Eight patients had a history of an antecedent hematologic disorder; 14 were in their first relapse; and 13 had disease that was refractory to their last treatment. Two had received a prior AHCT; seven had FLT3 internal tandem duplication (ITD) mutations indicative of particularly poor prognosis; and seven had adverse cytogenetics, she said.
They received one cycle of the therapy, which included 8mg/m2 of mitoxantrone, 80 mg/m2 of etoposide, and 1,000 mg/m2 of cytarabine given intravenously on days 1-6, plus ixazomib at doses of 1 mg (27 patients) or 2 mg (3 patients) given orally on days 1, 4, 8, and 11. An additional 18 patients were treated at the maximum tolerated dose (1 mg, as determined in phase 1 of the trial), Dr. Advani said.
The treatment was well tolerated in most patients. Grade 3-5 nonhematologic toxicities occurred in at least 15% of patients and included infection in 74%, febrile neutropenia in 85%, hypotension in 18%, hypoxia in 19%, mucositis in 15%, hypokalemia in 33%, and hypoalbuminemia in 30%, she said. The early mortality rate was 10%.
Of note, prior studies have demonstrated that the number of mutations in DNMT3A, TP53, ASXL1, and NRAS is associated with a worse response to salvage therapy. Of 21 patients in the current study who had available data, 10 patients had at least one of these mutations, and 8 of those 10 patients achieved CR or CRi, Dr. Advani said.