Ciltacabtagene Autoleucel Maintains Deep and Durable Responses in MM With Longer Follow-up: CARTITUDE-1

Ciltacabtagene autoleucel (cilta-cel) yielded deep and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma (MM), which were maintained at a follow-up of 28 months, according to an updated analysis of the CARTITUDE-1 trial published in the Journal of Clinical Oncology.

CARTITUDE-1 is a single-arm, open-label, multicenter, phase Ib/II trial that enrolled patients with relapsed or refractory MM. Patients were required to have received ≥ 3 prior lines of therapy, including a proteosome inhibitor (PI), immunomodulatory drug (IMiD), and an anti-CD38 antibody, or to be double refractory to a PI and IMiD.

On the trial, patients received a single cilta-cel infusion 5 to 7 days after lymphodepletion. Retreatment with cilta-cel was permitted within the same dose range in patients with documented progressive disease ≥ 6 months after cilta-cel infusion with best response of at least minimal response who had no ongoing hematologic (grade ≥ 3) or nonhematologic (grade ≥ 2) toxicities.

The primary efficacy end point of the phase 2 portion of the trial was the overall response rate (ORR); secondary end points were rates of stringent complete response (sCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

At a median follow-up of 27.7 months (N = 97), the ORR was 97.9% (95% confidence interval [CI], 92.7 to 99.7) and 82.5% (95% CI, 73.4 to 89.4) of patients achieved a sCR. Median DOR was not estimable and median PFS and OS were not reached. The 27-month PFS and OS rates were 54.9% (95% CI, 44 to 64.6) and 70.4% (95% CI, 60.1 to 78.6), respectively.

Study authors noted that ORRs were high across all subgroups (95.1% to 100%). However, DOR, PFS and OS were shorter in patients with high-risk cytogenetics, International Staging System stage III, high tumor burden, or plasmacytomas. No new safety signals were reported.

In conclusion, “these longer-term data from CARTITUDE-1 in triple-class exposed patients with RRMM demonstrate deep and durable responses to cilta-cel over time, including in high-risk subgroups,” the study authors wrote, “The safety profile continues to be manageable. The recent approval of cilta-cel in the US and positive CHMP opinion by the EMA will help fill an unmet medical need in this difficult-to-treat population.”

“Patients from the CARTITUDE-1 trial will continue to be followed for up to 15 years after infusion in a separate study to further evaluate long-term efficacy and safety,” they added.

Source:

Martin T, Usmani SZ, Berdeja JG, et al. Ciltacabtagene Autoleucel, an Anti–B-cell Maturation Antigen Chimeric Antigen Receptor T-Cell Therapy, for Relapsed/Refractory Multiple Myeloma: CARTITUDE-1 2-Year Follow-Up. J Clinl Oncol. Published online June 4, 2022. doi:10.1200/jco.22.00842