B Cell Lymphoma

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

The treatment of mantle cell lymphoma (MCL) continues to evolve. In the front-line setting, studies are evaluating the role of novel therapies as well as consolidation with autologous stem cell transplantation. In the relapsed/refractory setting, patients can be considered for treatment with Bruton tyrosine kinase (BTK) inhibitors, other targeted therapies, or chimeric antigen receptor (CAR) T-cell therapy. Other novel therapies, including bispecific antibodies and novel antibody drug conjugates, are being studied as well.

Despite the availability of novel agents, a subset of patients continues to have difficult-to-treat disease and a poor prognosis. Established prognostic tools that aid in identifying high-risk patients include alternations in TP53, high proliferation rates, nonclassic morphology, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which incorporates age, performance status, lactate dehydrogenase levels, and white blood cell count. The Nordic study group recently published a paper which provides additional prognostic information beyond these known variables (Rodrigues et al). They examined MYC expression in a cohort of 251 patients with MCL and structural aberrations in MYC and MYC mRNA levels in a smaller cohort. They found that patients with tumors comprising 20% or more cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04), when adjusted for additional high-risk features. Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had a particularly poor prognosis, with significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of only 0.9 years (both P < .001). Though MYC overexpression was rare, this study identified a high-risk group of patients, especially those harboring concurrent TP53 aberrations, that may benefit from novel treatment approaches.

Another study recently aimed to identify patients who are at risk for poor outcomes after treatment with brexucabtagene autoleucel (brexu-cel) infusion. Though brexu-cel is an active therapy for patients with relapsed/refractory MCL, there are known toxicities, including cytokine release syndrome, neurologic toxicity, and hematologic toxicity. Given the potential for prolonged cytopenias and immune suppression, patients are also at risk for severe infections, which currently represent the driving determinant of nonrelapse mortality.¹ The CAR-HEMATOTOX (HT) score was previously found to identify patients who are at increased risk for hematologic toxicity after CAR T-cell therapy in diffuse large B-cell lymphoma.² In the current multicenter observational study, which included 103 patients receiving brexu-cel, the authors reported an association between baseline HT score and outcome in MCL as well. Patients with high (2-7) vs low (0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (aHR 3.7; P < .001) and overall (aHR 5.6; P = .002) survival. This tool may provide a helpful guide when counseling patients on treatment options and allow for more personalized toxicity management.

Despite availability of BTK inhibitors and CAR T-cell therapy for patients with MCL, relapses remain common. As upregulation of phosphoinositide 3-kinase (PI3K) is known to play a critical role in lymphomagenesis, there has been interest in targeting this pathway across lymphoma subtypes. Though PI3K inhibitors have been found to be active agents, they have also been associated with poor tolerability and safety concerns. Parsaclisib is a selective PI3K delta inhibitor that showed encouraging data in the phase 1/2 study in patients with non-Hodgkin lymphoma.³ More recently, the phase 2 CITADEL-205 study, which included adult patients with relapsed or refractory MCL previously treated with one to three systemic therapies, with (n = 53) or without (n = 108) prior BTK inhibitor treatment, was published (Zinazni et al). Patients received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily. Among BTK inhibitor–naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 months (95% CI 9.0 to not evaluable). Responses were not thought to be clinically meaningful in the patients treated with prior BTK inhibitors. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions. A total of 30% of patients required drug discontinuation due to adverse events. Though parsaclisib demonstrated activity in patients with relapsed/refractory MCL, the role of this drug in clinical practice is not clear given the increased use of BTK inhibitors as a preferred second-line therapy and ongoing concerns regarding PI3K inhibitor-related toxicity.

Additional References

1.      Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41:2594-2606. doi: 10.1200/JCO.22.01797

2.      Rejeski K, Perez A, Sesques P, et al. CAR-HEMATOTOX: A model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499-2513. doi: 10.1182/blood.2020010543

3.      Forero-Torres A, Ramchandren R, Yacoub A, et al. Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019;133:1742-1752. doi: 10.1182/blood-2018-08-867499

The treatment of mantle cell lymphoma (MCL) continues to evolve. In the front-line setting, studies are evaluating the role of novel therapies as well as consolidation with autologous stem cell transplantation. In the relapsed/refractory setting, patients can be considered for treatment with Bruton tyrosine kinase (BTK) inhibitors, other targeted therapies, or chimeric antigen receptor (CAR) T-cell therapy. Other novel therapies, including bispecific antibodies and novel antibody drug conjugates, are being studied as well.

Despite the availability of novel agents, a subset of patients continues to have difficult-to-treat disease and a poor prognosis. Established prognostic tools that aid in identifying high-risk patients include alternations in TP53, high proliferation rates, nonclassic morphology, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which incorporates age, performance status, lactate dehydrogenase levels, and white blood cell count. The Nordic study group recently published a paper which provides additional prognostic information beyond these known variables (Rodrigues et al). They examined MYC expression in a cohort of 251 patients with MCL and structural aberrations in MYC and MYC mRNA levels in a smaller cohort. They found that patients with tumors comprising 20% or more cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04), when adjusted for additional high-risk features. Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had a particularly poor prognosis, with significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of only 0.9 years (both P < .001). Though MYC overexpression was rare, this study identified a high-risk group of patients, especially those harboring concurrent TP53 aberrations, that may benefit from novel treatment approaches.

