P-031: 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

Introduction: With use of combination therapy (Tx), patients (pts) with RRMM become TCE earlier in their disease course and represent a therapeutic challenge. In the phase 3 KarMMa 3 trial (NCT03651128), ide-cel significantly improved median progression-free survival (mPFS 13.3 vs 4.4 mo; HR 0.49; P< 0.001) and overall response rate (ORR 71% vs 42%; P< 0.001) vs standard (std) regimens in pts with TCE RRMM who received 2−4 prior lines of Tx (LoT). We assessed efficacy and safety of ide-cel vs std regimens across numbers (no.) of prior LoT (2, 3, 4, and 3 or 4) in pts with TCE RRMM in KarMMa 3.

Methods: Pts with RRMM who received 2–4 prior LoT, were TCE (immunomodulatory agents, proteasome inhibitors, and daratumumab), and had disease refractory to the last regimen were randomized 2:1 to receive ide-cel (range 150–450 x 10ᶺ6 CAR+ T cells) or a std regimen (DPd, DVd, IRd, Kd, or EPd); stratification factors included no. of prior LoT (2 vs 3 or 4). Analysis was performed to assess the relationship between soluble BCMA (sBCMA) levels and prior LoT.

Results: Baseline characteristics and high-risk clinical features were generally balanced across prior LoT in each arm. Proportion of pts with triple-class–refractory (TCR) disease increased and median time to progression on last prior Tx decreased from 2 to 4 prior LoT (ide-cel: 50% to 88% and 9.3 to 5.1 mo, respectively), for both arms. At a median follow-up of 18.6 (range 0.4–35.4) mo, PFS improvement for ide-cel vs std regimens was consistent across prior LoT (HR 0.44–0.58). In pts with 2 and 3 or 4 prior LoT, mPFS with ide-cel was 15.1 and 12.0 mo, vs 4.8 and 4.2 mo with std regimens, respectively. The 12-mo PFS rates in the ide-cel arm were 64%, 54%, 46% in pts with 2, 3, 4 prior LoT, respectively. Ide-cel showed numerically higher ORRs (69−74% vs 35−51%) and complete response rates (34−42% vs 2−13%) vs std regimens regardless of prior LoT. Baseline sBCMA levels were similar in pts with 2 vs 3 or 4 prior LoT in both arms; at nadir, a greater proportion of pts in the ide-cel arm with 2 vs 3 or 4 prior LoT cleared sBCMA level (82% vs 68%; P=0.0238). Proportion of pts who had serious AEs was similar in subgroups by prior LoT (ide-cel 51−55%; std regimens 37–39%) vs the overall population (ide-cel 52%; std regimens 38%). Safety profile of ide-cel including cytokine release syndrome (CRS) was similar across prior LoT. Grade 5 CRS occurred in 1 pt each in the 2 and 3 prior LoT subgroups. Investigator-identified neurotoxicity was lowest in pts with 2 prior LoT (2, 7%; 3 or 4, 19%).

Conclusions: Across prior LoT, the benefit of ide-cel vs std regimens was maintained with consistent safety profile. With increasing LoT, pts were more likely to have TCR disease and numerically poorer efficacy outcomes in both arms. Greater proportion of pts in the ide cel arm with 2 vs 3 or 4 prior LoT had clearance of tumor burden as measured by sBCMA, raising the possibility of earlier ide-cel use in TCE RRMM.
Presented at EHA 2023; P866 (https://library.ehaweb.org).