Maintenance lenalidomide in combination with 5‐azacitidine as post‐remission therapy for acute myeloid leukaemia

Abstract

SummaryIn this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0-25 mg, days 5-25) in combination with azacitidine (50-75 mg/m 2 , days 1-5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) (n = 5), age ≥60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose-limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse-free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50% at 24 months. There were five patients with concomitant FLT3-ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17-39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high-risk AML warrants further exploration.

RETRACTED ARTICLE: 5-Azacitidine for treating acute myelogenous leukemia

“…The lenalidomide/ azacitidine maintenance combination was effective in suppressing residual DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A)-positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/ lenalidomide as maintenance therapy for high-risk [70] AML warrants further exploration.…”

Effects of lenalidomide on the bone marrow microenvironment in acute myeloid leukemia: Translational analysis of the HOVON103 AML/SAKK30/10 Swiss trial cohort

“…With respect to the AML-categories, a more substantial blast drop under lenalidomide was noticed in AML with defining mutations, despite the fact that the presence of driver mutations such as FLT3 and NPM1 has been linked to low cytolytic activity of the tumor microenvironment [34]. If this effect is linked to the immune modulatory or other functions of lenalidomide and if it is reproducible in other AML collectives, remains to be determined [35].…”

Biology-Driven Approaches to Prevent and Treat Relapse of Myeloid Neoplasia after Allogeneic Hematopoietic Stem Cell Transplantation

“…These findings are promising, and a larger follow-up study is currently underway. A synergistic effect of the combination of 5-azacytidine and lenalidomide as postremission maintenance outside of allo-HCT was reported in a phase I trial [75], and randomized trials in the prophylactic setting are ongoing (Clinical Trials.gov identifier NCT00887068).…”