Another study recently aimed to identify patients who are at risk for poor outcomes after treatment with brexucabtagene autoleucel (brexu-cel) infusion. Though brexu-cel is an active therapy for patients with relapsed/refractory MCL, there are known toxicities, including cytokine release syndrome, neurologic toxicity, and hematologic toxicity. Given the potential for prolonged cytopenias and immune suppression, patients are also at risk for severe infections, which currently represent the driving determinant of nonrelapse mortality.¹ The CAR-HEMATOTOX (HT) score was previously found to identify patients who are at increased risk for hematologic toxicity after CAR T-cell therapy in diffuse large B-cell lymphoma.² In the current multicenter observational study, which included 103 patients receiving brexu-cel, the authors reported an association between baseline HT score and outcome in MCL as well. Patients with high (2-7) vs low (0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (aHR 3.7; P < .001) and overall (aHR 5.6; P = .002) survival. This tool may provide a helpful guide when counseling patients on treatment options and allow for more personalized toxicity management.

Despite availability of BTK inhibitors and CAR T-cell therapy for patients with MCL, relapses remain common. As upregulation of phosphoinositide 3-kinase (PI3K) is known to play a critical role in lymphomagenesis, there has been interest in targeting this pathway across lymphoma subtypes. Though PI3K inhibitors have been found to be active agents, they have also been associated with poor tolerability and safety concerns. Parsaclisib is a selective PI3K delta inhibitor that showed encouraging data in the phase 1/2 study in patients with non-Hodgkin lymphoma.³ More recently, the phase 2 CITADEL-205 study, which included adult patients with relapsed or refractory MCL previously treated with one to three systemic therapies, with (n = 53) or without (n = 108) prior BTK inhibitor treatment, was published (Zinazni et al). Patients received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily. Among BTK inhibitor–naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 months (95% CI 9.0 to not evaluable). Responses were not thought to be clinically meaningful in the patients treated with prior BTK inhibitors. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions. A total of 30% of patients required drug discontinuation due to adverse events. Though parsaclisib demonstrated activity in patients with relapsed/refractory MCL, the role of this drug in clinical practice is not clear given the increased use of BTK inhibitors as a preferred second-line therapy and ongoing concerns regarding PI3K inhibitor-related toxicity.

Additional References

1.      Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41:2594-2606. doi: 10.1200/JCO.22.01797

2.      Rejeski K, Perez A, Sesques P, et al. CAR-HEMATOTOX: A model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499-2513. doi: 10.1182/blood.2020010543

3.      Forero-Torres A, Ramchandren R, Yacoub A, et al. Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019;133:1742-1752. doi: 10.1182/blood-2018-08-867499

The treatment of mantle cell lymphoma (MCL) continues to evolve. In the front-line setting, studies are evaluating the role of novel therapies as well as consolidation with autologous stem cell transplantation. In the relapsed/refractory setting, patients can be considered for treatment with Bruton tyrosine kinase (BTK) inhibitors, other targeted therapies, or chimeric antigen receptor (CAR) T-cell therapy. Other novel therapies, including bispecific antibodies and novel antibody drug conjugates, are being studied as well.

Despite the availability of novel agents, a subset of patients continues to have difficult-to-treat disease and a poor prognosis. Established prognostic tools that aid in identifying high-risk patients include alternations in TP53, high proliferation rates, nonclassic morphology, and the Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which incorporates age, performance status, lactate dehydrogenase levels, and white blood cell count. The Nordic study group recently published a paper which provides additional prognostic information beyond these known variables (Rodrigues et al). They examined MYC expression in a cohort of 251 patients with MCL and structural aberrations in MYC and MYC mRNA levels in a smaller cohort. They found that patients with tumors comprising 20% or more cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04), when adjusted for additional high-risk features. Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had a particularly poor prognosis, with significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of only 0.9 years (both P < .001). Though MYC overexpression was rare, this study identified a high-risk group of patients, especially those harboring concurrent TP53 aberrations, that may benefit from novel treatment approaches.

Another study recently aimed to identify patients who are at risk for poor outcomes after treatment with brexucabtagene autoleucel (brexu-cel) infusion. Though brexu-cel is an active therapy for patients with relapsed/refractory MCL, there are known toxicities, including cytokine release syndrome, neurologic toxicity, and hematologic toxicity. Given the potential for prolonged cytopenias and immune suppression, patients are also at risk for severe infections, which currently represent the driving determinant of nonrelapse mortality.¹ The CAR-HEMATOTOX (HT) score was previously found to identify patients who are at increased risk for hematologic toxicity after CAR T-cell therapy in diffuse large B-cell lymphoma.² In the current multicenter observational study, which included 103 patients receiving brexu-cel, the authors reported an association between baseline HT score and outcome in MCL as well. Patients with high (2-7) vs low (0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (aHR 3.7; P < .001) and overall (aHR 5.6; P = .002) survival. This tool may provide a helpful guide when counseling patients on treatment options and allow for more personalized toxicity management.

