Dactinomycin in acute myeloid leukemia with NPM1 mutations.

Abstract

Complete responses have been observed in NPM1-mutated AML patients with dactinomycin, a nucleolar stress-inducing drug. Here, we report a single-center experience of compassionate use of dactinomycin in untreated or relapsed/ refractory NPM1-mutated AML. From September 2015 to February 2019, 26 adult patients with NPM1-mutated AML received dactinomycin in different situations: front-line treatment in 4 unfit patients (16%); morphologic (n=16, 62%), molecular relapses (n=4, 16%), refractory disease (n=1, 13%), or postremission therapy in second complete response (n=1, 13%). Median age was 62.5 years. Median number of dactinomycin cycle was 1 (1-8), and 7 patients (27%) received more than 3 cycles. Three out of 17 patients (18%) in morphologic relapse or refractory to chemotherapy achieved complete remission after the first cycle of dactinomycin. None of the 4 patients unfit for intensive chemotherapy responded to dactinomycin as front-line therapy. Grade 3-4 adverse events were thrombocytopenia (n=11, 42%), neutropenia (n=11, 42%), GI toxicity (n=6, 23%), mucositis (n=5, 19%), lung infection (n=5, 19%), and skin rash (n=2, 7.6%). Dactinomycin is an inexpensive and easily available drug that may induce significant responses in few AML patients with NPM1 mutations with an acceptable safety profile.