A phase 1 dose-escalation study of low-dose lenalidomide maintenance post-allogeneic stem cell transplantation for high-risk acute myeloid leukaemia or myelodysplastic syndrome

Abstract Immunomodulatory strategies to promote the graft-versus-leukaemia (GVL) effect following allogeneic stem cell transplantation (alloSCT) may precipitate graft-versus-host-disease (GVHD). We hypothesise that low-dose lenalidomide may be tolerable whilst still being able to augment GVL. We conducted a phase 1 study of post-alloSCT low-dose lenalidomide maintenance for patients with high-risk acute myeloid leukaemia or myelodysplastic syndrome. The primary objective was to determine the maximum tolerated dose (MTD). Secondary objectives were treatment efficacy and assessment of immune reconstitution. Lenalidomide was commenced from day 40–45 post-alloSCT for up to 12 months. Fifteen patients were recruited. The highest lenalidomide dose was 5mg alternate daily, however the MTD was not reached due to early study termination from poor recruitment. Four dose-limiting toxicities were encountered, of which 3 were grade III acute GVHD. Of the 6 patients who died, 5 were due to relapsed disease. The incidence of acute GVHD was 33% and chronic GVHD at 1-year was 19%. One-year relapse-free survival and overall survival were 60%. Despite the low dose of lenalidomide, NK and T cell immune reconstitution was improved at day 100 post-alloSCT. Low-dose lenalidomide maintenance post-alloSCT resulted in acceptable GVHD risks with demonstrable impacts on immune reconstitution, meriting further investigation as a relapse-prevention strategy.