Phase II trial of maintenance therapy with iberdomide after autologous hematopoietic cell transplant for patients with multiple myeloma previously treated with lenalidomide

Abstract

Abstract Background Lenalidomide maintenance after upfront autologous hematopoietic cell transplantation (aHCT) has improved progression free survival (PFS) and overall survival (OS) of patients with multiple myeloma (MM). Currently, modern induction therapies with deep responses allow patients to elect to defer aHCT. A maintenance strategy is needed after melphalan and salvage aHCT in patients previously treated with lenalidomide. Iberdomide is a next-generation CELMoD with higher potency than lenalidomide and pomalidomide, and we aimed to determine the benefit of this agent as maintenance post salvage aHCT. Methods This phase II trial (NCT05354557) enrolled patients into two cohorts. Cohort 1: Patients within 15 months (mo) post-frontline aHCT who achieved ≤ very good partial response (VGPR) despite ≥6 mo of lenalidomide maintenance. Cohort 2: Patients undergoing salvage aHCT following progression on lenalidomide maintenance after 2-3 prior lines of therapy (LOT). All patients received iberdomide 1 mg orally on days 1–21 of 28-day cycles for up to 12 cycles, with continuation in patients without disease progression. The primary objective was to estimate the complete response (CR) rate to iberdomide treatment. Secondary objectives included estimation of measurable residual disease negativity (MRD–) by 10-5 flow cytometry, PFS, OS, and incidence of CTCAE grade 3–5 toxicities. Results We report the results for cohort 2 (n=15, median age of 61 years [47-74], 67% female). Patients received a median of 2 prior LOT (2-3); 73% were triple-class refractory; 66% had high-risk cytogenetics; 20% had prior aHCT and 80% had deferred upfront aHCT. Median time from MM diagnosis to aHCT was 42 mo (30-164), and median time from aHCT to treatment with iberdomide was 3.4 mo (2.8-4.9). Disease status before salvage aHCT was: 27% untreated progressive disease (PD), 13% stable disease (SD), 33% partial response (PR) and 27% VGPR. Disease status before iberdomide treatment included: 14% SD, 33% PR, 13% VGPR, 33% CR/measurable residual disease positive (CR/MRD+), and 7% CR/MRD-. At a median follow-up of 15.4 mo, all evaluable patients (n=15) are alive. 2 patients withdrew from the study (1 due to grade 1 rash and 1 due to personal preferences). 1 patient progressed before their 3-mo assessment. 8 patients discontinued treatment due to PD, with a median time to progression of 7.4 mo (3-18.6). 4 patients remain on iberdomide with responses lasting >12 mo. Best responses to iberdomide were CR/MRD- in 25% of patients (n=3), VGPR in 25% (n=3), PR in 25% (n=3) and SD in 25% (n=3). Median time to best response from initiation of iberdomide was 3.5 mo (3.2-7). Median PFS from starting iberdomide was 9.3 mo (6.7-NR). Median OS has not been reached. CTCAE grade 3 toxicities were neutropenia (n=1), maculopapular rash (n=2), and infections (n=3). There were no grade 4 or 5 toxicities. Conclusion Iberdomide maintenance following salvage aHCT demonstrated clinical activity in a cohort of high-risk MM patients who had been previously treated with lenalidomide. The heterogeneity of responses in later lines of treatment was evident, as demonstrated by the subset of patients who have experienced deep and long-lasting responses to iberdomide. As patients started maintenance around 3 months after transplant, the use of iberdomide allowed for a median of more than one year prior to needing additional therapy. Treatment was generally well tolerated, with no grade 4 or 5 toxicities observed, and without new side effects other than those seen with IMiDs. Changes in immune function over time will also be reported. Overall, these outcomes support further investigation of iberdomide as a maintenance strategy for patients in the salvage setting and with lenalidomide refractoriness.