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. 2023 Nov 30;7(12):e984.
doi: 10.1097/HS9.0000000000000984. eCollection 2023 Dec.

CAR-T Cell Therapy Shows Similar Efficacy and Toxicity in Patients With DLBCL Regardless of CNS Involvement

Evgenii Shumilov  1 , Hristo Boyadzhiev  2 , Paolo Mazzeo  3 , Dilara Akhoundova  4 , Michael Daskalakis  5 , Urban Novak  4 , Georg Lenz  1 , Ulrike Bacher  5 , Thomas Pabst  4
Affiliations

CAR-T Cell Therapy Shows Similar Efficacy and Toxicity in Patients With DLBCL Regardless of CNS Involvement

Evgenii Shumilov et al. Hemasphere. .

Abstract

Efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) with central nervous system (CNS) involvement remain understudied. Here we analyzed the outcomes of CAR-T cell therapy in r/r DLBCL patients with CNS involvement and compared them with patients without CNS disease. Retrospective and monocentric comparative analysis of patient cohort with r/r DLBCL treated with CAR-T cell therapy: 15 patients with CNS versus 65 patients without CNS involvement. Overall response rates (80% versus 80%; P = 1.0), progression-free survival (P = 0.157), and overall survival (P = 0.393) were comparable for both cohorts. The frequency of cytokine release syndrome was comparable in the CNS and non-CNS cohorts; 93% versus 80%; P = 1.0. Numerically, immune effector-cell-associated neurotoxicity syndrome (all grades) was more frequent in patients with CNS manifestation (53% versus 29%; P = 0.063), although no grade 4 events were documented. Our study suggests that CAR-T cell therapy is effective and feasible in patients with r/r DLBCL and CNS manifestation.

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Conflict of interest statement

ES received honoraria from Amgen, BMS, Stemline, Sanofi, Incyte, Janssen, Takeda and JAZZ. GL received research grants not related to this article from AGIOS, AQUINOX, AstraZeneca, Bayer, Celgene, Gilead, Janssen, Morphosys, Novartis, Roche, and Verastem. GL received honoraria from ADC Therapeutics, Abbvie, Amgen, AstraZeneca, Bayer, BMS, Celgene, Constellation, Genase, Genmab, Gilead, Hexal-Sandoz, Immagene, Incyte, Janssen, Karyopharm, Lilly, Miltenyi, Morphosys, NanoString, Novartis, PentixaPharm, Roche, Sobi, and Takeda. All the other authors have no conflicts of interest to disclose.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Comparison of adverse events from CAR-T cell therapy in cohorts CNS vs non-CNS. (A) Comparison of CRS incidence. (B) Visualization of CRS grade distribution. (C) Comparison of ICANS incidence. (D) Visualization of ICANS grade distribution. CAR-T = chimeric antigen receptor T cells; CNS = central nervous system; CRS = cytokine release syndrome; ICANS = immune effector-cell–associated neurotoxicity syndrome.
Figure 2.
Figure 2.
Comparison of outcomes of CAR-T cell therapy in cohorts CNS vs non-CNS. (A) Comparison of ORRs and CR rates. (B) Distribution of best remission status. (C) OS. (D) Progression-free survival (PFS). CAR-T = chimeric antigen receptor T cells; CRR = complete response rate; CNS = central nervous system; ORR = overall response rate; OS = overall survival; PD = progressive disease; PR = partial remission; SD = stable disease.
Figure 3.
Figure 3.
Post-CAR-T outcomes and subsequent lymphoma therapies in patients with CNS manifestations preceding CAR-T cell therapy. CAR-T = chimeric antigen receptor T cells; CNS = central nervous system; CR = complete remission; MATRIX = methotrexate, cytarabine, thiotepa, rituximab; PD = progressive disease; PR = partial remission; SD = stable disease.
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