Clinical Edge Journal Scan

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: High-dose cytarabine (HDAC)-based pre-autologous stem cell transplantation (ASCT) induction regimens were not associated with improved survival but led to higher overall response rates (ORR) and lower rates of early relapses in ASCT-eligible patients with mantle cell lymphoma (MCL).

Major finding: Patients receiving rituximab + HDAC (R-HDAC)-based regimens vs rituximab + cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) had significantly higher ORR (85.9% vs 65.7%; P = .007), lower 24-month progression rates (61.9% vs 80.4%; P = .043), and lower mortality (43.9% vs 68.6%; P = .004). However, the 2-year overall survival rates were similar between the R-HADC + ASCT and R-CHOP + ASCT groups (88.7% and 78.8%, respectively; P = .289).

Study details: This retrospective single-center study included 165 ASCT-eligible adult patients with MCL, of whom 136 patients received pre-ASCT induction immunochemotherapy with R-CHOP-like or regimens based on R-HDAC and 50 patients received consolidation with high-dose therapy and ASCT.

Disclosures: This study did not receive any specific funding. The authors declared no conflicts of interest.

Source: de Pádua Covas Lage LA et al. Up-front ASCT overcomes the survival benefit provided by HDAC-based induction regimens in mantle cell lymphoma: Data from a real-life and long-term cohort. Cancers. 2023; 15(19):4759 (Sep 28). doi: 10.3390/cancers15194759

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: Cumulative airborne dioxin exposure is significantly associated with an increased risk for non-Hodgkin's lymphoma (NHL), particularly for combined chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

Major finding: A significant association was observed between log-transformed cumulative dioxin exposure index scores and the risk for NHL (adjusted odds ratio [aOR] 1.2; 95% CI 1.0-1.4), especially in case of the CLL and SLL subtypes (aOR 1.6; 95% CI 1.1-2.3), for a 4.4 log µg-toxic equivalent quantity/m² increase corresponding to a standard deviation.

Study details: This case-control study was nested within the prospective French National Institute for Health and Medical Research E3N cohort and included 368 women with NHL and 368 matched control women without NHL.

Disclosures: The E3N cohort was established and maintained with the support of the Mutuelle Générale de l'Education Nationale, France, and other sources. The authors declared no conflicts of interest.

Source: Gaspard E et al. Association between cumulative airborne dioxin exposure and non-Hodgkin's lymphoma risk in a nested case-control study within the French E3N cohort. Sci Total Environ. 2023;906:167330 (Sep 29). doi: 10.1016/j.scitotenv.2023.167330

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: The ibrutinib + bortezomib combination shows durable efficacy and manageable safety in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL), including high-risk patients.

Major finding: The combination led to an objective response rate of 81.8% (90% CI 71.1%-89.8%), which increased to 87.3% (90% CI 77.4%-93.9%) with ibrutinib maintenance. At a 25.4-month median follow-up, the median duration of response and progression-free survival were 22.7 (95% CI 12.3-not achieved) and 18.6 (95% CI 12.5-not achieved) months, respectively. The adverse event profile was consistent with the known safety profiles of individual drugs.

Study details: This phase 2 trial included 55 ibrutinib-naive and bortezomib-naive patients with R/R MCL previously treated with ≤2 lines of chemotherapy (of whom 75.6% had ≥1 high-risk features) who received 6 cycles of ibrutinib + bortezomib followed by ibrutinib maintenance.

Disclosures: This study was supported by Janssen and others. Some authors declared serving on the advisory boards of or receiving research funding, consulting fees, honoraria, or meeting or travel support from various sources, including Janssen.

Source: Novak U et al. Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: A phase 1/2 trial of the European MCL network (SAKK 36/13). EClinicalMedicine. 2023;64:102221 (Sep 21). doi: 10.1016/j.eclinm.2023.102221

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Ibrutinib maintenance (I-M; dose 560 mg daily) for 4 years is effective in patients with treatment-naive mantle cell lymphoma (MCL) who are responsive to frontline chemo-immunotherapy with significant but manageable toxicities.