Despite availability of BTK inhibitors and CAR T-cell therapy for patients with MCL, relapses remain common. As upregulation of phosphoinositide 3-kinase (PI3K) is known to play a critical role in lymphomagenesis, there has been interest in targeting this pathway across lymphoma subtypes. Though PI3K inhibitors have been found to be active agents, they have also been associated with poor tolerability and safety concerns. Parsaclisib is a selective PI3K delta inhibitor that showed encouraging data in the phase 1/2 study in patients with non-Hodgkin lymphoma.³ More recently, the phase 2 CITADEL-205 study, which included adult patients with relapsed or refractory MCL previously treated with one to three systemic therapies, with (n = 53) or without (n = 108) prior BTK inhibitor treatment, was published (Zinazni et al). Patients received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly or 2.5 mg parsaclisib once daily. Among BTK inhibitor–naive patients who received parsaclisib once daily, 70.1% (95% CI 58.6%-80.0%) and 15.6% (95% CI 8.3%-25.6%) achieved an objective response and a complete response, respectively, with the median duration of response being 12.1 months (95% CI 9.0 to not evaluable). Responses were not thought to be clinically meaningful in the patients treated with prior BTK inhibitors. Most treatment-emergent adverse events were low grade and manageable by dose interruptions or reductions. A total of 30% of patients required drug discontinuation due to adverse events. Though parsaclisib demonstrated activity in patients with relapsed/refractory MCL, the role of this drug in clinical practice is not clear given the increased use of BTK inhibitors as a preferred second-line therapy and ongoing concerns regarding PI3K inhibitor-related toxicity.

Additional References

1.      Wang Y, Jain P, Locke FL, et al. Brexucabtagene autoleucel for relapsed or refractory mantle cell lymphoma in standard-of-care practice: Results from the US Lymphoma CAR T Consortium. J Clin Oncol. 2023;41:2594-2606. doi: 10.1200/JCO.22.01797

2.      Rejeski K, Perez A, Sesques P, et al. CAR-HEMATOTOX: A model for CAR T-cell-related hematologic toxicity in relapsed/refractory large B-cell lymphoma. Blood. 2021;138:2499-2513. doi: 10.1182/blood.2020010543

3.      Forero-Torres A, Ramchandren R, Yacoub A, et al. Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies. Blood. 2019;133:1742-1752. doi: 10.1182/blood-2018-08-867499

Key clinical point: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who respond to salvage chemotherapy immediately before chimeric antigen receptor (CAR) T-cell therapy administration have better survival outcomes than those with stable or progressive disease, irrespective of the administration timing.

Major finding: Patients who did vs did not respond to salvage chemotherapy immediately before receiving CAR T-cell therapy had significantly longer overall survival rates (P < .001). The number of prior lines of salvage chemotherapy or before CAR T-cell infusion was not significantly associated with overall survival (P = .28).

Study details: This single-center, retrospective study included 76 autologous stem cell transplantation-eligible patients with relapsed or refractory DLBCL who received second-line salvage chemotherapy with curative intent, of whom 30 patients achieved partial or complete response and 34 patients (with or without response) eventually received CAR T-cell therapy.

Disclosures: This study did not disclose the funding source. N Doki declared receiving lecture fees from various sources.

Source: Yagi Y et al. Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study. Cancer Med. 2023 (Aug 28). doi: 10.1002/cam4.6412

Key clinical point: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who respond to salvage chemotherapy immediately before chimeric antigen receptor (CAR) T-cell therapy administration have better survival outcomes than those with stable or progressive disease, irrespective of the administration timing.

Major finding: Patients who did vs did not respond to salvage chemotherapy immediately before receiving CAR T-cell therapy had significantly longer overall survival rates (P < .001). The number of prior lines of salvage chemotherapy or before CAR T-cell infusion was not significantly associated with overall survival (P = .28).

Study details: This single-center, retrospective study included 76 autologous stem cell transplantation-eligible patients with relapsed or refractory DLBCL who received second-line salvage chemotherapy with curative intent, of whom 30 patients achieved partial or complete response and 34 patients (with or without response) eventually received CAR T-cell therapy.

Disclosures: This study did not disclose the funding source. N Doki declared receiving lecture fees from various sources.

Source: Yagi Y et al. Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study. Cancer Med. 2023 (Aug 28). doi: 10.1002/cam4.6412

Key clinical point: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who respond to salvage chemotherapy immediately before chimeric antigen receptor (CAR) T-cell therapy administration have better survival outcomes than those with stable or progressive disease, irrespective of the administration timing.

Major finding: Patients who did vs did not respond to salvage chemotherapy immediately before receiving CAR T-cell therapy had significantly longer overall survival rates (P < .001). The number of prior lines of salvage chemotherapy or before CAR T-cell infusion was not significantly associated with overall survival (P = .28).

Study details: This single-center, retrospective study included 76 autologous stem cell transplantation-eligible patients with relapsed or refractory DLBCL who received second-line salvage chemotherapy with curative intent, of whom 30 patients achieved partial or complete response and 34 patients (with or without response) eventually received CAR T-cell therapy.

