Lurbinectedin may be a safe and effective treatment option for myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), according to a study published in Hematological Oncology.1

Previous preclinical in vitro and in vivo studies have demonstrated that lurbinectedin, a next-generation minor groove binder (MGB), has good antitumor activity in solid tumors; its efficacy in AML however, is unknown.

For this phase 1 dose-finding study, investigators enrolled 42 patients with relapsed/refractory AML or MDS. Patients were treated with 2 dosing schedules of lurbinectedin 1-hour IV infusions in a 3+3 design.

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Of the 42 patients, 24 received 3.5 mg, 5 mg, 7 mg, or 6 mg on days 1 and 8. Overall, 3 patients experienced dose-limiting toxicities (DLT) including grade 4 rhabdomyolysis, grade 3 hyperbilirubinemia, and grade 3 oral herpes. Due to DLTs and an elevated dropout rate from early disease progression, the dose schedule was switched to 2 mg, 3 mg, 1 mg, or 1.5 mg for 3 consecutive days on days 1 to 3. No DLTs were observed at this schedule.

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Other frequently observed adverse events (AEs) included gastrointestinal AEs, febrile neutropenia/infections, pulmonary AEs, and renal failure. Common laboratory abnormalities included increased creatinine, anemia, neutropenia, and thrombocytopenia.

Thirty-three of 42 (79%) patients had a decrease in blasts in the peripheral blood or bone marrow, and 1 and 2 patients achieved a partial response or a morphologic leukemia-free state, respectively. All participants discontinued treatment prior to study cutoff, primarily due to progressive disease (30 patients; 71%).

Patients with a chromosome 11q21-23 abnormality had significantly greater reductions in bone marrow blast compared with patients who did not.

The authors concluded that “while no sustained remissions were observed, single-agent lurbinectedin was transiently leukemia suppressive for some patients.”


Benton CB, Chien KS, Tefferi A, et al. Safety and tolerability of lurbinectedin (PM01183) in patients with acute myeloid leukemia and myelodysplastic syndrome [published online August 28, 2018]. Hematol Oncol. doi: 10.1002/hon.2557