Treatment of Anemia in Transfusion-Dependent and Non-Transfusion-Dependent Lower-Risk MDS: Current and Emerging Strategies

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow disorders with a highly diverse clinical course. For lower-risk MDS patients, therapeutic objectives aim to correct chronic anemia and improve/maintain health-related quality of life (HRQoL). However, disease burden is often insufficiently recognized, and although some patients do not respond/lose response to standard treatment, many are treated late. This is the case for non-transfusion-dependent patients with symptomatic anemia, in whom delayed treatment initiation may lead to unnecessary morbidity. Current active treatment options for lower-risk MDS are limited. Standard care for lower-risk 5q deletion [del(5q)] MDS patients with anemia remains supportive, consisting of red blood cell (RBC) transfusions, iron chelation therapy, and treatment with erythropoiesis-stimulating agents (ESAs) in the case of low serum erythropoietin levels. Response rates to ESAs range from 15% to 63%, whereas 56% to 67% of patients with del(5q) MDS achieve RBC transfusion independence with lenalidomide. Treatment options for patients' refractory to ESAs and/or lenalidomide, however, are limited. Frequent transfusions are associated with profound clinical, HRQoL, and economic consequences for transfusiondependent patients. This review focuses on the multiple unmet clinical needs that exist in the treatment of anemia associated with lower-risk MDS and the current and future treatment options that may improve disease management and patient outcomes.This study was sponsored by Celgene Corporation, Summit, NJ, USA. UG reports speakers' honoraria from Amgen, Celgene Corporation, Janssen, and Novartis, and research support from Celgene Corporation and Novartis. ENO reports consultancy, honoraria, royalties, and membership on advisory boards for Celgene Corporation, and membership on advisory boards for Amgen, Apellis, Janssen, and Novartis. DH reports research grants from Celgene Corporation and Novartis Australia. AA reports membership on the speakers' bureau and serving on advisory boards for Celgene Corporation and Novartis.

Analysis of Intratumoral Heterogeneity in Myelodysplastic Syndromes with Isolated del(5q) Using a Single Cell Approach

“…To date, lenalidomide has been approved in Europe for the treatment of low-risk transfusion-dependent patients with MDS del(5q), when other therapeutic options are insufficient or inadequate [ 33 ]. Even when 56% to 67% of patients achieve transfusion independence, after 2–3 years of treatment, clinical and cytogenetic relapse might appear in 50% of cases [ 3 , 33 , 34 , 35 ]. In our study, patients P2, P3 and P4 received lenalidomide, while patient P1 did not receive treatment (placebo arm in the SINTRA-REV clinical trial).…”

Red blood cell transfusion in myelodysplastic syndromes: A systematic review

“…Organ dysfunction (liver, cardiac and endocrine, among others) secondary to iron deposition in a chronically transfused MDS patients has important morbidity and mortality implications. 47 Though iron chelation therapy may help to reduce the risks of end-organ dysfunction from iron toxicity, 3,47,48 minimizing excessive RBC transfusion is an important consideration.…”

Analysis of the impact of adherence to guidelines and expert advice in patients with myelodysplastic syndromes

“…Palliative treatment should thus not be undervalued. If transfusion independency is achieved, this will greatly improve the patients' quality of life and also decrease the risk of cardiovascular complications associated with chronic transfusion therapy in MDS [11,12].…”