Ciltacabtagene Autoleucel in Patients With Prior Allogeneic Stem Cell Transplant in the CARTITUDE-1 Study
Myo Htut, Binod Dhakal, Adam D. Cohen, Thomas Martin, Jesús G. Berdeja, Saad Z. Usmani, Mounzer Agha, Carolyn C. Jackson, Deepu Madduri, William Deraedt, Enrique Zudaire, Tzu‐Min Yeh, Xiaoying Xu, Lida Pacaud, Muhammad Akram, Sundar Jagannath
Abstract
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 5–7 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. Microabstract Treatment options for patients with relapsed/refractory multiple myeloma (RRMM) after relapse from allogeneic stem cell transplant (alloSCT) are needed. This study provides data around suitability of CAR-T therapy, specifically ciltacabtagene autoleucel, for heavily pretreated patients with RRMM and prior alloSCT. Patients in the CARTITUDE-1 study with prior alloSCT (n=7) had similar efficacy and safety profiles to those without prior alloSCT.