Major finding: The 3-year progression-free survival (PFS) and overall survival (OS) rates were 94% and 97%, whereas the 5-year PFS and OS rates were 89% and 91%, respectively. In patients with prior autologous stem cell transplantation (autoSCT), the 5-year PFS and OS rates were 100% each. The most common treatment-related adverse event was infection (86%; grades 1-2), and the most common grade 3-4 toxicities were hematologic.

Study details: This multicenter phase 2 study included patients with treatment-naive MCL who achieved a complete or partial response to frontline intensive induction chemo-immunotherapy with or without autoSCT and received 560 mg I-M daily for 4 years.

Disclosures: This study was supported by Pharmacyclics and Janssen. R Karmali and B Pro declared serving as consultants, speakers, or advisory board members for or receiving research funding or honoraria from various sources.

Source: Karmali R et al. Ibrutinib maintenance following frontline treatment in patients with mantle cell lymphoma. Blood Adv. 2023 (Sep 27). doi: 10.1182/bloodadvances.2023011271

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Prophylaxis with high-dose methotrexate (HD-MTX) was not associated with a clinically meaningful reduction in the risk for central nervous system (CNS) progression in high-risk patients with aggressive B-cell lymphoma (BCL).

Major finding: Patients who did vs did not receive HD-MTX had a significantly lower risk for CNS progression (adjusted 5-year risk difference 1.6%; adjusted hazard ratio [aHR] 0.59; P = .014), but the significance was lost when considering only those who achieved a complete response at chemoimmunotherapy completion (adjusted 5-year risk difference 1.4%; aHR 0.74; P = .30).

Study details: This multicenter retrospective study included 2418 adults with aggressive BCL and a high risk for CNS progression treated with curative-intent anti-CD20-based chemoimmunotherapy who did or did not receive HD-MTX, of whom 1616 achieved a complete response.

Disclosures: This study was funded by Janssen Pharmaceuticals and others. All authors except TC El-Galaly declared serving as consultants, advisors, or speakers for or receiving honoraria, research funding, or travel support from various sources, including Janssen.

Source: Lewis KL et al on behalf of the International CNS Prophylaxis Study Group. High-dose methotrexate as CNS prophylaxis in high-risk aggressive B-cell lymphoma. J Clin Oncol. 2023 (Oct 5). doi: 10.1200/JCO.23.00365

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line vs later-line zanubrutinib treatment leads to significantly improved long-term survival outcomes in patients with relapsed or refractory mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 35.2 months, patients receiving second-line vs later-line zanubrutinib had significantly improved median overall survival (adjusted hazard ratio 0.459; P = .044) and numerically longer median progression-free survival (27.8 vs 22.1 months). Adverse events observed in both groups were consistent with the known safety profile of zanubrutinib.

Study details: Findings are from an updated pooled analysis of 112 patients from the BGB-3111-AU-003 and BGB-3111-206 clinical trials who had relapsed or refractory MCL and received second-line (n = 41) or later-line (n = 71) zanubrutinib.

Disclosures: The BGB-3111-AU-003 and BGB-3111-206 trials were sponsored by BeiGene. C Fang and S Sun declared being employees of BeiGene Co., Ltd., China. The other authors declared no conflicts of interest.

Source: Song Y et al. Long-term outcomes of second-line versus later-line zanubrutinib treatment in patients with relapsed/refractory mantle cell lymphoma: An updated pooled analysis. Cancer Med. 2023;12(18):18643-18653 (Sep 14). doi: 10.1002/cam4.6473

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Key clinical point: Second-line axicabtagene ciloleucel (axi-cel) provides high response rates and manageable safety in patients with high-risk relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are ineligible for autologous stem-cell transplantation (ASCT).

Major finding: At 3 months from axi-cel infusion, the complete metabolic response rate was 71.0% (95% CI 58.1%-81.8%). At a 12-month median follow-up, the median progression-free survival was 11.8 months (95% CI 8.4-not reached) whereas median overall survival was not reached. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in 8.1% and 14.5% of patients, respectively.

