S202: CARTITUDE-1 FINAL RESULTS: PHASE 1B/2 STUDY OF CILTACABTAGENE AUTOLEUCEL IN HEAVILY PRETREATED PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
Nikhil C. Munshi, Tom Martin, Saad Z. Usmani, Jesús G. Berdeja, Andrzej Jakubowiak, Mounzer Agha, Adam D. Cohen, Abhinav Deol, Myo Htut, Alexander M. Lesokhin, Yi Lin, Elizabeth O’Donnell, Carolyn C. Jackson, Tzu‐Min Yeh, Arnob Banerjee, Enrique Zudaire, Deepu Madduri, Christopher delCorral, Lida Pacaud, Sundar Jagannath
Abstract
Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM) treated with standard of care therapy have median overall survival (OS) of ~12 months. In the single-arm, phase 1b/2 CARTITUDE-1 study (NCT03548207), patients received a single infusion of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor-T cell therapy targeting B-cell maturation antigen. At the final protocol-specified analysis (27.7-month median follow-up), overall response rate (ORR) was 98%, with 83% stringent complete response; 27-month rates of progression-free survival (PFS) and OS were 55% and 70%, respectively. Aims: To report CARTITUDE-1 study close out efficacy and safety results. Methods: Informed consent was obtained prior to study entry. Enrolled patients had received ≥3 prior lines of therapy (LOT) or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD); and had received prior PI, IMiD, and anti-CD38 antibody therapy. Primary endpoint was ORR and safety; secondary endpoints included PFS, OS, and minimal residual disease (MRD)-negativity at 10-5. Results: 97 patients received cilta-cel (59% male; median age 61 years; median of 6 prior LOT; 42% penta-drug refractory; 88% triple-class refractory; 99% refractory to last LOT). As of October 14, 2022, median follow-up was 33.4 months (range, 1.5−45.2). Median duration of response was 33.9 month (95% CI, 25.5–not estimable [NE]). Median PFS was 34.9 months (95% CI, 25.2–NE), with an estimated 47.5% of patients progression free and alive at 36 months. Median OS was not reached, with an estimated 62.9% survival at 36 months. Of 49 MRD-evaluable patients, 26 had MRD-negativity sustained for ≥12 months, of which 20 had sustained MRD-negative complete response (CR) or better. Median PFS was not reached in these subgroups (Table). Eighteen patients were MRD-negative with ≥CR at 24-months post infusion. No new safety signals and no new neurotoxicity events were reported since the 27.7-month median follow-up. Six new cases of second primary malignancy were reported, including 2 cases of basal cell carcinoma and 1 case each of myelodysplastic syndrome, B-cell lymphoma, melanoma, and prostate cancer. Five additional deaths occurred (progressive disease [PD], n=3; pneumonia and sepsis, n=1 each [both unrelated to cilta-cel]), for a total of 35 deaths (PD, n=17; unrelated to cilta-cel, n=12; related, n=6). Summary/Conclusion: Longer median PFS was observed after a single infusion of cilta-cel than any previously reported therapy in heavily pretreated patients with RRMM. Achieving CR and/or sustained MRD-negativity was associated with prolonged PFS. Patients continue to be followed for safety and survival in the 15-year CARTINUE long-term study (NCT05201781; MMY4002). © 2023 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2023 ASCO Annual Meeting. All rights reserved.Keywords: Phase I/II, Clinical trial, CAR-T, Multiple myeloma