OA – 50: Phase II study of iberdomide maintenance therapy post-autologous stem cell transplant in multiple myeloma: results of a planned interim analysis

Introduction: Lenalidomide maintenance therapy following autologous stem cell transplant (ASCT) is a standard of care for patients (pts) with multiple myeloma (MM). However, nearly all pts will experience disease relapse. Historically, lenalidomide’s toxicity profile has led to treatment discontinuation in ~30% of pts by one year (yr). Thus, more effective and better tolerated maintenance therapies are needed. Iberdomide (IBR) is a novel potent cereblon E3 ligase modulator. We report the results of a planned interim analysis of a Phase II trial assessing IBR maintenance therapy after upfront ASCT in MM.

Methods: Pts > 19 yrs of age with active MM, within 1-yr of initiation of induction therapy and in a continued > partial response at day 80-110 post-ASCT were accrued. Disease assessment included bone marrow minimal residual disease (MRD) via flow cytometry (10^-5) performed at a central lab. IBR was administered 1.0 mg orally on days 1-21 of a 28-day cycle. Up to 2 dose reductions (0.75 mg/day then 0.6 mg/day) were allowed. The trial design is a one-stage phase II study with a futility stopping rule to assess whether the proportion of pts who complete at least 1-yr of IBR is at least 80%. The primary objective is to estimate the proportion of pts who complete at least 1 yr of IBR. A planned interim analysis with a futility stopping rule was conducted once the first 11 pts had either been on treatment for 1-yr or had discontinued treatment for any reason prior to 1-yr. If < 6/11 pts completed at least 1 yr of IBR, then study enrollment would cease.

Results: Seven males and 4 females (age range 46-64 yrs, median 58) composed the interim analysis cohort. R-ISS stage at diagnosis was I (n=2), II (n=5), III (n=2) and unknown (n=2) with 4 pts having high-risk disease (del(17p): n=2 ; t(4;14): n=2). The day 80-110 post-ASCT assessment revealed 100% > very good partial response rate, with 73% > complete response (CR) and 82% MRD-negative (neg). The median number of treatment cycles completed thus far is 18 (range: 12 – 24). Four pts required a dose reduction due to grade (gr) 3 decreased neutrophil count (n=2), gr 3 pneumonia (n=1) or gr 3 maculo-papular rash (n=1). Gr 2/3 treatment-related adverse events included decreased neutrophil count (n=1 (gr 2), n=5 (gr 3)), febrile neutropenia (n=1 (gr 3)), rash (n=1 (gr 3)), anemia (n=1 (gr 2)), COVID-19 (n=1 (gr 2)), diarrhea (n=1 (gr 2)), gastrointestinal infection (n=1 (gr 2)), pneumonia (n=1 (gr 2)), thromboembolic event (n=1 (gr 2)). No pts have discontinued protocol treatment; the stringent CR rate is 100% with MRD-neg rate of 91% after 1 yr of IBR. Thus, the trial will continue.

Conclusions: This interim analysis demonstrates the feasibility, safety and promising activity of IBR maintenance following upfront ASCT and enables continuation of the trial. Enrollment is ongoing and longer follow-up is required to determine rates of sustained MRD-negativity, treatment duration and progression-free survival.