Douglas A. Tremblay, MD, assistant professor, medicine, Icahn School of Medicine at Mount Sinai, discusses the prevalence of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes and the evolving treatment paradigm for these diseases, which he discussed in a presentation at the 41st Annual CFS®.
MDS/MPN overlap syndromes include a cluster of 4 related diseases: chronic myelomonocytic leukemia (CMML); atypical chronic myeloid leukemia; MDS/MPN with ring sideroblasts and thrombocytosis; and unclassifiable MDS/MPN, Tremblay says. These diseases are often difficult to manage because they share many characteristics that are indicative of both myeloproliferative diseases and MDS, Tremblay notes. Although these conditions are considered rare, they are likely more prevalent than initially hypothesized because of the overlapping nature of MPNs and MDS, Tremblay explains. However, treatment decisions for patients with these overlap syndromes are typically influenced by insights garnered from the MDS and MPN treatment paradigms, Tremblay emphasizes. In the future, the management of these overlap syndromes may become more specialized, Tremblay says. Tailored therapies are emerging, particularly in the CMML field, where JAK inhibitors have gained prominence, Tremblay explains.
Treatment decisions for patients with MDS/MPN overlap syndromes are largely based on the main issue patients experience, such as cytopenias, splenomegaly, or constitutional syndromes, Tremblay notes. Overall, patients with high-risk disease should be referred to autologous stem cell transplant because it is the only curative therapy for these syndromes, Tremblay says. Conversely, many of the treatment strategies for patients who are ineligible for transplant, such as hypomethylating agents (HMAs), are borrowed from the MDS/MPN treatment paradigms, Tremblay explains. However, HMAs have displayed limited efficacy in this population, Tremblay emphasizes. For instance, the phase 3 DACOTA trial (NCT02214407) showed no difference in event-free survival (EFS) or overall survival (OS) with decitabine vs hydroxyurea in patients with a myeloproliferative subtype of CMML.
Efforts to find effective therapies for patients with MDS/MPN overlap syndromes beyond HMAs have spurred research with JAK inhibitors in patients with CMML, according to Tremblay. The JAK-STAT signaling pathway is hypersensitive in CMML cells, and preclinical studies have shown the efficacy of halting that pathway, Tremblay says. Furthermore, a phase 1/2 trial (NCT03722407) showed the advantages of using ruxolitinib (Rituxan) to improve spleen and symptom responses in patients with CMML. Further research is investigating JAK inhibitors in combination with HMAs in patients with CMML and other MDS/MPN overlap syndromes, Tremblay concludes.