Iberdomide (Iber) maintenance following upfront autologous stem cell transplant (ASCT) in multiple myeloma (MM).

Abstract

7528 Background: Lenalidomide (Len) maintenance after ASCT has been a standard of care for patients (pts) with MM. Historically, ~30% of pts discontinue Len within 1 year (yr) due to toxicity and there is a need for more effective and better tolerated maintenance strategies. Iber is a potent, oral cereblon E3 ligase modulator under evaluation in the relapsed/refractory and newly diagnosed settings. We report the results of the primary analysis of a Phase II trial of Iber maintenance following upfront ASCT. Methods: Pts ≥ 19 yrs of age with MM, within 1-yr of initiation of induction therapy and in a ≥ partial response (PR) at day 80-110 post-ASCT, were accrued. Iber was administered 1.0 mg orally days 1-21 of a 28-day cycle, continued until progressive disease (PD) or toxicity. Up to 2 dose reductions (0.75 mg/day then 0.6 mg/day) were allowed. Growth factor support was not permitted. Minimal residual disease (MRD) assessment by flow cytometry (10 -5 ) was performed at registration, post-cycle 12 and post-cycle 24. An optimal Simon two-stage design with type I and II errors of 0.1 was chosen to test whether the proportion of pts who are progression-free and on treatment at 1 yr is <60% against the alternative of ≥ 80%. If ≥ 27 out of 38 pts were progression-free (by 2016 IMWG criteria) and on treatment at 1 yr, Iber would be considered to have promising activity. Results: 38 pts (55% males, median age 61 yrs (range: 41-77)) received Iber. R-ISS at diagnosis was stage I (34%), II (39%), III (8%) and unknown (18%), with 34% having high-risk disease per 2025 IMS/IMWG criteria. All pts received triplet or quadruplet induction therapy, with 97% receiving Len and 84% receiving daratumumab. At day 80-110 post-ASCT, all pts had ≥ very good PR, with 22 (58%) ≥ complete response (CR) and 33 (87%) MRD-negative (neg). The median number of administered treatment cycles is 18 (range: 1-45), with 18 (47%) pts having ≥ 1 dose reduction, most commonly due to neutropenia (n=12). The most common grade (gr) 3/4 adverse event was neutropenia (gr 3 (n=19), gr 4 (n=5)). Within yr 1, 29% (11/38) discontinued Iber due to neutropenia (n=5), rash (n=1), infection (n=1), pt choice (n=1), or PD (n=3). After 1 yr, 6 pts discontinued due to neutropenia (n=4) and PD (n=2). While on Iber, 19 pts had deepening of response to stringent CR and 3 pts converted from MRD-positive to MRD-neg. The post-cycle 12 and 24 MRD-neg rates are 85% (23/27) and 100% (14/14), respectively. Conclusions: Iber demonstrated promising activity with dose reductions/discontinuations mainly due to neutropenia. Strategies including lower starting dose, growth factor support and more flexible management of neutropenia may enable more pts to remain on treatment. Longer follow-up will permit evaluation of sustained MRD-negativity and PFS, but overall, these results provide rationale for further exploration of Iber-based post-ASCT maintenance strategies. Clinical trial information: NCT05177536 .