalization rates and relative risks for blood disorders and infections.

Major finding: Patients with MCL vs control individuals had a significantly increased incidence rate of outpatient (incidence rate ratio [IRR] 2.0; 95% CI 1.8-2.2) and inpatient (IRR 7.2; 95% CI 6.3-8.3) visits and relative risks for blood disorders (non-HD-ASCT: hazard ratio [HR] 9.84; 95% CI 6.91-14.00; HD-ASCT: HR 5.80; 95% CI 3.42-9.84) and infections (non-HD-ASCT: HR 4.66; 95% CI 3.62-5.99; HD-ASCT: HR 5.62; 95% CI 4.20-7.52).

Study details: Findings are from a population-based study including 620 adult patients with MCL who did (n = 247) or did not (n = 373) receive HD-ASCT and 6200 matched control individuals without MCL.

Disclosures: This study was supported by the Swedish Cancer Society. The authors reported ties with various organizations.

Source: Ekberg S et al. Late effects in patients with mantle cell lymphoma treated with or without autologous stem cell transplantation. Blood Adv. 2023;7(5):866-874 (Mar 14). Doi: 10.1182/bloodadvances.2022007241

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

Key clinical point: Compared with bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), ibrutinib plus bendamustine and rituximab (Ibru+BR) prolongs progression-free survival (PFS) in patients with newly diagnosed mantle cell lymphoma (MCL) who are ineligible for intensive therapy.

Major finding: Ibru+BR significantly improved PFS compared with VR-CAP (hazard ratio [HR] 0.55; P  =  .03) and R-CHOP (HR 0.35; P < .001). Adverse event risks were not significantly different in the Ibru+BR, VR-CAP, R-CHOP, and BR treatment arms.

Study details: The data come from a network meta-analysis of 3 studies involving 1459 patients with newly diagnosed MCL who were ineligible for intensive therapy and received first-line Ibru+BR, VR-CAP, R-CHOP, or BR.

Disclosures: This study did not report the source of funding. The authors declared no conflicts of interest.

Source: Sheng Z and Wang L. Superiority of ibrutinib plus bendamustine and rituximab in newly diagnosed patients with mantle-cell lymphoma ineligible for intensive therapy: A network meta-analysis. Eur J Haematol. 2023 (Mar 14). Doi: 10.1111/ejh.13953

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

Key clinical point: Compared with chemoimmunotherapy, second-line targeted therapies improved treatment-free survival (TFS) and tended to improve overall survival (OS) in patients with chronic lymphocytic leukemia (CLL), including those who were frail and had comorbidities.

Major finding: The 3-year TFS and estimated OS rates were higher in patients receiving targeted therapies (63%, 95% CI 50%-76%; and 79%, 95% CI 68%-91%, respectively) vs fludarabine, cyclophosphamide, and rituximab or bendamustine and rituximab (FCR/BR; 37%,; 95% CI 26%-48%; and 70%, 95% CI 60%-81%, respectively) or chlorambucil+/−CD20-antibody (CD20Clb/Clb; 22%, 95% CI 10%-33%; and 60%, 95% CI 47%-74%, respectively). The grade ≥3 adverse event rate was similar with targeted treatment and FCR/BR.

Study details: This retrospective population-based real-world study included 286 patients with CLL who relapsed or were refractory to first-line treatment and received second-line targeted treatment (ibrutinib+venetoclax, venetoclax, venetoclax+rituximab/obinutuzumab, idelalisib, or idelalisib+rituximab), FCR/BR, or CD20Clb/Clb.

Disclosures: This study was partly supported by grants from Rigshospitalets Foundation. Some authors reported ties with various sources.

Source: Vainer N et al. Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia. Br J Haematol. 2023 (Mar 10). Doi: 10.1111/bjh.18715

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

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

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

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

Ibrutinib (Imbruvica) quickly changed the treatment of chronic lymphocytic leukemia after it launched in 2013 as the first Bruton tyrosine kinase inhibitor and went on to become a bestselling drug in the United States. However, not even the availability of newer treatment options has reduced the price or the rate of prescribing ibrutinib.

