Ide-cel superior to standard therapies in triple-class exposed RRMM

Idecabtagene vicleucel (ide-cel) outperformed standard regimens in patients with triple-class exposed relapsed and refractory multiple myeloma (RRMM). The results of the phase 3 KarMMa-3 study supported the use of ide-cel in this hard-to-treat population.

“Novel therapies are needed in earlier lines of treatment for patients with MM,” stated Dr Paula Rodríguez-Otero (Clinica Universidad de Navarra, Spain) [1,2]. “The B-cell maturation antigen [BCMA]-directed CAR T-cell therapy ide-cel has displayed promising efficacy in a heavily pre-treated population of patients with RRMM, and we aimed to study this agent in earlier lines of therapy” [1,3]. The phase 3 KarMMa-3 trial (NCT03651128) compared ide-cel with standard treatment regimens in patients with triple-class exposed RRMM who had received 2 to 4 prior lines of therapy and were refractory to the last treatment regimen (n=386). The participants were randomised 2:1 to ide-cel or standard treatment. Progression-free survival (PFS) was the primary endpoint.

The median PFS was significantly longer in patients who received ide-cel compared with those who received a standard regimen (13.3 months vs 4.4 months; HR 0.49; 95% CI 0.38–0.65; P<0.0001; see Figure). “This result was consistent across subgroups, including older patients, those with a high tumour burden, and patients with high-risk cytogenetic abnormalities,” added Dr Rodríguez-Otero. Furthermore, the overall response rates (71% vs 42%; OR 3.47; P<0.0001) and the median duration of response (14.8 months vs 9.7 months) were higher in the ide-cel arm than in the control arm. Dr Rodriguez-Otero mentioned that the overall survival data were not yet mature at the time of the analysis. Finally, the safety data were consistent with the ide-cel toxicity profile reported in previous studies [1,4].

Figure: PFS in the intention-to-treat population of the KarMMa-3 study [1]



CI, confidence interval; HR, hazard ratio; ide-cel, idecabtagene vicleucel; PFS, progression-free survival.

In conclusion, the findings of the KarMMa-3 trial support the use of ide-cel in patients with early-line relapse and triple-class exposed RRMM, but OS data should be awaited.

1. Rodriguez-Otero P, et al. Idecabtagene vicleucel versus standard regimens in patients with triple-class-exposed relapsed and refractory multiple myeloma: KarMMa-3, a phase 3 randomized controlled trial. GS02-10, European Society for Blood and Marrow Transplantation (EBMT) 49^th Annual Meeting, 23–26 April 2023, Paris, France.
2. Rodríguez-Otero P, et al. N Engl J Med 2023;388:1002–1014.
3. Munshi NC, et al. N Engl J Med 2021;384:705–716.
4. Raje N, et al. N Engl J Med 2019;380:1726–1737.

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Posted on 15 June, 202318 March, 2024