Incidence of drug-induced myelosuppression and associated adverse events (AEs), quality of life (QOL), and medical resource use (MRU) in myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
Authors: Vutcovici Nicolae Maria , Dong Mei , Jhaveri Teraneh Z. , De Benedetti Laura , Khoury Hanane , Stern Lee , Williamson Mellissa , Beal Jason , Radford Matthew , Chen Mindy , Sun Siu-Chi Chang , Rustia Evelyn Lipana , Schulz Mathias , Ramsingh Giridharan , Sabate Eduardo J 
Published: June 2023

e19072

Background: This study aimed to provide a comprehensive overview of the evidence available on drug-induced myelosuppression in patients with MDS or AML. Methods: A systematic literature review (SLR) was conducted using MEDLINE, Embase, and Cochrane to identify studies published 2002-2022 explicitly targeting drug-induced myelosuppression with current and emerging treatments used for MDS and/or AML (venetoclax [VEN], azacitidine [AZA], magrolimab, sabatolimab, decitabine [DEC], cedazuridine, lenalidomide [LEN], low-dose cytarabine [LDAC], intensive chemotherapy [IC]) in terms of drug-induced AEs, treatment discontinuation, QOL, and MRU. Article selection was based on predefined eligibility criteria (PICO+ framework), with a focus on specific geographic regions (USA, UK, Spain, Italy, France, Germany). Results: A total of 48 studies reporting on VEN, AZA, DEC, LEN, LDAC, and IC based regimens met the inclusion criteria. In MDS populations, myelotoxicity was reported in all blood cell lineages in association with AZA, DEC, and LEN monotherapies. In AML populations, myelosuppression was reported in all blood cell lineages in association with all regimens except LEN. In general, the reported incidence of myelosuppressive AEs was higher in studies published prior to 2010 and in studies of patients with AML or MDS who had received prior treatments vs more recent studies (2018-2022) and studies of treatment-naive patients, respectively. Differences observed between the two time periods might be explained by improved supportive care (AEs prophylaxis and management). In treatment-naive AML populations, the incidence of any-grade febrile neutropenia, leukopenia, and anemia was up to 3-fold higher with AZA combination therapy vs monotherapy, and the incidence of any-grade neutropenia and febrile neutropenia was 2-fold higher with LDAC combination regimens vs monotherapy, suggestive of an additive effect. The most common reasons for treatment discontinuation were AEs and disease progression. QOL significantly improved with AZA monotherapy; however, hematologic improvement was not explicitly mentioned as the main driver. There were no data on combination therapies to indicate whether the improvement in QOL compensated for the added drug-induced AEs. The few studies that reported on the impact of myelosuppression on MRU did not provide conclusive results. Conclusions: This SLR suggests that combining ≥2 myelosuppressive drugs may result in increased toxicity; however, the lack of evidence on the impact of myelotoxicity on QOL and MRU with ≥2 myelosuppressive drugs limits informed decision-making in routine clinical practice. Further research is needed to explore the impact of drug-induced myelosuppression in patients with MDS or AML.