Isatuximab, bortezomib, lenalidomide, and dexamethasone (Isa-VRd) in newly diagnosed multiple myeloma (NDMM): Outcomes in patients with 1q21+ status in the phase 3 IMROZ study.

7517 Background: Gain or amplification of 1q21 (1q21+, ≥3 copies) is a chromosomal abnormality often detected in MM that can negatively affect prognosis by its involvement in resistance to therapy and MM progression. Results from the global, randomized Phase 3 IMROZ study (NCT03319667) demonstrated significant progression-free survival (PFS) benefit with Isa-VRd followed by Isa-Rd compared with VRd followed by Rd, along with deep and sustained responses, in transplant-ineligible patients (pts) with NDMM. To evaluate efficacy of combination treatment with Isa-VRd/Isa-Rd vs VRd/Rd in NDMM pts with 1q21+ status, we analyzed clinical outcomes (PFS, overall response, minimal residual disease negativity [MRD–]) for 1q21+ pts in the IMROZ study. Methods: In IMROZ, 446 pts were randomized 3:2 to receive Isa-VRd (n=265) in the initiation phase followed by maintenance with Isa-Rd vs VRd (n=181) followed by Rd. 1q21+ status was assessed by FISH (30% cutoff) and prespecified as ≥3 copies (gain=3, amplification >3). Isolated 1q21+ was defined as presence of 1q21+ and absence of high-risk chromosomal abnormalities [HRCAs; del(17p), t(4;14), t(14;16)]. MRD data by NGS were reported at 10 -5 sensitivity threshold. Results: Overall, 35.9% and 38.7% of pts had 1q21+ status in the Isa-VRd and VRd arms, respectively (23.8% and 26.0% with gain(1q21), 12.1% and 12.7% with amp(1q21); 7.2% and 8.3% also had ≥1 HRCA). Treatment with Isa-VRd significantly prolonged PFS vs VRd in 1q21+ pts (with or without HRCA) and in pts with isolated 1q21+ (see Table) and led to higher rates of complete response (CR) and MRD–. A substantially greater proportion of pts with 1q21+ or isolated 1q21+ achieved MRD– CR and sustained MRD– for ≥12 months with Isa-VRd than with VRd. Data for gain(1q21) and amp(1q21) will be presented. Conclusions: Results from our analysis of outcomes in 1q21+ pts in the IMROZ trial demonstrate consistent PFS benefit with Isa-VRd vs VRd, as reported in the overall study population. Benefit was observed regardless of 1q21+ or isolated 1q21+ status.These findings are in line with similar analyses done with Isa-pomalidomide-dexamethasone and Isa-carfilzomib-dexamethasone in Phase 3 studies. Clinical trial information: NCT03319667 . 1q21+ Isolated 1q21+ a Standard risk a Isa-VRd VRd Isa-VRd VRd Isa-VRd VRd n (%) 95 (35.9) 70 (38.7) 75 (28.3) 55 (30.9) 207 (78.1) 140 (77.4) mPFS, mo(95% CI) NR(NR–NR) 39.13(22.93–48.95) NR(NR–NR) 43.01(20.60–59.70) NR(NR–NR) 53.91(43.01–NR) PFS HR (95% CI) 0.407 (0.253–0.653) p =0.0002 0.369 (0.213–0.642) p =0.0004 0.517 (0.363–0.737) p =0.0003 ORR % 95.8 85.7 96.0 81.8 97.5 100 ≥CR % 76.9 60.0 78.7 52.7 72.5 79.4 MRD– % 63.2 41.4 65.3 40.0 58.9 40.7 MRD– CR % 62.1 38.6 64.0 36.4 55.6 37.9 Sustained MRD– ≥12 mo % 51.6 22.9 50.7 23.6 45.4 22.9 a Absence of del(17p), t(4;14) and t(14;16). NR, not reached.