How I Manage Transplant Ineligible Patients with Myelodysplastic Neoplasms

Abstract

Myelodysplastic neoplasms, formerly known as myelodysplastic syndromes (MDS), represent a group of clonal disorders characterized by a high degree of clinical and molecular heterogeneity, and an invariable tendency to progress to acute myeloid leukemia. MDS typically present in the elderly with cytopenias of different degrees and bone marrow dysplasia, the hallmarks of the disease. Allogeneic hematopoietic stem cell transplant is the sole curative approach to date. Nonetheless, given the disease’s demographics, only a minority of patients can benefit from this procedure. Currently used prognostic schemes such as the Revised International Prognostic Scoring System (R-IPSS), and most recently the molecular IPSS (IPSS-M), guide clinical management by dividing MDS into two big categories: lower- and higher-risk cases, based on a cut-off score of 3.5. The main clinical problem of the lower-risk group is represented by the management of cytopenias, whereas the prevention of secondary leukemia progression is the goal for the latter. Herein, we discuss the non-transplant treatment of MDS, focusing on current practice and available therapeutic options, while also presenting new investigational agents potentially entering the MDS therapeutic arsenal in the near future.

Evolution of Therapeutic Benefit Measurement Criteria in Myelodysplastic Syndromes/Neoplasms

“…Concurrently, the wider use of molecular assessments has identified an increasing number of mutations linked to MDS, some of which (e.g., SF3B1 ) impart a unique disease phenotype and a potential therapeutic biomarker. The implementation of molecular assessments into the diagnostic algorithm of MDS has impacted the classification, risk stratification, treatment, and prognostication of patients with MDS 1,2,16,21 . The recognized limitations of the 2006 criteria and increasing use of molecular assessments to calculate disease risk in routine practice and trials have led to an international group of experts to develop a systematic and evidence-based approach to redefine the IWG response criteria focusing on HR-MDS in 2023 13 .…”

“…The implementation of molecular assessments into the diagnostic algorithm of MDS has impacted the classification, risk stratification, treatment, and prognostication of patients with MDS. 1,2,16,21 The recognized limitations of the 2006 criteria and increasing use of molecular assessments to calculate disease risk in routine practice and trials have led to an international group of experts to develop a systematic and evidence-based approach to redefine the IWG response criteria focusing on HR-MDS in 2023. 13 Here, we review the evolution of therapeutic response assessment definitions for both LRand HR-MDS, their caveats, and potential areas of improvement.…”

What’s Next after Hypomethylating Agents Failure in Myeloid Neoplasms? A Rational Approach

“…Both HMAs have been approved in oral and injectable forms by the Food and Drug Administration (FDA) for specific indications that are not interchangeable in the treatment of myelodysplastic syndromes/neoplasms (MDS) and acute myeloid leukemia (AML) [ 1 , 2 , 3 , 4 ]. While allogeneic hematopoietic cell transplant (Allo-HCT) remains the only potentially curative therapeutic modality for MDS, most patients are older and considered ineligible for intensive therapies such as Allo-HCT, and instead opt for lower-intensity treatments with palliative intent [ 5 , 6 ]. Indeed, AZA demonstrated superior overall survival (OS) vs. conventional care regimens including supportive care, and low or intensive chemotherapy in HR-MDS patients in a randomized trial setting [ 7 , 8 , 9 ].…”