TY - JOUR
T1 - Emerging drugs for the treatment of chronic myelomonocytic leukemia
AU - Ramos Perez, Jorge
AU - Montalban-Bravo, Guillermo
N1 - Publisher Copyright:
© 2020 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2020
Y1 - 2020
N2 - Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal hematologic disorder with heterogenous prognosis, but with no curative therapies with exception of allogeneic transplant. Therapeutic options for patients with CMML are limited, and although hypomethylating agents such as azacitidine and decitabine are the standard of care, only 40% of patients achieve a response, and most responses are transient. Over the last 5 years, significant advances have been made in the understanding of the clonal landscape of CMML, some of the mechanisms associated to resistance to HMA, and other key biological processes involved in disease pathogenesis. Areas covered: The current article reviews the most relevant emerging therapies currently undergoing clinical trials for the treatment of previously untreated or relapsed CMML. Expert opinion: The presence of recurrent somatic mutations in CMML represents therapeutic opportunities to utilize specific small molecule inhibitors such as IDH, FLT3, MEK/ERK, PLK1, or splicing inhibitors and modulators. In addition, other novel agents such as immune therapies, BCL2 or MCL1 inhibitors and other monoclonal antibodies could lead to therapeutic advances. Identifying specific patient populations likely to benefit from some of these interventions, and development of optimal combinations will remain the challenge when determining their role in therapy.
AB - Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal hematologic disorder with heterogenous prognosis, but with no curative therapies with exception of allogeneic transplant. Therapeutic options for patients with CMML are limited, and although hypomethylating agents such as azacitidine and decitabine are the standard of care, only 40% of patients achieve a response, and most responses are transient. Over the last 5 years, significant advances have been made in the understanding of the clonal landscape of CMML, some of the mechanisms associated to resistance to HMA, and other key biological processes involved in disease pathogenesis. Areas covered: The current article reviews the most relevant emerging therapies currently undergoing clinical trials for the treatment of previously untreated or relapsed CMML. Expert opinion: The presence of recurrent somatic mutations in CMML represents therapeutic opportunities to utilize specific small molecule inhibitors such as IDH, FLT3, MEK/ERK, PLK1, or splicing inhibitors and modulators. In addition, other novel agents such as immune therapies, BCL2 or MCL1 inhibitors and other monoclonal antibodies could lead to therapeutic advances. Identifying specific patient populations likely to benefit from some of these interventions, and development of optimal combinations will remain the challenge when determining their role in therapy.
KW - CMML
KW - chronic myelomonocytic leukemia
KW - clinical trials
KW - novel therapies
KW - therapies
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U2 - 10.1080/14728214.2020.1854224
DO - 10.1080/14728214.2020.1854224
M3 - Review article
C2 - 33280448
AN - SCOPUS:85097490780
SN - 1472-8214
VL - 25
SP - 515
EP - 529
JO - Expert Opinion on Emerging Drugs
JF - Expert Opinion on Emerging Drugs
IS - 4
ER -