Study details: Findings are from the phase 2 ALYCANTE trial including 62 ASCT-ineligible patients with high-risk R/R LBCL who underwent leukapheresis and subsequently received second-line axi-cel.

Disclosures: This study was funded by Kite, a Gilead company. Some authors declared serving as members of directors’ boards or advisory committees of or receiving honoraria, research funding, consulting fees, or travel or accommodation expenses from various sources, including Kite and Gilead.

Source: Houot R et al. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: A phase 2 trial. Nat Med. 2023;29:2593-2601 (Sep 14). doi: 10.1038/s41591-023-02572-5

Key clinical point: Comparable prevalence rates of non-alcoholic fatty liver disease (NAFLD) in patients with moderate-to-severe atopic dermatitis (AD) and those with in situ melanoma suggest that AD is not a risk factor for NAFLD.

Major finding: The prevalence rate of NAFLD was similar in patients with AD (24.1%) and those with in situ melanoma (23.2%), but it was significantly higher in patients with moderate-to-severe chronic plaque psoriasis (49.8%) compared with the other two groups (both P < .01). AD was not independently associated with NAFLD (adjusted odds ratio 1.02; 95% CI 0.78-1.26).

Study details: Findings are from a retrospective cross-sectional study including adult patients with moderate-to-severe AD (n = 144), moderate-to-severe chronic plaque psoriasis (n = 466), or in situ melanoma (n = 99).

Disclosures: This study was funded by European Union-Next Generation EU-NRRP M6C2-Investment 2.1 Enhancement and Strengthening of Biomedical Research in the National Health Service. The authors declared no conflicts of interest.

Source: Maurelli M et al. Prevalence of non-alcoholic fatty liver disease in adult individuals with moderate-to-severe atopic dermatitis. J Clin Med. 2023;12(18):6057 (Sep 19). doi: 10.3390/jcm12186057

Key clinical point: Comparable prevalence rates of non-alcoholic fatty liver disease (NAFLD) in patients with moderate-to-severe atopic dermatitis (AD) and those with in situ melanoma suggest that AD is not a risk factor for NAFLD.

Major finding: The prevalence rate of NAFLD was similar in patients with AD (24.1%) and those with in situ melanoma (23.2%), but it was significantly higher in patients with moderate-to-severe chronic plaque psoriasis (49.8%) compared with the other two groups (both P < .01). AD was not independently associated with NAFLD (adjusted odds ratio 1.02; 95% CI 0.78-1.26).

Study details: Findings are from a retrospective cross-sectional study including adult patients with moderate-to-severe AD (n = 144), moderate-to-severe chronic plaque psoriasis (n = 466), or in situ melanoma (n = 99).

Disclosures: This study was funded by European Union-Next Generation EU-NRRP M6C2-Investment 2.1 Enhancement and Strengthening of Biomedical Research in the National Health Service. The authors declared no conflicts of interest.

Source: Maurelli M et al. Prevalence of non-alcoholic fatty liver disease in adult individuals with moderate-to-severe atopic dermatitis. J Clin Med. 2023;12(18):6057 (Sep 19). doi: 10.3390/jcm12186057

Key clinical point: Comparable prevalence rates of non-alcoholic fatty liver disease (NAFLD) in patients with moderate-to-severe atopic dermatitis (AD) and those with in situ melanoma suggest that AD is not a risk factor for NAFLD.

Major finding: The prevalence rate of NAFLD was similar in patients with AD (24.1%) and those with in situ melanoma (23.2%), but it was significantly higher in patients with moderate-to-severe chronic plaque psoriasis (49.8%) compared with the other two groups (both P < .01). AD was not independently associated with NAFLD (adjusted odds ratio 1.02; 95% CI 0.78-1.26).

Study details: Findings are from a retrospective cross-sectional study including adult patients with moderate-to-severe AD (n = 144), moderate-to-severe chronic plaque psoriasis (n = 466), or in situ melanoma (n = 99).

