How does the type of prior treatment affect the risk of therapy-related myeloid neoplasms?

During the American Society of Clinical Oncology (ASCO) Annual Meeting, Alexander Maurer from the AML Hub hosted a group discussion with Michael Ozga and Caner Saygin, both from The Ohio State University, Columbus, US and Abhay Singh from Roswell Park Comprehensive Cancer Center, Buffalo, US. This podcast discusses how the type of prior treatment can affect the risk of therapy-related myeloid neoplasms.

The group start by discussing the problems clinicians face when deciding treatment plans for patients with secondary myeloid neoplasms and describe how exposure to prior DNA damaging agents, cytotoxic therapies, and genotoxic therapies, can lead to a complex karyotype in these patients.

The group then discuss the role of clonal hematopoiesis in the evolution of secondary myeloid neoplasms. Dr Saygin describes how this could be a possibility especially for TP53 mutated, therapy-related AML, he also provides another hypothesis that genotoxic agents could cause de novo mutations. The group also discuss other driving mutations for clonal hematopoiesis including MPN1, SRSF2, and ASXL1, before moving on to discuss how specific genotoxic therapies can generate specific mutations. Dr Saygin and Dr Ozga describe their study in which they analyzed the molecular footprint of patients who had received various genotoxic and cytotoxic agents in order to answer this. Dr Singh also discusses his data on how the development of novel agents, such as immunotherapies may actually reduce the risk of secondary myeloid neoplasms compared to previous treatment options.

The discussion ends on the note that these types of studies will eventuality allow clinicians to predict disease risk better and provide more suitable therapies based on the patient's particular molecular profile.