(PA-524) Iberdomide Maintenance after Autologous Hematopoietic Cell Transplant for Patients who Previously Received Lenalidomide Maintenance

Introduction: Delaying autologous hematopoietic cell transplantation (aHCT) consolidation and proceeding straight to lenalidomide maintenance has become more common as patients derive deeper remissions from initial therapy for multiple myeloma (MM). Therefore, a maintenance strategy is needed after melphalan and salvage aHCT. Iberdomide (iber) is a next-generation CELMoD with higher potency than lenalidomide, and we aimed to determine its benefit as maintenance.

Methods: Cohort 2 of this phase II trial (NCT05354557) enrolled patients who previously had lenalidomide maintenance and received a salvage aHCT after progressing on 2-3 prior lines of therapy (LOT) counted by progressions. Iber was given as 1 mg orally on days 1-21 of 28-day cycles for up to 12 cycles, with continuation of treatment if patients had not progressed.

Results: Cohort 2 enrolled 15 patients (median age 61 years [47-74], 67% female) after a median of 2 prior LOT (2-3). 73% were triple-class refractory and 66% had high-risk cytogenetics. The majority (80%) had deferred aHCT consolidation, while 20% had a second aHCT. Median time from MM diagnosis to salvage aHCT was 42 mo (30-164), and median time from aHCT to starting iber was 3.4 mo (2.8-4.9). Disease status prior to salvage aHCT was 27% untreated progressive disease (PD), 13% stable disease (SD), 33% partial response (PR), and 27% very good PR (VGPR). When starting iber, patients had SD, PR, VGPR, CR with positive measurable residual disease by 10-5 flow (MRD+), and CR without measurable residual disease (MRD-) in 13%, 33%, 13%, 33% and 7% of cases, respectively. All patients are alive with a median follow-up of 15.4 months from starting iber, and 30% (n=4) remain on treatment with iber with sustained responses past the 12-mo mark. Patients not assessed at the 3-mo mark included those who withdrew from the study due to grade 1 rash (n=1), travel plans (n=1) and early progression (n=1). 8 patients discontinued iber due to PD. Median time to progression post iber was 7.4 mo (3-18.6). Median time to best response to iber was 3.5 mo (3.2-7) with 25% (n=3), 25% (n=3), 25% (n=3) and 25% (n=3) achieving SD, PR, VGPR, and MRD neg CR, respectively. Median PFS from starting iber was 9.3 mo (6.7–NR), median OS was not reached. CTCAE grade 3 toxicities included neutropenia (n=1), rash (n=2), and infections (n=3). No grade 4/5 toxicities occurred.

Conclusions: Iber maintenance after salvage aHCT in patients with MM who had prior lenalidomide maintenance was overall well tolerated without unexpected or high-grade adverse events. Changes in immune function over time will also be reported. Iber allowed for a prolonged benefit in a high-risk population, as initiation of maintenance around 3 months post salvage aHCT resulted in a median of more than one year before requiring further LOT. These results support further investigation of iber as a maintenance strategy in patients who have progressed on lenalidomide maintenance.