In fact, the opposite has been seen: Both the price and prescribing of ibrutinib have increased markedly from 2014 to 2020, the authors of a new study say. The estimated net spending for a 30-day supply of ibrutinib increased by 46% during that period, despite the entry of several less costly and comparable products into the marketplace.

“Further research is needed to understand why oncologists have not embraced clinically superior options for CLL being sold at prices similar to, if not lower than, ibrutinib,” write the authors, led by Edward Scheffer Cliff, MBBS, MPH, from the division of pharmacoepidemiology and pharmacoeconomics, Brigham and Women’s Hospital, Boston.

The study was published online (2023 Apr 7. doi: 10.1001/jamanetworkopen.2023.7467) as a research letter in JAMA Network Open.

Ibrutinib is currently indicated for the treatment of mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), Waldenström’s macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic graft versus host disease. Among the top-selling drugs in the United States, ibrutinib sales by 2020 accounted for more than $2.8 billion in annual net Medicare spending.

However, since ibrutinib’s launch in 2013, there have been several new drugs approved for use in CLL, the authors note. They include acalabrutinib (Calquence), also a BTK inhibitor but associated with fewer adverse events, and venetoclax (Venclexta), the first-in-class B-cell lymphoma-2 inhibitor that offers additional clinical advantages such as time-limited therapy and the potential for complete remission. In addition, phosphatidylinositol-3 kinase inhibitors (PI3K inhibitors) were also approved for CLL, but they are less effective and associated with higher toxicity and are usually reserved for patients who relapse multiple times.
 

Prescribing and cost increased

With the emergence of several new oral targeted drugs for CLL, the authors hypothesized that this might lower costs as a result of competition and affect overall spending on ibrutinib.

To test their theory, they analyzed trends in Medicare Part D use and spending on these drugs from 2014 to 2020 to determine annual spending on oral CLL drugs, the number of beneficiaries who received these drugs, and the average spending per 30-day fill.

A total of six oral medications were included in their analysis: three BTK inhibitors (ibrutinib, acalabrutinib, and zanubrutinib), two PI3K inhibitors (idelalisib and duvelisib), and one B-cell lymphoma-2 inhibitor (venetoclax).

During the study period, annual net Medicare spending for all six of these drugs and across all indications increased from $254 million to $3.7 billion.

At the start of the study period in 2014, 6,180 Medicare beneficiaries were being treated with ibrutinib, and this number dramatically increased to 26,847 beneficiaries in 2020. Spending on ibrutinib constituted more than three-quarters (77%) of the total Medicare costs for these six drugs in 2020.

The estimated net spending for a 30-day supply of ibrutinib rose by 46%, from $8,206 in 2014 to $11,980 in 2020, despite the entry of the competitor drugs into the marketplace, some of which also had lower price tags: venetoclax in 2016 (2020 30-day fill price, $7,787), acalabrutinib in 2017 ($11,428) and zanubrutinib in 2020 ($12,521).

In addition, a sensitivity analysis showed a similar trend outside of the Medicare system.

Unlike for ibrutinib, net spending for other oral targeted drugs generally did not increase over time, and some drug prices even dropped slightly.

The authors note that one limitation of their study is that Medicare does not report spending by indication, so it was unknown what proportion of the cost was for CLL as opposed to the other B-cell lymphomas.

“Brand-to-brand competition may have been ineffective at lowering Medicare costs due to lags between approval and change in prescriber practices, constraints on payers’ ability to effectively use formularies to negotiate prices, and financial incentives that can encourage intermediaries such as pharmacy benefit managers to accept high prices,” they conclude.

This study was supported by a grant from Arnold Ventures. Several of the authors have reported relationships with industry.

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

The latest therapies for chronic lymphocytic leukemia (CLL) offer prolonged remission, along with a need for better tools to gauge their effectiveness. Data from a new study published in Frontiers in Oncology demonstrate that assessing measurable residual disease (MRD) helps doctors evaluate and implement novel treatments.