Disclosures: This study was funded by European Union-Next Generation EU-NRRP M6C2-Investment 2.1 Enhancement and Strengthening of Biomedical Research in the National Health Service. The authors declared no conflicts of interest.

Source: Maurelli M et al. Prevalence of non-alcoholic fatty liver disease in adult individuals with moderate-to-severe atopic dermatitis. J Clin Med. 2023;12(18):6057 (Sep 19). doi: 10.3390/jcm12186057

Key clinical point: Long-term dupilumab treatment provides sustained clinical benefits and acceptable safety in children age 6-11 years with uncontrolled severe atopic dermatitis (AD).

Major finding: By week 52, 41% of patients achieved an Investigator’s Global Assessment score of 0 or 1, and 82% of patients achieved ≥75% improvement in the Eczema Area and Severity Index scores compared with the LIBERTY AD PEDS baseline. Treatment-emergent adverse events were mostly of mild or moderate severity.

Study details: This analysis of data from the LIBERTY AD PED-OLE study included 321 children (age 6-11 years) with severe AD who previously participated in LIBERTY AD PEDS and received 300 mg dupilumab every 4 weeks or an up-titrated weight-tiered dose of 200 or 300 mg dupilumab every 2 weeks.

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Seven authors declared being employees of or holding stocks or stock options in Sanofi or Regeneron. The other authors declared ties with various sources, including Sanofi and Regeneron.

Source: Cork MJ et al. Dupilumab safety and efficacy in a phase III open-label extension trial in children 6-11 years of age with severe atopic dermatitis. Dermatol Ther (Heidelb). 2023 (Sep 26). doi: 10.1007/s13555-023-01016-9

Key clinical point: Long-term dupilumab treatment provides sustained clinical benefits and acceptable safety in children age 6-11 years with uncontrolled severe atopic dermatitis (AD).

Major finding: By week 52, 41% of patients achieved an Investigator’s Global Assessment score of 0 or 1, and 82% of patients achieved ≥75% improvement in the Eczema Area and Severity Index scores compared with the LIBERTY AD PEDS baseline. Treatment-emergent adverse events were mostly of mild or moderate severity.

Study details: This analysis of data from the LIBERTY AD PED-OLE study included 321 children (age 6-11 years) with severe AD who previously participated in LIBERTY AD PEDS and received 300 mg dupilumab every 4 weeks or an up-titrated weight-tiered dose of 200 or 300 mg dupilumab every 2 weeks.

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Seven authors declared being employees of or holding stocks or stock options in Sanofi or Regeneron. The other authors declared ties with various sources, including Sanofi and Regeneron.

Source: Cork MJ et al. Dupilumab safety and efficacy in a phase III open-label extension trial in children 6-11 years of age with severe atopic dermatitis. Dermatol Ther (Heidelb). 2023 (Sep 26). doi: 10.1007/s13555-023-01016-9

Key clinical point: Long-term dupilumab treatment provides sustained clinical benefits and acceptable safety in children age 6-11 years with uncontrolled severe atopic dermatitis (AD).

Major finding: By week 52, 41% of patients achieved an Investigator’s Global Assessment score of 0 or 1, and 82% of patients achieved ≥75% improvement in the Eczema Area and Severity Index scores compared with the LIBERTY AD PEDS baseline. Treatment-emergent adverse events were mostly of mild or moderate severity.

Study details: This analysis of data from the LIBERTY AD PED-OLE study included 321 children (age 6-11 years) with severe AD who previously participated in LIBERTY AD PEDS and received 300 mg dupilumab every 4 weeks or an up-titrated weight-tiered dose of 200 or 300 mg dupilumab every 2 weeks.

Disclosures: This study was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Seven authors declared being employees of or holding stocks or stock options in Sanofi or Regeneron. The other authors declared ties with various sources, including Sanofi and Regeneron.

