The patients had a median age of 63 years. Thirty-four had acute myeloid leukemia (AML), and 6 had high-grade myelodysplastic syndrome; 28 had secondary disease. Nineteen had primary refractory disease, 21 had relapsed disease after a median initial CR duration of 12 months, and 7 had prior allogeneic transplant. The median TRM score for all patients was 2.0, indicating a low risk for treatment-related mortality.
“Cytogenetics distribution, based on Medical Research Council criteria, was as expected,” she added.
At the mitoxantrone maximum tolerated dose of 16 mg/m2 per day – which was established during phase 1 in 26 patients in whom higher dose levels (18 mg/m2 per day) led to dose-limiting encephalopathy and cardiogenic shock – the most common grade 3 or greater adverse events included neutropenic fever, infectious complications, and hypoxia during therapy. This was largely attributed to volume overload and infection, Dr. Halpern said.
“Although three patients did have decreased ejection fraction in cycle 2, this was largely in the setting of sepsis, making the etiology difficult to ascribe to the anthracycline versus sepsis physiology,” she noted.
The median times to an absolute neutrophil count of 500/mcL or greater and platelet count of 50,000/mcL or greater were 29 days each, she noted.
A multivariable analysis controlling for baseline prognostic features showed that the mitoxantrone dose of 16 mg/m2 per day was associated with significantly better overall survival, compared with a dose of 10 mg/m2 per day used in a historical cohort according to standard GCLAM dosing (hazard ratio for death, 0.45). Additionally, more of those receiving a dose of 16 mg/m2 per day went on to transplant (52% vs. 37%), she said. The overall response rate was also higher with the 16-mg/m2 dose, but the difference was not statistically significant (odds ratio, 1.87).
“Further, the outcomes appear to be as good or better with GCLAM with mitoxantrone at 16 mg/m2 compared to other salvage regimens used at our institution, including decitabine priming plus mitoxantrone, etoposide, and cytarabine [d/MEC] and G-CSF with clofarabine and high-dose cytarabine [GCLAC],” she said, noting that the examination is currently ongoing in a larger sample.