“MRD measurement is now a key feature of CLL clinical trials reporting. It can change CLL care by enabling approval of medication use in the wider (nontrial) patient population based on MRD data, without having to wait (ever-increasing) times for conventional trial outcomes, such as progression-free survival [PFS],” said study author Tahla Munir MD, of the department of hematology, at the Leeds (England) Teaching Hospitals of the National Health Service Trust.

courtesy of NHS

“It also has potential to direct our treatment duration and follow-up strategies based on MRD results taken during or at the end of treatment, and to direct new treatment strategies, such as intermittent (as opposed to fixed-duration or continuous) treatment,” Dr. Munir said in an interview.

The review study defined MRD according to the detectable proportion of residual CLL cells. (Current international consensus for undetectable is U-MRD4 1 leukemic cell in 10,000 leukocytes.) The advantages and disadvantages of different MRD assays were analyzed. Multiparameter flow cytometry, an older technology, proved less sensitive to newer tests. It is reliable measuring to a sensitivity of U-MRD4 and more widely available than next-generation real-time quantitative polymerase chain reaction tests (NG-PCR).

“NG-PCR has the most potential for use in laboratory practice. It doesn’t require patient-specific primers and can detect around 1 CLL cell in 1x10⁶ leukocytes. The biggest challenge is laboratory sequencing and bioinformatic capacity,” said lead study author Amelia Fisher, clinical research fellow at the division of cancer studies and pathology, University of Leeds.

“Multiple wells are required to gather adequate data to match the sensitivity of NGS. As this technology improves to match NGS sensitivity using fewer wells, once primers (bespoke to each patient) are designed it will provide a simple to use, rapid and easily reportable MRD tool, that could be scaled up in the event of MRD testing becoming routine practice,” explained Dr. Fisher.

The study also demonstrated how MRD can offer more in-depth insights into the success of treatments versus PFS. In the MURANO clinical trial, which compared venetoclax-rituximab treatment with standard chemoimmunotherapy (SC) to treat relapsed or refractory CLL, the PFS and overall survival (OS) remained significantly prolonged in the VR group at 5 years after therapy.

Analysis of MRD levels in the VR arm demonstrated that those with U-MRD4 had superior OS, with survival at 5 years of 95.3%, compared with those with higher rates of MRD (72.9%). A slower rate of MRD doubling time in the VR-treated patients, compared with the SC-treated patients, also buttressed the notion of moving from SC to VR treatment for the general CLL patient population.

Researchers cautioned that “a lot of the data is very recent, and therefore we do not have conventional trial outcomes, e.g., PFS and OS for all the studies. Some of the data we have is over a relatively short time period.”

University of Texas MD Anderson Cancer Center

An independent expert not associated with the study, Alessandra Ferrajoli, MD, associate medical director of the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston, expressed agreement with the study’s main findings.

“It is very likely that MRD assessment will be incorporated as a standard measurement of treatment efficacy in patients with CLL in the near future. The technologies have evolved to high levels of sensitivity, and the methods are being successfully harmonized and standardized,” she said.

Neither the study authors nor Dr. Ferrajoli reported conflicts of interest.

The latest therapies for chronic lymphocytic leukemia (CLL) offer prolonged remission, along with a need for better tools to gauge their effectiveness. Data from a new study published in Frontiers in Oncology demonstrate that assessing measurable residual disease (MRD) helps doctors evaluate and implement novel treatments.

“MRD measurement is now a key feature of CLL clinical trials reporting. It can change CLL care by enabling approval of medication use in the wider (nontrial) patient population based on MRD data, without having to wait (ever-increasing) times for conventional trial outcomes, such as progression-free survival [PFS],” said study author Tahla Munir MD, of the department of hematology, at the Leeds (England) Teaching Hospitals of the National Health Service Trust.

courtesy of NHS

“It also has potential to direct our treatment duration and follow-up strategies based on MRD results taken during or at the end of treatment, and to direct new treatment strategies, such as intermittent (as opposed to fixed-duration or continuous) treatment,” Dr. Munir said in an interview.

