Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma
Sundar Jagannath, Thomas G. Martin, Yi Lin, Adam D. Cohen, Noopur Raje, Myo Htut, Abhinav Deol, Mounzer Agha, Jesús G. Berdeja, Alexander M. Lesokhin, Jessica J. Liegel, Adriana Rossi, Alex Lieberman-Cribbin, Saad Z. Usmani, Binod Dhakal, Samir Parekh, Huijun Li, Rui Wang, Rocío Montes de, Vicki Plaks, Huabin Sun, Arnob Banerjee, Jordan M. Schecter, Nikoletta Lendvai, Deepu Madduri, Tamar Lengil, Jieqing Zhu, Mythili Koneru, Muhammad Akram, Nitin Patel, Octavio Costa Filho, Andrzej Jakubowiak, Peter M. Voorhees
Abstract
CARTITUDE-1 evaluated ciltacabtagene autoleucel (cilta-cel) in patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). We describe overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety, with a median study follow-up of 61.3 months. For the 97 treated patients, median OS was 60.7 months (95% CI, 41.9 to not estimable). One third (32/97) of patients remain alive and progression-free for ≥5 years after a single cilta-cel infusion, without maintenance treatment. Twelve of these patients treated at a single center underwent serial minimal residual disease (MRD) and positron emission tomography-computed tomography assessments, and all (100%) were MRD-negative (at least 10 −5 threshold) and imaging-negative at year 5 or later after cilta-cel. Baseline characteristics, including the presence of high-risk cytogenetics and extramedullary disease, were generally comparable for the 32 patients who were progression-free for ≥5 years versus patients who had progressive disease by year 5. A trend of lower baseline tumor burden, higher fraction of naïve T-cells in the cilta-cel drug product, higher T cell-to-neutrophil ratio, higher hemoglobin and platelets at baseline, and higher effector-to-target ratio were associated with ≥5-year progression-free status. The safety profile of cilta-cel remained consistent with previous reports. To our knowledge, our data provide the first evidence that cilta-cel is potentially curative in patients with RRMM.