P-325: In-class transition from parenteral bortezomib (V) to oral ixazomib in newly diagnosed multiple myeloma (NDMM): Updated 3-year PFS analysis of US MM-6 overall and by patient (pt) subgroups of interest

Introduction: US MM-6 is a prospective, community-based, phase 4 study of in-class transition (iCT) from parenteral V-based induction to all-oral ixazomib-lenalidomide-dexamethasone (IRd) in pts with NDMM (NCT03173092). We report an updated 3-year (yr) PFS analysis of US MM-6.

Methods: Transplant-ineligible/delayed-transplant (≥24 months) NDMM pts with ≥stable disease after 3 cycles of V-based induction were enrolled at US community sites to receive IRd for ≤39 cycles or until progression/toxicity. For this 3-yr PFS analysis, efficacy and safety were assessed overall and by age (< 75 vs ≥75 yrs), frailty status (non-frail vs frail), and randomized controlled trial (RCT) eligibility status (eligible vs ineligible).

Results: At time of data abstraction (Oct 2023), 140 pts had received IRd: 42% were aged ≥75 yrs, 61% were classified as frail, and 41% were RCT-ineligible. Overall median follow-up was 36 months (mos), and 8 pts (6%) were ongoing on study treatment. Among all pts, median duration of therapy (DOT) was 14 mos with all proteasome inhibitor (PI)-based therapy and 11 mos with IRd. The 3-yr PFS rate was 58% overall and median PFS was not reached (NR); 3-yr PFS rates were 65 vs 46% in pts aged < 75 vs ≥75 yrs, 62 vs 55% in non-frail vs frail pts, and 62 vs 52% in RCT-eligible vs -ineligible pts. For all pts, the 3-yr overall survival (OS) rate was 76% and median OS was NR; 3-yr OS rates were 81 vs 67% in pts aged < 75 vs ≥75 yrs, 77 vs 75% in non-frail vs frail pts, and 75 vs 77% in RCT-eligible vs -ineligible pts. Duration of response (DOR) rate was 62% overall and median DOR was NR; 3-yr DOR rates were 71 vs 47% in pts aged < 75 vs ≥75 yrs, 64 vs 60% in non-frail vs frail pts, and 66 vs 55% in RCT-eligible vs -ineligible pts. The overall response rate (ORR) increased from 62% at the end of V-based induction to 80% following iCT to IRd, with similar increases across subgroups (60 to 80% vs 64 to 80% in pts aged < 75 vs ≥75 yrs, 70 to 81% vs 57 to 79% in non-frail vs frail pts, and 64 to 80% vs 60 to 81% in RCT-eligible vs -ineligible pts; ≥VGPR rates increased from 32 to 64% overall. Of all 140 pts, 99% reported ≥1 TEAE, with similar rates across subgroups. Grade ≥ 3 TEAEs occurred in 70% overall, and in 70 vs 69% of pts aged < 75 vs ≥75 yrs, 61 vs 76% of non-frail vs frail pts, and 66 vs 75% of RCT-eligible vs -ineligible pts.

Conclusions: In non-transplant pts with NDMM, iCT from V-based induction to all-oral IRd permits long-term PI-based treatment and improves depth of response while maintaining a tolerable safety profile. The expected decrement in outcomes associated with older, frail, and RCT-ineligible pts was observed; however, these results were not meaningfully different. Long-term triplet consolidation with IRd may provide an alternative approach to induction/maintenance for community-based NDMM pts who are not eligible for upfront transplantation, including those who are older, frail, and/or have comorbidities.
This abstract was accepted and presented at the EHA 2024 Congress.