KEY TAKEAWAYS
- The phase 1b/2 CARTITUDE-1 study aimed to assess the efficacy and safety of cilta-cel infusion in heavily pretreated RRMM patients.
- The study’s primary endpoint was ORR and safety. Secondary endpoints were PFS, OS, and MRD-negativity at 10-5.
- The study showed that a single cilta-cel infusion resulted in a significantly extended median PFS compared to prior therapies in heavily treated RRMM patients.
The phase 1b/2 CARTITUDE-1 study enrolled heavily pretreated patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with standard-of-care therapy having median overall survival (OS) of ~12 months. Patients who had either undergone at least three previous lines of therapy (LOT) or were resistant to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) were included in this study. They had previously received treatment with a PI, IMiD, and anti-CD38 antibody.
The main objectives of the study were to assess the overall response rate (ORR) and safety. Secondary objectives included evaluating progression-free survival (PFS), overall survival (OS), and the absence of minimal residual disease (MRD) at a level of 10-5.
Ninety-seven pts were administered ciltacabtagene autoleucel (cilta-cel), with 59% male and a median age of 61. These pts had a median history of six prior LOT, 42% were refractory to a combination of five different drugs, 88% were refractory to three different drug classes, and 99% were refractory to the last treatment they received.
As of October 14, 2022, the median follow-up duration was 33.4 months, ranging from 1.5 to 45.2 months. The median duration of response was 33.9 months, with a confidence interval (CI) of 95% ranging from 25.5 to not estimable (NE). The median PFS was 34.9 months, with a CI of 95% ranging from 25.2 to NE. At 36 months, approximately 47.5% of pts were estimated to remain free from progression and alive. The median OS was not reached, but 62.9% of pts were expected to survive at 36 months. Of 49 pts evaluated for MRD, 26 maintained MRD-negativity for at least 12 months, with 20 achieving a sustained MRD-negative complete response (CR) or better.
In these subgroups, the median PFS had not been reached. Additionally, 18 pts remained MRD-negative with a complete response at 24 months post-infusion. No new safety concerns or neurotoxicity issues were reported beyond the 27.7-month median follow-up. Six new cases of second primary malignancies were reported, including two cases of basal cell carcinoma and one case each of myelodysplastic syndrome, B-cell lymphoma, melanoma, and prostate cancer. Furthermore, there were five additional deaths, three due to progressive disease (PD) and one each from pneumonia and sepsis (both unrelated to cilta-cel), bringing the total number of deaths to 35 (17 due to PD, 12 unrelated to cilta-cel, and 6 related to cilta-cel).
Longer median PFS was reported following a single cilta-cel infusion compared to any previously documented therapy in heavily treated RRMM pts. The attainment of CR and/or sustained MRD negativity was linked to a prolonged PFS. Ongoing patient monitoring for safety and long-term survival is being conducted in the 15-year CARTINUE long-term study (NCT05201781; MMY4002).
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03548207
Munshi, N., Martin, T., Usmani, S.Z., Berdeja, J., Jakubowiak, A., Agha, M., Cohen, A.D., Deol, A., Htut, M., Lesokhin, A., Lin, Y., O’Donnell, E., Jackson, C.C., Yeh, T-M., Banerjee, A., Zudaire, E., Madduri, D., delCorral, C., Pacaud, L., Jagannath, S. CARTITUDE-1 FINAL RESULTS: PHASE 1B/2 STUDY OF CILTACABTAGENE AUTOLEUCEL IN HEAVILY PRETREATED PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA. EHA Library. Munshi N. 06/08/2023; 387902; S202.
