A Phase 1/2 Study of Carfilzomib, Iberdomide and Dexamethasone (KID) in Patients with Newly Diagnosed Transplant-Eligible Multiple Myeloma
At data cutoff (July 14, 2023), there were 13 patients enrolled, which included 11 and 2 patients enrolled in the phase 1 and 2 studies, respectively. Ten patients are on trial, 2 were screen failures, and 1 is in screening. Of the 10 patients on trial, the median age was 66 years (range 46-78), 40% male, 70% white, and 30% had ISS stage II MM. Four unique patients had high-risk cytogenetics, which included 2 patients with t(4;14), 2 with 1q21 duplication, 1 with t(14;16), 1 with del(17p)/monosomy 17, and 1 with TP53 mutation.
In the phase 1 study, 3 patients enrolled at the starting dose level of iberdomide 1 mg. Grade 1-2 TEAEs occurred in all 3 patients, but no DLTs occurred. The next 3 patients were enrolled at the iberdomide dose of 1.3 mg. Grade 1-2 TEAEs occurred in 2 patients (rash and pruritus), but no grade ≥3 TEAEs were observed. Three patients were enrolled into the final dose level of iberdomide 1.6 mg. Grade 1-2 TEAEs occurred in 2 patients, and 2 patients experienced grade 3 TEAEs (rash and neutropenia). As no DLTs occurred, the MTD of iberdomide was determined to be 1.6 mg given in combination with CFZ and DEX.
Patients on trial (n=10; 6 in follow-up and 4 actively receiving treatment) have completed a median of 3 (range 2-4) cycles of KID. Of these patients, 7/10 experienced TEAEs (Table 1). No treatment-related deaths occurred. The most common TEAEs were maculopapular rash (46%), elevated liver function tests (38%), gastrointestinal symptoms (31%), and neutropenia (23%). Grade 3 TEAEs occurred in 2 patients (rash and neutropenia). One patient experienced a SAE of erythema multiforme on two separate occurrences (grade 1 and grade 2), which resolved with drug interruption. In 9 patients with response data available, the best ORR was 100% (CR, 1 [12%]; very good partial response [VGPR], 4 [44%]; partial response [PR], 4 [44%]). Six patients proceeded to ASCT with a median amount of stem cells mobilized of 9.42 x 106 cells/kg (range 4.84-13.53). At 3-months post-ASCT, the ORR was 100% (CR, 3 [50%]; VGPR, 2 [33%]; PR, 1 [17%]). One patient had documented sCR and MRD-negativity at data cutoff. Median PFS was not reached (NR) (95% CI, NR-NR).