Cilta-Cel Outperforms Conventional Therapies in R/R Multiple Myeloma

Luciano J. Costa, MD, PhD

Outcomes for patients with relapsed or refractory multiple myeloma who had previously received a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody improved with the use of ciltacabtagene autoleucel (cilta-cel) as compared with conventional therapies, according to findings from propensity score–matched analyses of the CARTITUDE-1 (NCT03548207) and MAMMOTH studies.

“Our analysis provides evidence of better outcomes with cilta-cel compared with conventional treatments in patients with relapsed/refractory multiple myeloma who had received a proteasome inhibitor, an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody using propensity score matching,” Luciano J. Costa, MD, PhD, of the O’Neal Comprehensive Cancer Center at the University of Alabama at Birmingham, explained in his presentation of the data at the 2021 European Hematologic Association (EHA) Congress.

After 1:1 propensity score matching, the study included 95 patients in the intent-to-treat population (ITT) and 69 patients in the modified ITT (mITT) population from both the CARTITUDE-1 and MAMMOTH trials.

In MAMMOTH, which served as the comparative control group for CARTITUDE-1, patients who received a non–CAR T-cell subsequent therapy after becoming refractory to a proteasome inhibitor, IMiD, and anti-CD38 monoclonal antibody while also not having renal failure or meeting the criteria for plasma cell leukemia were in the ITT population. The mITT population included patients who also did not experience death or progression within 47 days from study inclusion to therapy initiation.

The treatments for patients in MAMMOTH included pomalidomide (34% of patients), anti-CD38 monoclonal antibody (24%), carfilzomib (19%), and cytotoxic chemotherapy (35%) as next therapy.

For CARTITUDE-1, the ITT population was defined as patients who underwent apheresis, while the mITT population consisted of patients who also received a cilta-cel infusion.

The research team found that response and survival rates were significantly higher for patients in the CARTITUDE-1 study than patients in the MAMMOTH study. Focusing on the ITT populations, the overall response rate (ORR) was 84% for the CARTITUDE-1 population compared with 28% in the MAMMOTH population (odds ratio [OR], 13.4; 95% CI, 6.6-27.3; P < .001).

Survival data in the ITT populations were also significant for CAR T-cell therapy, with a 12-month progression-free survival (PFS) rate of 73% (95% CI, 64%-83%) for patients in the CARTITUDE-1 population and 12% (95% CI, 6%-21%) for patients in the MAMMOTH population. The 12-month overall survival (OS) rate followed suit, with rates of 83% (95% CI, 76%-91%) and 39% (95% CI, 30%-51%) in the CARTITUDE-1 and MAMMOTH populations, respectively.

The mITT analyses produced similar results to that of the ITT populations. The ORR for these patients was 96% in CARTITUDE-1 compared with 30% in MAMMOTH (OR, 50.3; 95% CI, 14.2-178.3; P < .001).

The 12-month PFS rate was 79% (95% CI, 69%-90%) in the CARTITUDE-1 population compared with 15% (95% CI, 7%-28%) in the MAMMOTH population (P < .001). More, the 12-month OS rates were 88% (95% CI, 81%-96%) and 35% (95% CI, 24%-51%), respectively (P < .001).

“In propensity score–matched analyses of ITT and mITT populations, ORR and 12-month PFS and OS rates were significantly higher in CARTITUDE-1 vs MAMMOTH,” wrote the investigators in their poster presentation of the data.

The CARTITUDE-1 trial treated patients with multiple myeloma who received 3 or more prior therapies or were double refractory to an IMiD and proteasome inhibitor, and who received a proteasome inhibitor, IMiD, and anti-CD38 monoclonal antibody. Eligible patients received a single cilta-cel infusion of 0.75 × 106 CAR-positive viable T cells/kg, which was given 5 to 7 days after starting lymphodepletion.

Eligible patients with multiple myeloma for the MAMMOTH study were previously treated for 4 or more weeks with an anti-CD38 monoclonal antibody regimen.

While the data are useful, the research team notes that study design differences between CARTITUDE-1 and MAMMOTH limit the results. Specifically, CARTITUDE-1 is a prospective clinical study, while MAMMOTH is retrospective and observational in design.

“In the absence of a direct comparator, however, this analysis indicates that cilta-cel outperforms currently available therapies for heavily pretreated patients with multiple myeloma,” concluded the investigators.

_Reference

_{Costa LJ, Lin Y, Martin T, et al. Comparison of Ciltacabtagene Autoleucel Versus Conventional Treatment inPatients With Relapsed/Refractory Multiple Myeloma. Presented at: 2021 European Hematologic Association Congress; Virtual. June 9-17, 2021. Abstract EP990.}