The review study defined MRD according to the detectable proportion of residual CLL cells. (Current international consensus for undetectable is U-MRD4 1 leukemic cell in 10,000 leukocytes.) The advantages and disadvantages of different MRD assays were analyzed. Multiparameter flow cytometry, an older technology, proved less sensitive to newer tests. It is reliable measuring to a sensitivity of U-MRD4 and more widely available than next-generation real-time quantitative polymerase chain reaction tests (NG-PCR).

“NG-PCR has the most potential for use in laboratory practice. It doesn’t require patient-specific primers and can detect around 1 CLL cell in 1x10⁶ leukocytes. The biggest challenge is laboratory sequencing and bioinformatic capacity,” said lead study author Amelia Fisher, clinical research fellow at the division of cancer studies and pathology, University of Leeds.

“Multiple wells are required to gather adequate data to match the sensitivity of NGS. As this technology improves to match NGS sensitivity using fewer wells, once primers (bespoke to each patient) are designed it will provide a simple to use, rapid and easily reportable MRD tool, that could be scaled up in the event of MRD testing becoming routine practice,” explained Dr. Fisher.

The study also demonstrated how MRD can offer more in-depth insights into the success of treatments versus PFS. In the MURANO clinical trial, which compared venetoclax-rituximab treatment with standard chemoimmunotherapy (SC) to treat relapsed or refractory CLL, the PFS and overall survival (OS) remained significantly prolonged in the VR group at 5 years after therapy.

Analysis of MRD levels in the VR arm demonstrated that those with U-MRD4 had superior OS, with survival at 5 years of 95.3%, compared with those with higher rates of MRD (72.9%). A slower rate of MRD doubling time in the VR-treated patients, compared with the SC-treated patients, also buttressed the notion of moving from SC to VR treatment for the general CLL patient population.

Researchers cautioned that “a lot of the data is very recent, and therefore we do not have conventional trial outcomes, e.g., PFS and OS for all the studies. Some of the data we have is over a relatively short time period.”

University of Texas MD Anderson Cancer Center

An independent expert not associated with the study, Alessandra Ferrajoli, MD, associate medical director of the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston, expressed agreement with the study’s main findings.

“It is very likely that MRD assessment will be incorporated as a standard measurement of treatment efficacy in patients with CLL in the near future. The technologies have evolved to high levels of sensitivity, and the methods are being successfully harmonized and standardized,” she said.

Neither the study authors nor Dr. Ferrajoli reported conflicts of interest.

The latest therapies for chronic lymphocytic leukemia (CLL) offer prolonged remission, along with a need for better tools to gauge their effectiveness. Data from a new study published in Frontiers in Oncology demonstrate that assessing measurable residual disease (MRD) helps doctors evaluate and implement novel treatments.

“MRD measurement is now a key feature of CLL clinical trials reporting. It can change CLL care by enabling approval of medication use in the wider (nontrial) patient population based on MRD data, without having to wait (ever-increasing) times for conventional trial outcomes, such as progression-free survival [PFS],” said study author Tahla Munir MD, of the department of hematology, at the Leeds (England) Teaching Hospitals of the National Health Service Trust.

courtesy of NHS

“It also has potential to direct our treatment duration and follow-up strategies based on MRD results taken during or at the end of treatment, and to direct new treatment strategies, such as intermittent (as opposed to fixed-duration or continuous) treatment,” Dr. Munir said in an interview.

The review study defined MRD according to the detectable proportion of residual CLL cells. (Current international consensus for undetectable is U-MRD4 1 leukemic cell in 10,000 leukocytes.) The advantages and disadvantages of different MRD assays were analyzed. Multiparameter flow cytometry, an older technology, proved less sensitive to newer tests. It is reliable measuring to a sensitivity of U-MRD4 and more widely available than next-generation real-time quantitative polymerase chain reaction tests (NG-PCR).

