Dactinomycin Produces Durable Response in Patient With NPM1-Mutant AML


Key Points

  • Dactinomycin produced an ongoing morphologic and molecular complete remission that had lasted for 14 months at time of reporting.
  • Hematologic complete remission has been achieved in two of six additional patients.

As reported by Falini et al in a letter to The New England Journal of Medicine, dactinomycin treatment resulted in morphologic and molecular complete remission ongoing at 14 months in a patient with NPM1-mutant acute myeloid leukemia (AML).

NPM1-mutated AML may account for one-third of AML in adults. Since NPM1 is crucial for normal nucleolar function, it was hypothesized that the nucleolus of NPM1-mutated AML cells might be vulnerable to drugs such as dactinomycin that induce nucleolar stress response.


The investigators administered dactinomycin to a 60-year-old patient with NPM1-mutated AML without FLT3 internal tandem duplication mutations who had experienced progression after a single cycle of azacitidine; the patient was selected because low left-ventricular ejection fraction prohibited intensive chemotherapy and dactinomycin does not cause cardiac toxicity.

Treatment consisted of 12.5 μg/kg for 5 consecutive days per cycle. Morphologic and immunohistochemical complete remission was observed after two cycles, and the patient received four additional cycles at intervals of 3 to 4 weeks.

Molecular complete remission was observed after the fourth cycle. The patient had an ongoing morphologic and molecular complete remission that was 14 months in duration at the time of reporting.

Adverse Events

Adverse events included febrile neutropenia and grade 4 thrombocytopenia during cycles 1 and 2, grade 2 oral mucositis during cycles 1 to 3, and superficial skin erosions during cycle 2. Cycles 3 to 6 were given in an outpatient setting, with no blood transfusions being required.

The investigators subsequently used dactinomycin to treat six additional patients with refractory/relapsed NPM1-mutated AML, observing hematologic complete remission in six; one was aged 74 years and had no response to prior azacitidine, and the other was aged 72 years and was in relapse after multiple lines of chemotherapy.

The investigators concluded: “Future studies are warranted to investigate dactinomycin in NPM1-mutated AML and other AML genotypes.”

Brunangelo Falini, MD, of University of Perugia, is the corresponding author for the New England Journal of Medicine letter.

The work was supported by the Associazione Italiana per la Ricerca sul Cancro. For full disclosures of the study authors, visit

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