FORT WORTH, Texas — An escalated daunorubicin dose during induction chemotherapy did not improve clinical outcomes among older patients with acute myeloid leukemia, according to study results presented at HOPA Ahead 2019.
The study — which compared outcomes between patients who received 60 mg/m2 vs. 45 mg/ m2 — showed numerically higher rates of complete remission with incomplete blood count recovery and bloodstream infections among those who received the higher dose, but neither difference reached statistical significance.
Standard treatment for patients with newly diagnosed AML consists of 7+3. However, the anthracycline used and the dose administered can vary by institution, as can cytarabine dose.
The traditional standard at Cleveland Clinic for patients aged older than 60 years had been to administer daunorubicin 45 mg/ m2 on days 1 through 3, and cytarabine 100 mg/ m2 on days 1 through 7.
A study published in 2015 a 90-mg/ m2 dose conferred an OS benefit but also increased toxicity compared with 45-mg/ m2 among patients aged 60 to 65 years.
“Our leukemia group that daunorubicin 90 mg/ m2 probably wouldn’t be well-tolerated by our older patients, but in June 2017 they switched to 60 mg/ m2 in hopes of striking a balance between efficacy and toxicity,” Hanjie Mo, PharmD, PGY2 oncology resident at Cleveland Clinic, told HemOnc Today.
Mo and colleagues conducted a retrospective cohort study of 93 patients aged older than 60 years (median age, 67 years; range, 63-71) with AML who underwent 7+3 induction chemotherapy at Cleveland Clinic’s main campus between July 1, 2015, and June 30, 2018.
Forty-seven patients received daunorubicin 45 mg/ m2 and 46 patients received daunorubicin 60 mg/ m2. Baseline characteristics were balanced between groups with the exception of midostaurin use, which was significantly higher in the 60-mg/ m2 group (17.4% vs. 2.1%).
The rate of complete remission at the end of induction chemotherapy served as the primary endpoint. Secondary outcomes included residual disease on day 14, neutropenia duration, complete remission with incomplete count recovery, hospital length of stay, positive blood cultures, inpatient mortality and transfer to the ICU.
Results revealed no significant differences between the lower dose and higher dose with regard to complete mission (55.3% vs. 56.5%), complete remission with incomplete count recovery (10.6% vs. 19.6%), positive marrow on day 14 (40.4% vs. 37%), positive bloodstream infection (31.9% vs. 47.8%), median duration of neutropenia (31 days vs. 26 days), ICU transfer rate (27.7% vs. 32.6%), median length of stay (34 days vs. 31.5 days) and rate of inpatient mortality (12.8% vs. 10.9%).
Mo acknowledged limitations of the study, including its retrospective nature and the fact it was not sufficiently powered to detect a difference in complete remission.
“Long term, we hope to continue enrolling patients and follow up on additional toxicities in the higher-dose group, including cardiotoxicity,” Mo told HemOnc Today. “We will present these findings to our leukemia group. I think a case can be made that, because we didn’t find any differences in complete remission and descriptively we did see more bloodstream infections in the higher-dose group, we could potentially go back to [the 45-mg/m2 daunorubicin dose] for these patients.” – by Mark Leiser
Reference: Mo H, et al. Daunorubicin dose in induction chemotherapy for older patients with acute myeloid leukemia. Presented at: HOPA Ahead 2019; April 3-6, 2019; Fort Worth, Texas.
Disclosures : The authors report no relevant financial disclosures.