Disclosures: This study did not disclose the funding source. N Doki declared receiving lecture fees from various sources.

Source: Yagi Y et al. Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study. Cancer Med. 2023 (Aug 28). doi: 10.1002/cam4.6412

Key clinical point: Radiation therapy (RT) as a bridging or salvage approach leads to favorable in‐field control and minimal toxicity in patients with relapsed or refractory mantle cell lymphoma (MCL) undergoing CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy.

Major finding: At a median RT dose of 15 Gy, the in-field complete response and partial response rates were 86% and 14%, respectively, with a 100% local control rate. Low-dose RT (3.6-6 Gy) achieved similar rates of in-field complete response (70%) and partial response (30%), with the local control rate remaining unchanged. Only one patient experienced grade 3 RT dermatitis after undergoing 40 Gy RT in 16 fractions.

Study details: This retrospective study included 21 patients with relapsed or refractory MCL who were treated with CD19‐targeted CAR T‐cell therapy, of whom 7 patients received prior bridging RT, post‐CAR T salvage RT, or both at 23 sites.

Disclosures: This study did not report any funding source. MJ Frigault declared serving as a consultant for and receiving research funding from various organizations.

Source: Ababneh HS et al. Radiation therapy for patients with relapsed or refractory mantle cell lymphoma undergoing CD19-targeted chimeric antigen receptor T-cell therapy. Hematol Oncol. 2023 (Sep 7). doi: 10.1002/hon.3221

Key clinical point: Radiation therapy (RT) as a bridging or salvage approach leads to favorable in‐field control and minimal toxicity in patients with relapsed or refractory mantle cell lymphoma (MCL) undergoing CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy.

Major finding: At a median RT dose of 15 Gy, the in-field complete response and partial response rates were 86% and 14%, respectively, with a 100% local control rate. Low-dose RT (3.6-6 Gy) achieved similar rates of in-field complete response (70%) and partial response (30%), with the local control rate remaining unchanged. Only one patient experienced grade 3 RT dermatitis after undergoing 40 Gy RT in 16 fractions.

Study details: This retrospective study included 21 patients with relapsed or refractory MCL who were treated with CD19‐targeted CAR T‐cell therapy, of whom 7 patients received prior bridging RT, post‐CAR T salvage RT, or both at 23 sites.

Disclosures: This study did not report any funding source. MJ Frigault declared serving as a consultant for and receiving research funding from various organizations.

Source: Ababneh HS et al. Radiation therapy for patients with relapsed or refractory mantle cell lymphoma undergoing CD19-targeted chimeric antigen receptor T-cell therapy. Hematol Oncol. 2023 (Sep 7). doi: 10.1002/hon.3221

Key clinical point: Radiation therapy (RT) as a bridging or salvage approach leads to favorable in‐field control and minimal toxicity in patients with relapsed or refractory mantle cell lymphoma (MCL) undergoing CD19‐targeted chimeric antigen receptor (CAR) T‐cell therapy.

Major finding: At a median RT dose of 15 Gy, the in-field complete response and partial response rates were 86% and 14%, respectively, with a 100% local control rate. Low-dose RT (3.6-6 Gy) achieved similar rates of in-field complete response (70%) and partial response (30%), with the local control rate remaining unchanged. Only one patient experienced grade 3 RT dermatitis after undergoing 40 Gy RT in 16 fractions.

Study details: This retrospective study included 21 patients with relapsed or refractory MCL who were treated with CD19‐targeted CAR T‐cell therapy, of whom 7 patients received prior bridging RT, post‐CAR T salvage RT, or both at 23 sites.

Disclosures: This study did not report any funding source. MJ Frigault declared serving as a consultant for and receiving research funding from various organizations.

Source: Ababneh HS et al. Radiation therapy for patients with relapsed or refractory mantle cell lymphoma undergoing CD19-targeted chimeric antigen receptor T-cell therapy. Hematol Oncol. 2023 (Sep 7). doi: 10.1002/hon.3221

Key clinical point: In low endemic areas for hepatitis B surface antigen, patients with past or active hepatitis B virus (HBV) infections have an increased risk for diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with DLBCL, but not with various types of indolent B-cell non-Hodgkin lymphomas (NHL), had a significantly higher prevalence of chronic (P = .008) and past (P = 0.002) HBV infections vs HBV-negative serology. The DLBCL vs pooled indolent B-cell NHL group had a significantly higher prevalence of chronic (adjusted odds ratio [aOR] 2.8; P = .014) and past (aOR 2.4; P = .0006) HBV infections.

Study details: This retrospective single-center study included patients with DLBCL (n = 253) or different types of indolent B-cell NHL (n = 694) who had either chronic or past HBV infections or no serological evidence for either.

Disclosures: This study was supported by grants from the Intramural Research Program of Sapienza University of Rome. The authors declared no conflicts of interest.

