ABSTRACT Although allogeneic hematopoietic stem cell transplantation (allo‐HCT) is considered a potentially curative therapy for multiple myeloma, disease progression after allo‐HCT remains a major limitation. Post‐transplant maintenance therapy may help reduce the risk of relapse. Lenalidomide, an immunomodulatory agent, has demonstrated efficacy in multiple myeloma, but its use after allo‐HCT is limited due to concerns regarding graft‐versus‐host disease (GVHD). To evaluate the maximum tolerated dose (MTD) and dose‐limiting toxicity (DLT) of lenalidomide when used as maintenance therapy after allo‐HCT for multiple myeloma. This was a prospective, multicenter, phase I/II clinical trial conducted from 2014 to 2019. Lenalidomide maintenance therapy was initiated 100–365 days post‐allo‐HCT. Eligible patients received lenalidomide on days 1–21 of a 28‐day cycle for at least four cycles, beginning at 5 mg/day. A standard 3 + 3 dose‐escalation design (Fibonacci method) was used to determine DLT and MTD. The study included 10 patients; one was excluded due to early disease progression, leaving nine patients evaluable for toxicity. The phase II portion was not conducted due to expiration of the trial period. The median interval from allo‐HCT to initiation of lenalidomide was 244 days (range, 169–330 days). At the 10 mg/day dose level, one patient experienced moderate chronic GVHD meeting the predefined criteria for DLT. No other DLTs occurred, establishing the MTD at 10 mg/day. No acute GVHD was observed. Two additional patients developed mild chronic GVHD, which resolved spontaneously without treatment. The 2‐year progression‐free survival (PFS) and overall survival (OS) rates from the start of maintenance therapy were 53% and 78%, respectively. Late initiation of lenalidomide maintenance therapy after allo‐HCT for multiple myeloma was feasible at a dose of 10 mg/day and was associated with a low incidence of GVHD‐related complications. However, further studies are required to confirm treatment efficacy.
Kawamura et al. (Sun,) studied this question.