Carfilzomib, iberdomide, and dexamethasone (KID) in patients with transplant-eligible newly diagnosed multiple myeloma (NDMM): Updated results from phase 1/2 study.

7553 Background: SOC regimens for patients (pts) with transplant-eligible NDMM include VRd, D-VRd, and KRd. Iberdomide, a cereblon modulator, enhances immune stimulatory activity in vitro compared to thalidomide analogs. A phase 1 study reported the MTD of iberdomide 1.6 mg plus carfilzomib (CFZ) and dexamethasone (DEX), KID regimen, in NDMM pts (Biran 2023). Herein we report longer term safety and efficacy data from a phase 2 dose expansion study of KID in NDMM pts (NCT05199311). Methods: Adults with NDMM eligible for ASCT were enrolled in this multicenter, investigator-initiated phase 1/2 study. In the phase 2 portion, pts received CFZ (IV; 20 mg/m 2 on C1D1; then 56 mg/m 2 C1 D8, 15; then 56 mg/m 2 C2-4 D1, 8, 15), iberdomide (1.6 mg; D1-21), and DEX (40 mg if ≤75 years; 20 mg if >75 years; D1, 8, 15) in 28-day cycles for 2-3 cycles followed by ASCT. The primary objective is to evaluate the rate of CR + sCR. Results: As of 1/10/25, 38 pts signed consent, including 20 in follow-up, 7 off study (5 screen failures/1 consented/1 withdrew due to rash), and 4 on treatment (tx). Of 31 pts who received tx, median age was 66 years (range 41-78), 52% male, 77% White, 16% Black, 3% Asian, 58%/16%/6% ISS stage 1/2/3, respectively. Thirteen pts (42%) had high-risk cytogenetics: t(4;14) (n=3), t(4;16) (n=1), del(17p)/monosomy 17/ TP53 (n=2), 1q21 (n=9), and MYC (n=1). Two pts had double- and 1 was triple-hit MM. Thirty-one pts completed a median of 3 cycles (range 1-4) of KID. At end of induction, ORR was 96% (23/24, CR 4%, VGPR 42%, PR 50%). Twenty-three pts proceeded to ASCT; 8 did not (4 on tx/1 collecting cells/1 withdrawal/1 death). Median number of stem cells mobilized was 11.3 x 10 6 cells/kg (range 4.74-29.8). At 3 months post-ASCT, ORR was 100% (19/19, sCR 5%, CR 21%, VGPR 53%, PR 21%), CR + sCR is 26%, and of those, 100% are MRD-negative. Median tx duration was 84 days (IQR, 63-91). At median follow-up of 12.4 months, median PFS and OS were NR (95% CI, NA-NA). Most common hematologic TEAEs were anemia (19%), neutropenia (39%), and thrombocytopenia (23%). Most common non-hematologic TEAEs were pruritus (23%) and rash (23%). Grade 3 TEAEs occurred in 26% of pts; most common were neutropenia (26%), thrombocytopenia (6%), and rash (6%). Six pts developed grade 1-2 SAEs unrelated to tx. One patient experienced grade 3 SAE of fever and colonic hemorrhage that required hospitalization and supportive care. No tx-related deaths occurred; 1 patient died on study due to a possible thrombotic event in the setting of medication non-compliance. Conclusions: Induction therapy with KID appears safe and effective leading to deep responses and adequate stem cell collection despite short tx duration and 42% harboring high-risk cytogenetics. Long-term follow-up is needed to determine durability of response. Correlative studies are underway to evaluate immune phenotype and microbiome changes pre/post-tx. Clinical trial information: NCT05199311 .