A new study showed that a reduced dosage of an anthracycline given in combination with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) had similar efficacy to a standard-dose regimen in induction therapy for newly diagnosed acute promyelocytic leukemia (APL). Study results were reported in the journal Hematology.
The study investigators performed a multicenter, retrospective analysis to ascertain outcomes for patients who received different dosages of an anthracycline during induction therapy for newly diagnosed APL with a white blood cell count above 10 x 109/L. All patients received ATO at 0.16 mg/kg, up to 10 mg, intravenously, and ATRA at 25 mg/m2/d, orally, as part of induction therapy.
Patient groups were defined by receipt of the anthracycline agent idarubicin at either a standard dose of 8 to 12 mg/m2/d or at a lower dose of ≤6 mg/m2/d, with 70 patients in each dosage group. In cases involving use of a different anthracycline agent, a conversion was made. Patients in either group received the anthracycline on days 1 through 3 or on days 1, 3, and 5.
The presence of transcripts of PML–RARa, a marker of APL, was analyzed from patients’ bone marrow at various time points and formed the basis for determining molecular complete remission (mCR) or molecular relapse. Disease-free survival (DFS) and overall survival (OS) were also evaluated.
Early mortality, occurring due to any cause either prior to initiating induction or within the first 30 days of induction, was observed at similar rates in both groups; the rates were 5.7% of the low-dose anthracycline group and 10.0% of the standard-dose group (P =.532). The 2-year DFS rates were 94.6% in the low-dose group and 95.1% in the standard-dose group (P =.657). The 2-year OS rates were 92.8% in the low-dose group and 88.2% in the standard-dose group (P =.951). The median follow-up was 42 months.
In 129 patients who had completed induction and were evaluable for response, the rates of mCR were 84.8% in the low-dose group and 79.4% in the standard-dose group (P =.418).
Compared with the low-dose anthracycline group, patients in the standard-dose group experienced longer durations of grade 4 neutropenia and grade 3 to 4 thrombocytopenia (P <.001 each). They also required higher median volumes of red blood cell transfusions (P <.001) and platelet transfusions (P =.037), and they had a higher infection rate than the low-dose group did (P =.042).
The study investigators concluded that while the sample size was small, the study’s results suggest induction therapy with ATO, ATRA, and low-dose anthracycline shows a similar prognosis as standard-dose anthracycline does for this patient population and with less of a risk of treatment complications.
Wu Y, Ke P, Zhou H, et al. Safety and efficacy of different doses of anthracyclines combined with trioxide and all-trans retinoic acid in the treatment of de novo acute promyelocytic leukemia. Hematology. 2021;26(1):271-276. doi:10.1080/16078454.2021.1889159