Source: Visentini M et al. High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: A retrospective study from Italy. Ann Hematol. 2023 (Aug 31). doi: 10.1007/s00277-023-05412-1

Key clinical point: In low endemic areas for hepatitis B surface antigen, patients with past or active hepatitis B virus (HBV) infections have an increased risk for diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with DLBCL, but not with various types of indolent B-cell non-Hodgkin lymphomas (NHL), had a significantly higher prevalence of chronic (P = .008) and past (P = 0.002) HBV infections vs HBV-negative serology. The DLBCL vs pooled indolent B-cell NHL group had a significantly higher prevalence of chronic (adjusted odds ratio [aOR] 2.8; P = .014) and past (aOR 2.4; P = .0006) HBV infections.

Study details: This retrospective single-center study included patients with DLBCL (n = 253) or different types of indolent B-cell NHL (n = 694) who had either chronic or past HBV infections or no serological evidence for either.

Disclosures: This study was supported by grants from the Intramural Research Program of Sapienza University of Rome. The authors declared no conflicts of interest.

Source: Visentini M et al. High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: A retrospective study from Italy. Ann Hematol. 2023 (Aug 31). doi: 10.1007/s00277-023-05412-1

Key clinical point: In low endemic areas for hepatitis B surface antigen, patients with past or active hepatitis B virus (HBV) infections have an increased risk for diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with DLBCL, but not with various types of indolent B-cell non-Hodgkin lymphomas (NHL), had a significantly higher prevalence of chronic (P = .008) and past (P = 0.002) HBV infections vs HBV-negative serology. The DLBCL vs pooled indolent B-cell NHL group had a significantly higher prevalence of chronic (adjusted odds ratio [aOR] 2.8; P = .014) and past (aOR 2.4; P = .0006) HBV infections.

Study details: This retrospective single-center study included patients with DLBCL (n = 253) or different types of indolent B-cell NHL (n = 694) who had either chronic or past HBV infections or no serological evidence for either.

Disclosures: This study was supported by grants from the Intramural Research Program of Sapienza University of Rome. The authors declared no conflicts of interest.

Source: Visentini M et al. High prevalence of past hepatitis B virus infection in diffuse large B cell lymphoma: A retrospective study from Italy. Ann Hematol. 2023 (Aug 31). doi: 10.1007/s00277-023-05412-1

Key clinical point: Bendamustine lymphodepletion (LD) relative to fludarabine/cyclophosphamide (Flu/Cy) LD prior to axicabtagene ciloleucel (axi-cel) therapy leads to comparable efficacy and lower rates of any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with relapsed or refractory aggressive B-cell lymphoma (aBCL).

Major finding: The bendamustine and Flu/Cy cohorts had similar rates of best overall response (77.8%, 95% CI 57.7%-91.4%; and 81.0%, 95% CI 65.9%-91.4%, respectively) and complete response (48.1%, 95% CI 28.7%-68.1%; and 50.0%, 95% CI 34.2%-65.8%, respectively), 6-month progression-free survival (43.8%, 95% CI 24.7%-61.3%; and 55.6%, 95% CI 39.0%-69.3%, respectively), and 6-month overall survival (81.5%, 95% CI 61.1%-91.8%; and 90.4%, 95% CI 76.4%-96.3%, respectively). Bendamustine vs Flu/Cy was associated with decreased odds of any-grade ICANS (odds ratio 0.35; 95% CI 0.12-0.97).

Study details: This retrospective study included patients with relapsed or refractory aBCL who received bendamustine (n = 27) or Flu/Cy (n = 42) LD before axi-cel therapy.

Disclosures: This study did not receive any funding. Some authors declared serving as speaker's bureau members or consultants for or receiving research funding or honoraria from various organizations.

Source: Ong SY et al. Bendamustine lymphodepletion is a well-tolerated alternative to fludarabine and cyclophosphamide lymphodepletion for axicabtagene ciloleucel therapy for aggressive B-cell lymphoma. Am J Hematol. 2023 (Sep 5). doi: 10.1002/ajh.27069

Key clinical point: Bendamustine lymphodepletion (LD) relative to fludarabine/cyclophosphamide (Flu/Cy) LD prior to axicabtagene ciloleucel (axi-cel) therapy leads to comparable efficacy and lower rates of any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with relapsed or refractory aggressive B-cell lymphoma (aBCL).

Major finding: The bendamustine and Flu/Cy cohorts had similar rates of best overall response (77.8%, 95% CI 57.7%-91.4%; and 81.0%, 95% CI 65.9%-91.4%, respectively) and complete response (48.1%, 95% CI 28.7%-68.1%; and 50.0%, 95% CI 34.2%-65.8%, respectively), 6-month progression-free survival (43.8%, 95% CI 24.7%-61.3%; and 55.6%, 95% CI 39.0%-69.3%, respectively), and 6-month overall survival (81.5%, 95% CI 61.1%-91.8%; and 90.4%, 95% CI 76.4%-96.3%, respectively). Bendamustine vs Flu/Cy was associated with decreased odds of any-grade ICANS (odds ratio 0.35; 95% CI 0.12-0.97).

Study details: This retrospective study included patients with relapsed or refractory aBCL who received bendamustine (n = 27) or Flu/Cy (n = 42) LD before axi-cel therapy.