“NG-PCR has the most potential for use in laboratory practice. It doesn’t require patient-specific primers and can detect around 1 CLL cell in 1x10⁶ leukocytes. The biggest challenge is laboratory sequencing and bioinformatic capacity,” said lead study author Amelia Fisher, clinical research fellow at the division of cancer studies and pathology, University of Leeds.

“Multiple wells are required to gather adequate data to match the sensitivity of NGS. As this technology improves to match NGS sensitivity using fewer wells, once primers (bespoke to each patient) are designed it will provide a simple to use, rapid and easily reportable MRD tool, that could be scaled up in the event of MRD testing becoming routine practice,” explained Dr. Fisher.

The study also demonstrated how MRD can offer more in-depth insights into the success of treatments versus PFS. In the MURANO clinical trial, which compared venetoclax-rituximab treatment with standard chemoimmunotherapy (SC) to treat relapsed or refractory CLL, the PFS and overall survival (OS) remained significantly prolonged in the VR group at 5 years after therapy.

Analysis of MRD levels in the VR arm demonstrated that those with U-MRD4 had superior OS, with survival at 5 years of 95.3%, compared with those with higher rates of MRD (72.9%). A slower rate of MRD doubling time in the VR-treated patients, compared with the SC-treated patients, also buttressed the notion of moving from SC to VR treatment for the general CLL patient population.

Researchers cautioned that “a lot of the data is very recent, and therefore we do not have conventional trial outcomes, e.g., PFS and OS for all the studies. Some of the data we have is over a relatively short time period.”

University of Texas MD Anderson Cancer Center

An independent expert not associated with the study, Alessandra Ferrajoli, MD, associate medical director of the department of leukemia at the University of Texas MD Anderson Cancer Center, Houston, expressed agreement with the study’s main findings.

“It is very likely that MRD assessment will be incorporated as a standard measurement of treatment efficacy in patients with CLL in the near future. The technologies have evolved to high levels of sensitivity, and the methods are being successfully harmonized and standardized,” she said.

Neither the study authors nor Dr. Ferrajoli reported conflicts of interest.

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that is clinically heterogeneous, ranging from indolent to aggressive in nature. As with other subtypes of NHL, the treatment landscape is rapidly evolving.

Chemoimmunotherapy remains the standard first-line therapy for younger, fit patients. Although multiple induction regimens are used in this setting, it is typical to use a cytarabine-containing approach. Recently, the long-term analysis of the MCL Younger trial continued to demonstrate improved outcomes with this strategy.¹ This phase 3 study included 497 patients aged ≥ 18 to < 66 years with previously untreated MCL who were randomly assigned to R-CHOP (cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine; n = 249) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin; n = 248). After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer time to treatment failure (hazard ratio [HR] 0.59; P = .038) and overall survival (Mantle Cell Lymphoma International Prognostic Index + Ki-67–adjusted HR 0.60; P = .0066).

Following chemoimmunotherapy, treatment for this patient population typically consists of consolidation with autologous stem cell transplantation (ASCT) and maintenance rituximab.² Recently, the role of ASCT has been called into question.³ Preliminary data from the phase 3 TRIANGLE study demonstrated improvement in outcomes when the Bruton tyrosine kinase (BTK) inhibitor ibrutinib was added to chemoimmunotherapy, regardless of whether patients received ASCT.⁴ Additional studies evaluating the role of transplantation, particularly among patients who are minimal residual disease negative after chemoimmunotherapy, are ongoing (NCT03267433).

Options continue to expand in the relapsed/refractory setting. The chimeric antigen receptor (CAR) T-cell therapy, brexucabtagene autoleucel (brexu-cel), was approved by the US Food and Drug Administration for relapsed/refractory MCL on the basis of the results of the ZUMA-2 study.⁵ Recently, a multicenter, retrospective study demonstrated promising efficacy in the real world as well (Wang et al). This study was performed across 16 medical centers and included 189 patients with relapsed/refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion. Of all patients receiving leukapheresis, 149 (79%) would not have met the eligibility criteria for ZUMA-2. At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival (PFS) rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. This approach, however, was associated with significant toxicity, with a nonrelapse mortality rate of 9.1% at 1 year, primarily because of infections. The grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively. Despite risks, this study confirms the role of CAR T-cell therapy for patients with relapsed/refractory MCL.

