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. 2024 Oct 22;8(20):5290-5296.
doi: 10.1182/bloodadvances.2024013863.

CD19-directed CART therapy for T-cell/histiocyte-rich large B-cell lymphoma

Priyanka A Pophali  1 , Joshua A Fein  2 , Kwang W Ahn  3 , Molly Allbee-Johnson  4 , Nausheen Ahmed  5 , Farrukh T Awan  6 , Shatha Farhan  7 , Natalie S Grover  8 , Talal Hilal  9 , Madiha Iqbal  10 , Joseph Maakaron  11 , Dipenkumar Modi  12 , Elham Nasrollahi  13 , Levanto G Schachter  14 , Craig Sauter  15 , Mehdi Hamadani  4   16 , Alex Herrera  17 , Roni Shouval  18   19 , Mazyar Shadman  20
Affiliations

CD19-directed CART therapy for T-cell/histiocyte-rich large B-cell lymphoma

Priyanka A Pophali et al. Blood Adv. .

Abstract

T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the Center for International Blood and Marrow Transplant Research registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART therapy between 2018 and 2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range, 1-7) prior therapies and were treated with axicabtagene ciloleucel (69%). At median follow-up of 23 months after CART therapy, 2-year overall and progression-free survival were 42% (95% confidence interval [CI], 27-57) and 29% (95% CI, 17-43), respectively. In univariable analysis, poor performance status before CART therapy was associated with higher mortality (hazard ratio, 2.35; 95%CI, 1.02-5.5). The 2-year cumulative incidences of relapse/progression and nonrelapse mortality were 69% and 2%, respectively. Grade ≥3 cytokine release syndrome and immune effector cell-associated neurologic syndrome occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART therapy for R/R THRLBCL, ∼30% of patients were alive and progression free 2 years after CART therapy. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CARTs.

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Conflict of interest statement

Conflict-of-interest disclosure: M.H. reports research support/funding from Takeda Pharmaceutical, ADC Therapeutics, Spectrum Pharmaceuticals, and Astellas Pharma; reports consultancy with ADC Therapeutics, Omeros, CRISPR, Bristol Myers Squibb (BMS), Kite, AbbVie, Caribou, Genmab, and Autolus; serves on the speakers bureau of ADC Therapeutics, AstraZeneca, BeiGene, Kite. Data Monitoring Committee: Inc, Genentech, Myeloid Therapeutics, and CRISPR. C.S. has served as a paid consultant for Kite/a Gilead Company, Celgene/BMS, Gamida Cell, Karyopharm Therapeutics, Ono Pharmaceuticals, MorphoSys, CSL Behring, Syncopation Life Sciences, CRISPR Therapeutics, Ipsen Biopharmaceuticals Inc, and GlaxoSmithKline; and has received research funds for clinical trials from Juno Therapeutics, Celgene/BMS, BMS, Precision Biosciences, Actinium Pharmaceuticals, Sanofi-Genzyme, Cargo Therapeutics, and Nkarta. M.S. reports consulting for advisory boards, steering committees, or data safety monitoring committees of AbbVie, Genentech, AstraZeneca, Janssen, BeiGene, BMS, MorphoSys/Incyte, Kite Pharma, Eli Lilly, Mustang Bio, Fate therapeutics, Nurix, and Merck; received research funding from Mustang Bio, Genentech, AbbVie, BeiGene, AstraZeneca, Genmab, MorphoSys/Incyte, and Vincerx; holds stock options in Koi Biotherapeutics; and reports employment with BMS (spouse). J.M. reports grants or contracts from Gilead, Atara, CRISPR Therapeutics, Precision Biosciences, and Scripps Research Institute. T.H. reports consulting fees from BeiGene. P.A.P. reports consulting fees from Seagen. N.G. reports consulting fees from Kite, BMS, Seagen, ADC Therapeutics, and Caribou Biosciences; and reports participation on data safety monitoring board or advisory board for Novartis. L.S. reports serving on a data safety monitoring board for an investigator initiated trial (IIT) at Oregon Health & Science University Myeloma group without associated payments. F.T.A. reports consulting fees from Genentech, AstraZeneca, AbbVie, Janssen, Pharmacyclics, Gilead sciences, Kite pharma, Celgene, Karyopharm, MEI Pharma, Verastem, Incyte, BeiGene, Johnson and Johnson, Dava Oncology, BMS, Merck, Cardinal Health, ADC Therapeutics Therapeutics, Loxo Oncology, Adaptive Biotechnologies, Genmab, Epizyme, Caribou Biosciences, and Cellectar Biosciences; and has participated on a data safety monitoring board or advisory board for Ascentage Pharma and AstraZeneca. D.M. reports consulting fees from AstraZeneca (self and spouse); honoraria from BeiGene; and participation in data safety monitoring board or advisory board for Genmab, ADC Therapeutics, Seagen, and Genentech (spouse). N.A. reports consulting fees and travel support from Kite/Gilead; and honoraria from Nebraska Medical Oncology. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS and PFS of patients with relapsed THRLBCL treated with CD19-CART therapy in the CIBMTR registry.
Figure 2.
Figure 2.
Forrest plots of factors associated with survival outcomes. Univariable analysis of association with (A) OS and (B) PFS. allo-HCT, allogeneic hematopoietic cell transplantation; auto-HCT, autologous hematopoietic cell transplantation; KPS, Karnofsky performance status.
See this image and copyright information in PMC

Comment in

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