Disclosures: This study did not receive any funding. Some authors declared serving as speaker's bureau members or consultants for or receiving research funding or honoraria from various organizations.

Source: Ong SY et al. Bendamustine lymphodepletion is a well-tolerated alternative to fludarabine and cyclophosphamide lymphodepletion for axicabtagene ciloleucel therapy for aggressive B-cell lymphoma. Am J Hematol. 2023 (Sep 5). doi: 10.1002/ajh.27069

Key clinical point: Bendamustine lymphodepletion (LD) relative to fludarabine/cyclophosphamide (Flu/Cy) LD prior to axicabtagene ciloleucel (axi-cel) therapy leads to comparable efficacy and lower rates of any-grade immune effector cell-associated neurotoxicity syndrome (ICANS) in patients with relapsed or refractory aggressive B-cell lymphoma (aBCL).

Major finding: The bendamustine and Flu/Cy cohorts had similar rates of best overall response (77.8%, 95% CI 57.7%-91.4%; and 81.0%, 95% CI 65.9%-91.4%, respectively) and complete response (48.1%, 95% CI 28.7%-68.1%; and 50.0%, 95% CI 34.2%-65.8%, respectively), 6-month progression-free survival (43.8%, 95% CI 24.7%-61.3%; and 55.6%, 95% CI 39.0%-69.3%, respectively), and 6-month overall survival (81.5%, 95% CI 61.1%-91.8%; and 90.4%, 95% CI 76.4%-96.3%, respectively). Bendamustine vs Flu/Cy was associated with decreased odds of any-grade ICANS (odds ratio 0.35; 95% CI 0.12-0.97).

Study details: This retrospective study included patients with relapsed or refractory aBCL who received bendamustine (n = 27) or Flu/Cy (n = 42) LD before axi-cel therapy.

Disclosures: This study did not receive any funding. Some authors declared serving as speaker's bureau members or consultants for or receiving research funding or honoraria from various organizations.

Source: Ong SY et al. Bendamustine lymphodepletion is a well-tolerated alternative to fludarabine and cyclophosphamide lymphodepletion for axicabtagene ciloleucel therapy for aggressive B-cell lymphoma. Am J Hematol. 2023 (Sep 5). doi: 10.1002/ajh.27069

Key clinical point: Concurrent MYC overexpression and TP53/p53 alterations in tumors identifies a subset of patients with mantle cell lymphoma (MCL) having a poor prognosis with a median overall survival < 3 years.

Major finding: Patients with tumors comprising > 20% cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04). Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of 0.9 years only (both P < .001).

Study details: The data come from a study including 252 patients with MCL, 14% of whom had MYC^high tumors, including 13 patients with concomitant MYC^high expression and TP53/p53 alterations.

Disclosures: This study was funded by the European Union’s Horizon 2020 Research and Innovation Programme. Some authors declared receiving research support or honoraria from or participating in educational sessions or advisory boards of various organizations.

Source: Rodrigues JM et al. MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 - A Nordic Lymphoma Group study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283352

Key clinical point: Concurrent MYC overexpression and TP53/p53 alterations in tumors identifies a subset of patients with mantle cell lymphoma (MCL) having a poor prognosis with a median overall survival < 3 years.

Major finding: Patients with tumors comprising > 20% cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04). Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of 0.9 years only (both P < .001).

Study details: The data come from a study including 252 patients with MCL, 14% of whom had MYC^high tumors, including 13 patients with concomitant MYC^high expression and TP53/p53 alterations.

Disclosures: This study was funded by the European Union’s Horizon 2020 Research and Innovation Programme. Some authors declared receiving research support or honoraria from or participating in educational sessions or advisory boards of various organizations.

Source: Rodrigues JM et al. MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 - A Nordic Lymphoma Group study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283352

Key clinical point: Concurrent MYC overexpression and TP53/p53 alterations in tumors identifies a subset of patients with mantle cell lymphoma (MCL) having a poor prognosis with a median overall survival < 3 years.

Major finding: Patients with tumors comprising > 20% cells with MYC overexpression (MYC^high tumors) vs MYC^low tumors had significantly higher risks for death (adjusted hazard ratio [aHR] 2.03; P = .007) and disease progression (aHR 2.20; P = .04). Patients with tumors with concomitant MYC^high expression and TP53/p53 alterations vs MYC^low tumors had significantly increased risks for progression (HR 16.90) and death (HR 7.83) with a median overall survival of 0.9 years only (both P < .001).

Study details: The data come from a study including 252 patients with MCL, 14% of whom had MYC^high tumors, including 13 patients with concomitant MYC^high expression and TP53/p53 alterations.

Disclosures: This study was funded by the European Union’s Horizon 2020 Research and Innovation Programme. Some authors declared receiving research support or honoraria from or participating in educational sessions or advisory boards of various organizations.

Source: Rodrigues JM et al. MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 - A Nordic Lymphoma Group study. Haematologica. 2023 (Aug 31). doi: 10.3324/haematol.2023.283352

Key clinical point: Parsaclisib provided rapid and durable responses and a manageable safety profile in patients with relapsed or refractory follicular lymphoma (FL).

