Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study.

BACKGROUND

Patients with prior allogeneic stem cell transplant (alloSCT) are typically excluded from trials of chimeric antigen receptor (CAR) T cell therapies, because their engineered cells may include allogeneic T cells. Ciltacabtagene autoleucel (cilta-cel) demonstrated early, deep, durable responses and manageable safety in heavily pretreated relapsed/refractory multiple myeloma patients. We retrospectively analyzed patients who received alloSCT prior to cilta-cel in CARTITUDE-1.

PATIENTS AND METHODS

Patients eligible for CARTITUDE-1 were ≥18 years, had ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD) and had received a PI, IMiD, and anti-CD38 antibody. Patients with active graft-versus-host disease (GVHD) or had alloSCT within 6 months before apheresis were excluded. Patients received cilta-cel 5 to 7 days after lymphodepletion.

RESULTS

Patients (N = 7) received median 9 prior LOTs (range, 6-14); median time since alloSCT was 5.1 years (range, 2.7-6.2). At median follow-up 27.7 months after cilta-cel infusion, overall response rate was 85.7% (n = 6). The safety profile was generally consistent with patients without alloSCT as prior therapy (cytokine release syndrome, 85.7% vs. 95.6%, respectively; immune effector cell-associated neurotoxicity syndrome, 14.3% vs. 16.7%). One patient with prior alloSCT had grade 3 movement and neurocognitive treatment-emergent adverse events/parkinsonism. No GVHD cases were reported. Two patients died due to adverse events (treatment-related lung abscess; unrelated liver failure).

CONCLUSION

Cilta-cel efficacy and safety were comparable between CARTITUDE-1 patients with and without prior alloSCT. Additional studies are needed to fully elucidate the suitability of CAR-T cell therapy in the post-alloSCT setting.

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Disclosure M. Htut consulted and served on advisory committees for and received travel funding from Millennium; and received research funding from Judy and Bernard Briskin Center for Multiple Myeloma Research (Inst) and BMS (Inst). B. Dhakal consulted and served on advisory committees for Amgen, Takeda, Janssen, GlaxoSmithKline, Natera, and Sanofi; received honoraria from Celgene, Karyopharm Therapeutics, Sanofi, and GlaxoSmithKline; and received research funding from Amgen, Janssen, and GlaxoSmithKline. A.D. Cohen consulted and served on advisory committees for Celgene, Janssen Oncology, Oncopeptides, Takeda, Seattle Genetics, GlaxoSmithKline, Novartis, Bristol-Myers Squibb, AstraZeneca, and Roche/Genentech; received research funding from Novartis (Inst) and GlaxoSmithKline (Inst); has patents related to CAR-T cells and biomarkers of cytokine release syndrome; has given expert testimony for Janssen Oncology; and received travel funding from GlaxoSmithKline, Takeda, Celgene, and Janssen Oncology. T. Martin consulted and served on advisory committees for GlaxoSmithKline and Legend Biotech USA Inc. and received research funding from Sanofi (Inst), Amgen (Inst), and Janssen Oncology (Inst). J.G. Berdeja consulted and served on advisory committees for Takeda (Inst), Bristol-Myers Squibb (Inst), CRISPR Therapeutics (Inst), Celgene (Inst), Kite, a Gilead company (Inst), Janssen (Inst), Legend Biotech (Inst), Secura Bio (Inst), and Bluebird Bio (Inst); and received research funding from Celgene (Inst), Takeda (Inst), Bristol-Myers Squibb (Inst), Amgen (Inst), Janssen (Inst), Novartis (Inst), AbbVie (Inst), Bluebird Bio (Inst), Teva (Inst), Genentech/Roche (Inst), Poseida Therapeutics (Inst), Sanofi (Inst), Acetylon Pharmaceuticals (Inst), Lilly (Inst), Celularity (Inst), CRISPR Therapeutics (Inst), EMD Serono (Inst), Ichnos Sciences (Inst), GlaxoSmithKline (Inst), and Incyte (Inst). S.Z. Usmani consulted and served on advisory committees for Celgene, Amgen, Janssen Oncology, Seattle Genetics, Takeda, GlaxoSmithKline, Karyopharm Therapeutics, AbbVie, SkylineDx, Merck, Oncopeptides, Genentech, Gilead Sciences, and Bristol-Myers Squibb/Celgene; served on speakers’ bureaus for Takeda, Amgen, Janssen Oncology, Sanofi, and Bristol-Myers Squibb/Celgene; and received research funding from Celgene, Array BioPharma, Janssen Oncology, Pharmacyclics, Sanofi, Bristol-Myers Squibb, Amgen, Seattle Genetics, Merck, SkylineDx, and GlaxoSmithKline. M. Agha owns stock in GenCART, Inc. D. Madduri is employed by Janssen Oncology; owns stock in Roivant; and consulted and served on advisory committees for Takeda, Janssen Oncology, Celgene, Legend Biotech USA Inc., GlaxoSmithKline, and Foundation Medicine. C.C. Jackson is employed by Janssen and owns stock in Janssen; and served as a consultant physician for Memorial Sloan Kettering Cancer Center. W. Deraedt, T.-m. Yeh, and X. Xu are employed by and own stock in Janssen. E. Zudaire is employed by, owns stock in, received travel funding from, and has patents pending with Janssen. L. Pacaud is employed by and owns stock in Legend Biotech USA Inc. M. Akram is employed by Legend Biotech USA, Inc. S. Jagannath consulted and served on advisory committees for Bristol-Myers Squibb, Janssen, Karyopharm Therapeutics, Legend Biotech USA Inc., Takeda, and Sanofi; and received travel funding from Bristol-Myers Squibb and Janssen.