Other options in the relapsed setting include BTK and anti-apoptotic protein B-cell lymphoma (BCL-2) inhibitors. Although venetoclax, a BCL-2 inhibitor, has demonstrated activity in MCL in early-phase clinical trials, the role of this drug in clinical practice remains unclear.^6,7 A recent multicenter, retrospective study evaluated the use of venetoclax in 81 adult patients with relapsed/refractory MCL, most of whom were heavily pretreated (median of three prior treatments) and had high-risk features, including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents (Sawalha et al). In this study, venetoclax resulted in a good overall response rate (ORR) but short PFS. At a median follow-up of 16.4 months, patients had a median PFS and overall survival of 3.7 months (95% CI 2.3-5.6) and 12.5 months (95% CI 6.2-28.2), respectively, and an ORR of 40%. Studies of venetoclax in earlier lines of therapy and in combination with other agents are ongoing. There may also be a role for this treatment as a bridge to more definitive therapies, including CAR T-cell therapy or allogeneic stem cell transplantation. Other studies that are evaluating the role of bispecific antibodies and antibody drug conjugates are also underway, suggesting the potential for additional options in this patient population.

Additional References

1.         Hermine O, Jiang L, Walewski J, et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41:479-484. doi: 10.1200/JCO.22.01780

2.         Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260. doi: 10.1056/NEJMoa1701769

3.         Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554. doi: 10.1200/JCO.21.02698

4.         Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: Results from the randomized Triangle Trial by the European MCL Network. Blood. 2022;140(Suppl 1):1-3. doi: 10.1182/blood-2022-163018

5.         Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331-1342. doi: 10.1056/NEJMoa1914347

6.         Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35:826-833. doi: 10.1200/JCO.2016.70.4320

7.         Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378:1211-1223. doi: 10.1056/NEJMoa1715519

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that is clinically heterogeneous, ranging from indolent to aggressive in nature. As with other subtypes of NHL, the treatment landscape is rapidly evolving.

Chemoimmunotherapy remains the standard first-line therapy for younger, fit patients. Although multiple induction regimens are used in this setting, it is typical to use a cytarabine-containing approach. Recently, the long-term analysis of the MCL Younger trial continued to demonstrate improved outcomes with this strategy.¹ This phase 3 study included 497 patients aged ≥ 18 to < 66 years with previously untreated MCL who were randomly assigned to R-CHOP (cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine; n = 249) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin; n = 248). After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer time to treatment failure (hazard ratio [HR] 0.59; P = .038) and overall survival (Mantle Cell Lymphoma International Prognostic Index + Ki-67–adjusted HR 0.60; P = .0066).

Following chemoimmunotherapy, treatment for this patient population typically consists of consolidation with autologous stem cell transplantation (ASCT) and maintenance rituximab.² Recently, the role of ASCT has been called into question.³ Preliminary data from the phase 3 TRIANGLE study demonstrated improvement in outcomes when the Bruton tyrosine kinase (BTK) inhibitor ibrutinib was added to chemoimmunotherapy, regardless of whether patients received ASCT.⁴ Additional studies evaluating the role of transplantation, particularly among patients who are minimal residual disease negative after chemoimmunotherapy, are ongoing (NCT03267433).

Options continue to expand in the relapsed/refractory setting. The chimeric antigen receptor (CAR) T-cell therapy, brexucabtagene autoleucel (brexu-cel), was approved by the US Food and Drug Administration for relapsed/refractory MCL on the basis of the results of the ZUMA-2 study.⁵ Recently, a multicenter, retrospective study demonstrated promising efficacy in the real world as well (Wang et al). This study was performed across 16 medical centers and included 189 patients with relapsed/refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion. Of all patients receiving leukapheresis, 149 (79%) would not have met the eligibility criteria for ZUMA-2. At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival (PFS) rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. This approach, however, was associated with significant toxicity, with a nonrelapse mortality rate of 9.1% at 1 year, primarily because of infections. The grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively. Despite risks, this study confirms the role of CAR T-cell therapy for patients with relapsed/refractory MCL.

