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NPM1‐Mutant AML and COVID-19: Modified Protocols for Monitoring Treatment Response

By: Sarah Campen, PharmD
Posted: Monday, September 14, 2020

Chemotherapy protocols for patients with acute myeloid leukemia (AML) with nucleophosmin‐1 (NPM1) mutations have been modified in some patients to a less myelosuppressive regimen—venetoclax and azacitidine—than standard induction chemotherapy with daunorubicin and cytarabine, due to the predicted risk of severe COVID-19 infection in immunocompromised patients. However, modifications to treatment regimens have proved challenging because optimal time points for measuring minimal residual disease have not yet been established for the new regimens, according to an article published in the British Journal of Haematology.

“The impact of persistent bone marrow NPM1 minimal residual disease levels after cycle 2 of venetoclax and azacitidine needs to be reassessed in this new treatment regimen and whether treatment escalation needs to occur at a different time point to that of standard intensive treatment regimens,” explained Panagiotis D. Kottaridis, MD, PhD, of the University College Hospitals NHS Foundation Trust, London, and colleagues.

The authors described the course of treatment of a 40-year-old man with NPM1 type A mutation–positive AML who presented to the hospital in February 2020. Initially treated with daunorubicin, cytarabine, and gemtuzumab ozogamicin, he was treated with a combination of venetoclax and azacitidine for cycles 2 and 3 following admission to the intensive care unit due to a difficult course of hemophagocytic lymphohistiocytosis and concerns over the rapid spread of COVID-19 infection.

He was in complete morphologic remission after cycle 2, with NPM1 mutation levels in the bone marrow; however, after cycle 3, the bone marrow NPM1 minimal residual disease level was positive and higher than after cycle 2. “There is no evidence yet to extrapolate these decision time points to patients being treated with the reduced intensity protocols with venetoclax and azacitidine,” concluded the authors.

Disclosure: The authors reported no conflicts of interest.



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