CARTITUDE-1: The Final Results

Ciltacabtagene Autoleucel's effects in heavily pretreated relapsed or refractory multiple myeloma

Dr. Nikhil Munshi discussed the results of a phase 1b/2 study of cilta-cel, a BCMA-targeting CAR-T therapy, in heavily pretreated patients with relapsed/refractory multiple myeloma. cilta-cel showed promising long-term efficacy, with a median progression-free survival (PFS) of 34.9 months and a median duration of response of 34 months. Approximately 63% of patients were alive at the three-year follow-up, and achieving complete response (CR) or sustained minimal residual disease (MRD) negativity was associated with prolonged PFS. The safety profile was manageable, with no new neurotoxicity events reported. The study confirmed the strong anti-myeloma activity of cilta-cel and demonstrated long-term benefits in this patient population.

• Cilta-cel is a BCMA-targeting CAR-T therapy used in relapsed/refractory multiple myeloma.
• In the first-in-human Legend 2 study, cilta-cel showed an overall survival of 56 months, compared to the standard of care of 9 to 12 months.
• The Phase 1b/2 CARTITUDE-1 study aimed to evaluate cilta-cel's outcomes with a longer median follow-up of 33.4 months.
• The primary endpoint of the study was safety, with overall response rate (ORR) as a secondary endpoint, along with PFS, overall survival, and MRD negativity.
• 97 patients were included in the study, with a median follow-up of 33.4 months.
• Patients had received a median of six lines of therapy and 25% had high-risk cytogenetics.
• The overall response rate was 98%, with 82.5% of patients achieving stringent CR.
• At the three-year follow-up, the median PFS was 34.9 months, and the duration of response was approximately 34 months.
• Approximately 62.9% of patients were alive at the three-year follow-up.
• Achieving CR or sustained MRD negativity was associated with prolonged PFS.
• There was no association between CAR-T persistence and clinical outcome.
• Safety profile was manageable, and no new neurotoxicity events were reported.
• Second primary malignancies were reported in 20 patients, including cutaneous, hematologic, and prostate cancer.
• A total of 35 deaths occurred during the study period, with five new deaths reported, all unrelated to cilta-cel.
• The results confirmed strong anti-myeloma activity and sustained long-term benefits in heavily pretreated patients.
• The study will continue to follow patients for safety in a 15-year CARTINUE continued long-term study.

Authors:
Nikhil Munshi, Tom Martin, Saad Z Usmani, Jesus Berdeja, Andrzej Jakubowiak, Mounzer Agha, Adam D Cohen, Abhinav Deol, Myo Htut, Alexander Lesokhin, Yi Lin, Elizabeth O’Donnell, Carolyn C Jackson, Tzu-Min Yeh, Arnob Banerjee, Enrique Zudaire, Deepu Madduri, Christopher delCorral, Lida Pacaud, Sundar Jagannath

Clinical Trial Information: NCT05201781; MMY4002