Other options in the relapsed setting include BTK and anti-apoptotic protein B-cell lymphoma (BCL-2) inhibitors. Although venetoclax, a BCL-2 inhibitor, has demonstrated activity in MCL in early-phase clinical trials, the role of this drug in clinical practice remains unclear.^6,7 A recent multicenter, retrospective study evaluated the use of venetoclax in 81 adult patients with relapsed/refractory MCL, most of whom were heavily pretreated (median of three prior treatments) and had high-risk features, including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents (Sawalha et al). In this study, venetoclax resulted in a good overall response rate (ORR) but short PFS. At a median follow-up of 16.4 months, patients had a median PFS and overall survival of 3.7 months (95% CI 2.3-5.6) and 12.5 months (95% CI 6.2-28.2), respectively, and an ORR of 40%. Studies of venetoclax in earlier lines of therapy and in combination with other agents are ongoing. There may also be a role for this treatment as a bridge to more definitive therapies, including CAR T-cell therapy or allogeneic stem cell transplantation. Other studies that are evaluating the role of bispecific antibodies and antibody drug conjugates are also underway, suggesting the potential for additional options in this patient population.

Additional References

1.         Hermine O, Jiang L, Walewski J, et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41:479-484. doi: 10.1200/JCO.22.01780

2.         Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260. doi: 10.1056/NEJMoa1701769

3.         Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554. doi: 10.1200/JCO.21.02698

4.         Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: Results from the randomized Triangle Trial by the European MCL Network. Blood. 2022;140(Suppl 1):1-3. doi: 10.1182/blood-2022-163018

5.         Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331-1342. doi: 10.1056/NEJMoa1914347

6.         Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35:826-833. doi: 10.1200/JCO.2016.70.4320

7.         Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378:1211-1223. doi: 10.1056/NEJMoa1715519

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin lymphoma (NHL) that is clinically heterogeneous, ranging from indolent to aggressive in nature. As with other subtypes of NHL, the treatment landscape is rapidly evolving.

Chemoimmunotherapy remains the standard first-line therapy for younger, fit patients. Although multiple induction regimens are used in this setting, it is typical to use a cytarabine-containing approach. Recently, the long-term analysis of the MCL Younger trial continued to demonstrate improved outcomes with this strategy.¹ This phase 3 study included 497 patients aged ≥ 18 to < 66 years with previously untreated MCL who were randomly assigned to R-CHOP (cyclophosphamide, doxorubicin, prednisone, rituximab, and vincristine; n = 249) or R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin; n = 248). After a median follow-up of 10.6 years, the R-DHAP vs R-CHOP arm continued to have a significantly longer time to treatment failure (hazard ratio [HR] 0.59; P = .038) and overall survival (Mantle Cell Lymphoma International Prognostic Index + Ki-67–adjusted HR 0.60; P = .0066).

Following chemoimmunotherapy, treatment for this patient population typically consists of consolidation with autologous stem cell transplantation (ASCT) and maintenance rituximab.² Recently, the role of ASCT has been called into question.³ Preliminary data from the phase 3 TRIANGLE study demonstrated improvement in outcomes when the Bruton tyrosine kinase (BTK) inhibitor ibrutinib was added to chemoimmunotherapy, regardless of whether patients received ASCT.⁴ Additional studies evaluating the role of transplantation, particularly among patients who are minimal residual disease negative after chemoimmunotherapy, are ongoing (NCT03267433).

