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.