Treatment advances for pediatric and adult onset neoplasms with monocytosis.

Abstract

For decades, the management of chronic myelomonocytic leukemia (CMML) or juvenile myelomonocytic leukemia (JMML) has been largely inextricable from myelodysplastic syndromes (MDS), myeloproliferative neoplasms, and acute myeloid leukemia. Hallmarks of these diseases have been the emergence of unique genomic signatures and discouraging responses to available therapies. Here, we will critically examine the current options for management and review the rapidly developing opportunities based on advances in CMML and JMML disease biology. Few clinical trials have exclusively been done in CMML, and in JMML, the rarity of the disease limits wide scale participation. Recent case series in JMML suggest that hypomethylating agents (HMAs) are a viable option for bridging to curative intent with allogeneic hematopoietic stem cell transplant or as posttransplant maintenance. Emerging evidence has demonstrated targeting the RAS-pathway via MEK inhibition may also be considered. In CMML, treatment with HMAs is largely derived from data inclusive of MDS patients, including a small number of patients with dysplastic CMML variants. Based on CMML disease biology, additional therapeutic targets being investigated include inhibitors of splicing, CD123/dendritic cell axis, inherent GM-CSF progenitor cell hypersensitivity, and targeting the JAK/STAT pathway. Current evidence is also expanding for oral HMAs. The management of CMML and JMML is rapidly evolving and clinicians must be aware of the genetic landscape and expanding treatment options to ensure these rare populations are afforded therapeutic interventions best suited to their needs.