Major finding: Among patients receiving parsaclisib daily, 77.7% (95% CI 68.4%-85.3%) achieved an objective response and 19.4% (95% CI 12.3%-28.4%) achieved a complete response. The median duration of response was 14.7 months (95% CI 10.4-not estimable) and the median time to response was 8.1 weeks. Most treatment-emergent adverse events were low-grade and manageable by dose interruptions or reductions.

Study details: This phase 2 CITADEL-203 study included 126 adult Bruton tyrosine kinase inhibitor-naive patients with relapsed or refractory FL previously treated with ≥2 systemic therapies who received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly (n = 23) or 2.5 mg parsaclisib once daily (n = 103).

Disclosures: This study was sponsored by Incyte Corporation, USA. Some authors declared serving as consultants or speakers for or receiving honoraria, research funding, or reimbursements for travel, accommodations, or expenses from Incyte and other sources. Four authors declared being employees and stockowners of Incyte.

Source: Trněný M et al. Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory follicular lymphoma (CITADEL-203): A phase 2 study. EClinicalMedicine. 2023;63:102130 (Aug 18). doi: 10.1016/j.eclinm.2023.102130

Key clinical point: Parsaclisib provided rapid and durable responses and a manageable safety profile in patients with relapsed or refractory follicular lymphoma (FL).

Major finding: Among patients receiving parsaclisib daily, 77.7% (95% CI 68.4%-85.3%) achieved an objective response and 19.4% (95% CI 12.3%-28.4%) achieved a complete response. The median duration of response was 14.7 months (95% CI 10.4-not estimable) and the median time to response was 8.1 weeks. Most treatment-emergent adverse events were low-grade and manageable by dose interruptions or reductions.

Study details: This phase 2 CITADEL-203 study included 126 adult Bruton tyrosine kinase inhibitor-naive patients with relapsed or refractory FL previously treated with ≥2 systemic therapies who received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly (n = 23) or 2.5 mg parsaclisib once daily (n = 103).

Disclosures: This study was sponsored by Incyte Corporation, USA. Some authors declared serving as consultants or speakers for or receiving honoraria, research funding, or reimbursements for travel, accommodations, or expenses from Incyte and other sources. Four authors declared being employees and stockowners of Incyte.

Source: Trněný M et al. Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory follicular lymphoma (CITADEL-203): A phase 2 study. EClinicalMedicine. 2023;63:102130 (Aug 18). doi: 10.1016/j.eclinm.2023.102130

Key clinical point: Parsaclisib provided rapid and durable responses and a manageable safety profile in patients with relapsed or refractory follicular lymphoma (FL).

Major finding: Among patients receiving parsaclisib daily, 77.7% (95% CI 68.4%-85.3%) achieved an objective response and 19.4% (95% CI 12.3%-28.4%) achieved a complete response. The median duration of response was 14.7 months (95% CI 10.4-not estimable) and the median time to response was 8.1 weeks. Most treatment-emergent adverse events were low-grade and manageable by dose interruptions or reductions.

Study details: This phase 2 CITADEL-203 study included 126 adult Bruton tyrosine kinase inhibitor-naive patients with relapsed or refractory FL previously treated with ≥2 systemic therapies who received 20 mg parsaclisib once daily for 8 weeks followed by either 20 mg parsaclisib once weekly (n = 23) or 2.5 mg parsaclisib once daily (n = 103).

Disclosures: This study was sponsored by Incyte Corporation, USA. Some authors declared serving as consultants or speakers for or receiving honoraria, research funding, or reimbursements for travel, accommodations, or expenses from Incyte and other sources. Four authors declared being employees and stockowners of Incyte.

Source: Trněný M et al. Parsaclisib, a PI3Kδ inhibitor, in relapsed and refractory follicular lymphoma (CITADEL-203): A phase 2 study. EClinicalMedicine. 2023;63:102130 (Aug 18). doi: 10.1016/j.eclinm.2023.102130

Key clinical point: Compared with the conventional third line or higher lines of chemotherapy, tisagenlecleucel led to a 41% reduction in the risk for death in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients receiving tisagenlecleucel vs conventional treatments had significantly longer median overall survival (11.7 vs 5.4 months; adjusted hazard ratio 0.59; P = .0035).

Study details: This study analyzed the published summary data of patients with relapsed or refractory DLBCL treated with tisagenlecleucel in the JULIET study (n = 111) and the real-world individual patient data of those treated with conventional therapies in the first and second Samsung Medical Center-Lymphoma Cohort studies (n = 53).

Disclosures: This study was supported by grants from the Ministry of Food and Drug Safety, South Korea. S Park and JY Shin declared receiving grants from various sources.

Source: Park S et al. Comparison of tisagenlecleucel with conventional treatments for relapsed/refractory diffuse large B-cell lymphomas: A retrospective external comparator study. Blood Cancer J. 2023;13:123 (Aug 18). doi: 10.1038/s41408-023-00889-5

Key clinical point: Compared with the conventional third line or higher lines of chemotherapy, tisagenlecleucel led to a 41% reduction in the risk for death in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients receiving tisagenlecleucel vs conventional treatments had significantly longer median overall survival (11.7 vs 5.4 months; adjusted hazard ratio 0.59; P = .0035).