Source: Cork MJ et al. Dupilumab safety and efficacy in a phase III open-label extension trial in children 6-11 years of age with severe atopic dermatitis. Dermatol Ther (Heidelb). 2023 (Sep 26). doi: 10.1007/s13555-023-01016-9

Key clinical point: Tralokinumab led to clinically meaningful responses in adults with moderate-to-severe atopic dermatitis (AD) who failed to achieve an Investigator’s Global Assessment (IGA) score of 0 or 1 at 16 weeks without rescue medication.

Major finding: At week 16, a significantly greater proportion of patients receiving tralokinumab vs placebo achieved ≥ 50% improvement in the Eczema Area and Severity Index scores (33.0% vs 13.0%; P < .0001) and ≥ 3-point improvement in the itch Numerical Rating Scale scores (22.6% vs 9.4%; P < .0001).

Study details: This post hoc analysis of data from ECZTRA 1 and 2 trials included adults with moderate-to-severe AD who were randomized to receive tralokinumab (n = 966) or placebo (n = 362) and failed to achieve an IGA score of 0 or 1 at week 16 without rescue medication.

Disclosures: ECZTRA 1 and 2 were sponsored by LEO Pharma A/S, Denmark. Several authors declared ties with LEO Pharma, among others. T Mark declared being an employee and stockholder of LEO Pharma A/S.

Source: Simpson EL et al. Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1. Am J Clin Dermatol. 2023 (Oct 7). doi: 10.1007/s40257-023-00817-0

Key clinical point: Tralokinumab led to clinically meaningful responses in adults with moderate-to-severe atopic dermatitis (AD) who failed to achieve an Investigator’s Global Assessment (IGA) score of 0 or 1 at 16 weeks without rescue medication.

Major finding: At week 16, a significantly greater proportion of patients receiving tralokinumab vs placebo achieved ≥ 50% improvement in the Eczema Area and Severity Index scores (33.0% vs 13.0%; P < .0001) and ≥ 3-point improvement in the itch Numerical Rating Scale scores (22.6% vs 9.4%; P < .0001).

Study details: This post hoc analysis of data from ECZTRA 1 and 2 trials included adults with moderate-to-severe AD who were randomized to receive tralokinumab (n = 966) or placebo (n = 362) and failed to achieve an IGA score of 0 or 1 at week 16 without rescue medication.

Disclosures: ECZTRA 1 and 2 were sponsored by LEO Pharma A/S, Denmark. Several authors declared ties with LEO Pharma, among others. T Mark declared being an employee and stockholder of LEO Pharma A/S.

Source: Simpson EL et al. Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1. Am J Clin Dermatol. 2023 (Oct 7). doi: 10.1007/s40257-023-00817-0

Key clinical point: Tralokinumab led to clinically meaningful responses in adults with moderate-to-severe atopic dermatitis (AD) who failed to achieve an Investigator’s Global Assessment (IGA) score of 0 or 1 at 16 weeks without rescue medication.

Major finding: At week 16, a significantly greater proportion of patients receiving tralokinumab vs placebo achieved ≥ 50% improvement in the Eczema Area and Severity Index scores (33.0% vs 13.0%; P < .0001) and ≥ 3-point improvement in the itch Numerical Rating Scale scores (22.6% vs 9.4%; P < .0001).

Study details: This post hoc analysis of data from ECZTRA 1 and 2 trials included adults with moderate-to-severe AD who were randomized to receive tralokinumab (n = 966) or placebo (n = 362) and failed to achieve an IGA score of 0 or 1 at week 16 without rescue medication.

Disclosures: ECZTRA 1 and 2 were sponsored by LEO Pharma A/S, Denmark. Several authors declared ties with LEO Pharma, among others. T Mark declared being an employee and stockholder of LEO Pharma A/S.

Source: Simpson EL et al. Tralokinumab provides clinically meaningful responses at week 16 in adults with moderate-to-severe atopic dermatitis who do not achieve IGA 0/1. Am J Clin Dermatol. 2023 (Oct 7). doi: 10.1007/s40257-023-00817-0