Maintenance lenalidomide in combination with 5‐azacitidine as post‐remission therapy for acute myeloid leukaemia. (2nd February 2015)

• Record Type: Journal Article
• Authors: Wei, Andrew; Tan, Peter; Perruzza, Sarah; Govindaraj, Chindu; Fleming, Shaun; McManus, Julie; Avery, Sharon; Patil, Sushrut; Stevenson, William; Plebanski, Magdalena; Spencer, Andrew
• Is Part Of: British journal of haematology. Volume 169:Number 2(2015:Apr.)
• Page Start: 199
• Page End: 210
• Publication Date: 2015-02-02
• Subjects: Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13281
• Languages: English
• ISSNs: 0007-1048

Abstract

<abstract abstract-type="main" id="bjh13281-abs-0001"> <title>Summary</title> <p>In 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<sup>2</sup>, 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 (<italic>n</italic> = 8), fms‐related tyrosine kinase 3‐internal tandem duplication (<italic>FLT3</italic>‐ITD) (<italic>n</italic> = 5), age ≥60 years (<italic>n</italic> = 31) or AML in second remission (CR2) (<italic>n</italic> = 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 <italic>FLT3</italic>‐ITD and nucleophosmin (<italic>NPM1</italic>) 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 <italic>NPM1</italic> 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 <italic>NPM1</italic> mutation. Azacitidine/lenalidomide as maintenance therapy for high‐risk AML warrants further exploration.</p> </abstract>