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Rebecca Olin, MD, MS


Dactinomycin Under Study in Management of Resistant NPM1-Mutated AML

By: Joseph Fanelli
Posted: Wednesday, May 12, 2021

According to investigational findings presented in Leukemia, the chemotherapeutic agent dactinomycin may prove to be a treatment alternative for patients with relapsed or refractory NPM1-mutated acute myeloid leukemia (AML). Brunangelo Falini, MD, of the University of Perugia, Italy, and colleagues found that this older, lower-cost agent was relatively well tolerated among patients.

“Deeper understanding of the mechanisms behind nucleolar stress response and the apparent higher sensitivity of NPM1-mutated cells to dactinomycin will help optimize new therapeutic approaches in this setting,” the authors concluded.

In this phase II pilot study, the authors enrolled 10 patients with NPM1-mutated AML who had hematologic relapse or refractory disease. The patients were treated with 15 µg/kg of dactinomycin daily for 5 days followed by an interval of 2 to 4 weeks. Those patients who achieved a complete response or a complete response with incomplete marrow recovery received an additional induction cycle until progressive disease occurred.
Of the nine patients, four achieved a complete response or a complete response with incomplete marrow recovery after one or two induction cycles. However, three of those patients relapsed within 7 months of treatment. In all cases, hematologic relapse was anticipated by increasing NPM1-mutant transcripts and detection of cytoplasmic NPM1 in blood marrow blasts by immunohistochemistry. One patient who had an allogeneic hematopoietic stem cell transplant is still in molecular complete response for more than 4 years.
The authors observed grade 4 anemia, thrombocytopenia, and neutropenia consistently during induction cycles, most likely because of bone marrow infiltration, they noted. Grade 3 or higher hematologic toxicities were also observed during consolidation cycles but were usually considered to be manageable in outpatient settings. Notably, the authors said, in the four patients who had at least two consolidation cycles, the platelet nadir occurred at a median time of 11 days in both consolidation cycles 1 and 2.

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