Options continue to expand in the relapsed/refractory setting. The chimeric antigen receptor (CAR) T-cell therapy, brexucabtagene autoleucel (brexu-cel), was approved by the US Food and Drug Administration for relapsed/refractory MCL on the basis of the results of the ZUMA-2 study.⁵ Recently, a multicenter, retrospective study demonstrated promising efficacy in the real world as well (Wang et al). This study was performed across 16 medical centers and included 189 patients with relapsed/refractory MCL who underwent leukapheresis for commercial manufacturing of brexu-cel, of which 168 received brexu-cel infusion. Of all patients receiving leukapheresis, 149 (79%) would not have met the eligibility criteria for ZUMA-2. At a median follow-up of 14.3 months after infusion, the best overall and complete response rates were 90% and 82%, respectively. The 6- and 12-month progression-free survival (PFS) rates were 69% (95% CI 61%-75%) and 59% (95% CI 51%-66%), respectively. This approach, however, was associated with significant toxicity, with a nonrelapse mortality rate of 9.1% at 1 year, primarily because of infections. The grade ≥ 3 cytokine release syndrome and neurotoxicity rates were 8% and 32%, respectively. Despite risks, this study confirms the role of CAR T-cell therapy for patients with relapsed/refractory MCL.

Other options in the relapsed setting include BTK and anti-apoptotic protein B-cell lymphoma (BCL-2) inhibitors. Although venetoclax, a BCL-2 inhibitor, has demonstrated activity in MCL in early-phase clinical trials, the role of this drug in clinical practice remains unclear.^6,7 A recent multicenter, retrospective study evaluated the use of venetoclax in 81 adult patients with relapsed/refractory MCL, most of whom were heavily pretreated (median of three prior treatments) and had high-risk features, including high Ki-67 and TP53 alterations, who received venetoclax without (n = 50) or with (n = 31) other agents (Sawalha et al). In this study, venetoclax resulted in a good overall response rate (ORR) but short PFS. At a median follow-up of 16.4 months, patients had a median PFS and overall survival of 3.7 months (95% CI 2.3-5.6) and 12.5 months (95% CI 6.2-28.2), respectively, and an ORR of 40%. Studies of venetoclax in earlier lines of therapy and in combination with other agents are ongoing. There may also be a role for this treatment as a bridge to more definitive therapies, including CAR T-cell therapy or allogeneic stem cell transplantation. Other studies that are evaluating the role of bispecific antibodies and antibody drug conjugates are also underway, suggesting the potential for additional options in this patient population.

Additional References

1.         Hermine O, Jiang L, Walewski J, et al. High-dose cytarabine and autologous stem-cell transplantation in mantle cell lymphoma: Long-term follow-up of the randomized Mantle Cell Lymphoma Younger Trial of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2023;41:479-484. doi: 10.1200/JCO.22.01780

2.         Le Gouill S, Thieblemont C, Oberic L, et al. Rituximab after autologous stem-cell transplantation in mantle-cell lymphoma. N Engl J Med. 2017;377:1250-1260. doi: 10.1056/NEJMoa1701769

3.         Martin P, Cohen JB, Wang M, et al. Treatment outcomes and roles of transplantation and maintenance rituximab in patients with previously untreated mantle cell lymphoma: Results from large real-world cohorts. J Clin Oncol. 2023;41:541-554. doi: 10.1200/JCO.21.02698

4.         Dreyling M, Doorduijn JK, Gine E, et al. Efficacy and safety of ibrutinib combined with standard first-line treatment or as substitute for autologous stem cell transplantation in younger patients with mantle cell lymphoma: Results from the randomized Triangle Trial by the European MCL Network. Blood. 2022;140(Suppl 1):1-3. doi: 10.1182/blood-2022-163018

5.         Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-Cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382:1331-1342. doi: 10.1056/NEJMoa1914347

6.         Davids MS, Roberts AW, Seymour JF, et al. Phase I first-in-human study of venetoclax in patients with relapsed or refractory non-Hodgkin lymphoma. J Clin Oncol. 2017;35:826-833. doi: 10.1200/JCO.2016.70.4320

7.         Tam CS, Anderson MA, Pott C, et al. Ibrutinib plus venetoclax for the treatment of mantle-cell lymphoma. N Engl J Med. 2018;378:1211-1223. doi: 10.1056/NEJMoa1715519