KEY TAKEAWAYS
- The KarMMa-3 phase III trial aimed to compare ide-cel and standard therapies for heavily pretreated MM across prior lines.
- The result demonstrated that the ide-cel outperformed standard regimens with similar safety.
Combo therapy accelerates TCE status in relapsed and refractory multiple myeloma (RRMM), creating a treatment gap. KarMMa-3 tested idecabtagene vicleucel (ide-cel) vs. standard options in TCE RRMM, demonstrating significant PFS and ORR improvements with ide-cel.
For this study, researchers aimed to compare ide-cel and standard therapies for heavily pretreated multiple myeloma across prior lines. They also assessed efficacy and safety in subgroups defined by treatment history.
Patients with RRMM who received 2–4 prior lines of therapy (LoT) were TCE (immunomodulatory agents, proteasome inhibitors, and daratumumab) and demonstrated disease refractoriness to the last regimen and were randomized in a 2:1 ratio. They were assigned to receive ide-cel (range 150–450 x 106 CAR+ T cells) or a standard regimen (DPd, DVd, IRd, Kd, or EPd).
Stratification factors included the number of prior lines of therapy (2 vs. 3 or 4). Analysis was done to assess the relationship between soluble BCMA (sBCMA) levels and the number of prior lines of therapy. Baseline characteristics and high-risk clinical features were generally well-balanced across prior LoT in each arm.
The proportion of patients with triple-class–refractory (TCR) disease increased, and the median time to progression on the last prior treatment declined from 2 to 4 before LoT (ide-cel: 50% to 88% and 9.3 to 5.1 months, respectively) for both arms.
Following a median follow-up of 18.6 months (range 0.4–35.4), the progression-free survival (PFS) improvement for ide-cel versus standard regimens was consistent across prior LoT (HR 0.44–0.58).
In patients with 2, 3, or 4 prior LoT, median PFS with ide-cel was 15.1 and 12.0 months, respectively, versus 4.8 and 4.2 months with standard regimens. The 12-month PFS rates in the ide-cel arm were 64%, 54%, and 46% in patients with 2, 3, and 4 prior LoT, respectively.
Ide-cel demonstrated numerically higher overall response rates (69–74% vs. 35–51%) and complete response rates (34–42% vs. 2–13%) compared to standard regimens regardless of prior LoT. Baseline sBCMA levels were similar in patients with 2 vs. 3 or 4 before LoT in both arms; at nadir, a greater proportion of patients in the ide-cel arm with 2 prior LoT cleared sBCMA levels (82% vs. 68%; P=0.0238).
The proportion of patients who faced serious adverse events (AEs) was comparable in subgroups based on prior lines of therapy (LoT) (ide-cel: 51–55%; std regimens: 37–39%) compared to the overall population (ide-cel: 52%; std regimens: 38%).
The safety profile of ide-cel, including cytokine release syndrome (CRS), remained consistent across prior lines of therapy. Grade 5 CRS occurred in 1 patient each in the 2 and 3 prior LoT subgroups. Investigator-identified neurotoxicity was lowest in patients with 2 prior LoT (2, 7%; 3 or 4, 19%).
The result demonstrated that the ide-cel outperformed standard regimens with similar safety.
Clinical Trial: https://clinicaltrials.gov/study/NCT03651128
Manier S. (2023). “Idecabtagene vicleucel (ide-cel) vs standard regimens in patients with triple-class–exposed (TCE) relapsed and refractory multiple myeloma (RRMM): KarMMa-3 subgroup analysis by prior lines of therapy. ” Presented at the 2023 International Myeloma Society Annual Meeting; September 27-30, 2023; Athens, Greece. Abstract- OA-47.