Study details: This study analyzed the published summary data of patients with relapsed or refractory DLBCL treated with tisagenlecleucel in the JULIET study (n = 111) and the real-world individual patient data of those treated with conventional therapies in the first and second Samsung Medical Center-Lymphoma Cohort studies (n = 53).

Disclosures: This study was supported by grants from the Ministry of Food and Drug Safety, South Korea. S Park and JY Shin declared receiving grants from various sources.

Source: Park S et al. Comparison of tisagenlecleucel with conventional treatments for relapsed/refractory diffuse large B-cell lymphomas: A retrospective external comparator study. Blood Cancer J. 2023;13:123 (Aug 18). doi: 10.1038/s41408-023-00889-5

Key clinical point: Compared with the conventional third line or higher lines of chemotherapy, tisagenlecleucel led to a 41% reduction in the risk for death in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients receiving tisagenlecleucel vs conventional treatments had significantly longer median overall survival (11.7 vs 5.4 months; adjusted hazard ratio 0.59; P = .0035).

Study details: This study analyzed the published summary data of patients with relapsed or refractory DLBCL treated with tisagenlecleucel in the JULIET study (n = 111) and the real-world individual patient data of those treated with conventional therapies in the first and second Samsung Medical Center-Lymphoma Cohort studies (n = 53).

Disclosures: This study was supported by grants from the Ministry of Food and Drug Safety, South Korea. S Park and JY Shin declared receiving grants from various sources.

Source: Park S et al. Comparison of tisagenlecleucel with conventional treatments for relapsed/refractory diffuse large B-cell lymphomas: A retrospective external comparator study. Blood Cancer J. 2023;13:123 (Aug 18). doi: 10.1038/s41408-023-00889-5

Key clinical point: The baseline CAR-HEMATOTOX (HT) score enables the early identification of patients at high risk for prolonged neutropenia, severe infections, and poor survival outcomes following brexucabtagene autoleucel (brexu-cel) infusion for relapsed or refractory mantle cell lymphoma (MCL).

Major finding: Patients with high (score 2-7) vs low (score 0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (adjusted hazard ratio [aHR] 3.7; P < .001) and overall (aHR 5.6; P = .002) survival.

Study details: This multicenter observational study included 103 patients with relapsed or refractory MCL receiving brexu-cel, of whom 47 patients had high and 56 patients had low HT scores.

Disclosures: This study was supported by the Gilead Research Scholar Program and other sources. Some authors declared serving as consultants or advisory board members for or receiving research funding, speakers’ honoraria, personal fees, or travel support from Gilead Sciences and other sources.

Source: Rejeski K et al. The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. Am J Hematol. 2023 (Aug 16). doi: 10.1002/ajh.27056

Key clinical point: The baseline CAR-HEMATOTOX (HT) score enables the early identification of patients at high risk for prolonged neutropenia, severe infections, and poor survival outcomes following brexucabtagene autoleucel (brexu-cel) infusion for relapsed or refractory mantle cell lymphoma (MCL).

Major finding: Patients with high (score 2-7) vs low (score 0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (adjusted hazard ratio [aHR] 3.7; P < .001) and overall (aHR 5.6; P = .002) survival.

Study details: This multicenter observational study included 103 patients with relapsed or refractory MCL receiving brexu-cel, of whom 47 patients had high and 56 patients had low HT scores.

Disclosures: This study was supported by the Gilead Research Scholar Program and other sources. Some authors declared serving as consultants or advisory board members for or receiving research funding, speakers’ honoraria, personal fees, or travel support from Gilead Sciences and other sources.

Source: Rejeski K et al. The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. Am J Hematol. 2023 (Aug 16). doi: 10.1002/ajh.27056

Key clinical point: The baseline CAR-HEMATOTOX (HT) score enables the early identification of patients at high risk for prolonged neutropenia, severe infections, and poor survival outcomes following brexucabtagene autoleucel (brexu-cel) infusion for relapsed or refractory mantle cell lymphoma (MCL).

Major finding: Patients with high (score 2-7) vs low (score 0-1) HT scores had significantly longer median duration of severe neutropenia (P < .0001), higher rates of severe infections (P = .001), and lower overall response rates (P = .003). The HT score represented an independent predictor of poor progression-free (adjusted hazard ratio [aHR] 3.7; P < .001) and overall (aHR 5.6; P = .002) survival.

Study details: This multicenter observational study included 103 patients with relapsed or refractory MCL receiving brexu-cel, of whom 47 patients had high and 56 patients had low HT scores.

Disclosures: This study was supported by the Gilead Research Scholar Program and other sources. Some authors declared serving as consultants or advisory board members for or receiving research funding, speakers’ honoraria, personal fees, or travel support from Gilead Sciences and other sources.

Source: Rejeski K et al. The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL. Am J Hematol. 2023 (Aug 16). doi: 10.1002/ajh.27056