medwireNews: First-line treatment of high-risk acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) significantly improves event-free survival (EFS) relative to standard treatment, suggest trial data.
Uwe Platzbecker, from University Hospital Leipzig in Germany, reported at the EHA2024 Hybrid Congress in Madrid, Spain, that the 2-year EFS rate was 88% for patients who received ATRA–ATO with two initial doses of idarubicin and 70% for those given ATRA plus anthracycline-based chemotherapy (CHT), a significant difference.
The estimated 5-year EFS rate was also significantly higher in the ATRA–ATO than standard therapy group, at 87% versus 55%, and the safety profile was more favorable. Platzbecker therefore believes that ATRA–ATO “should be the new standard of care” for this population.
Outlining the rationale for the APOLLO trial, the presenter said that ATRA–ATO has been the standard frontline option for low- and intermediate-risk APL since the publication of the APL0406 trial in 2013, but the combination has not been evaluated in randomized trials for high-risk APL (defined as a white blood cell count at diagnosis >10 GPt/L).
The phase 3 trial included 133 patients aged 18–65 years (median 46 years) with a new diagnosis of high-risk APL, who were randomly assigned to receive either:
- ATRA–ATO comprising two doses of idarubicin 12 mg/m2 on day 1 and 3, plus ATRA 45 mg/m2 and ATO 0.15 mg/kg daily until complete remission, followed by consolidation consisting of four courses of ATO 5 days each week, on a 4 weeks on, 4 weeks off schedule, in parallel with seven courses of ATRA on a 2 weeks on, 2 weeks off schedule; or
- ATRA–CHT comprising standard ATRA plus idarubicin induction followed by three cycles of CHT-based consolidation as well as maintenance.
Platzbecker explained that the trial was terminated early due to recruitment challenges during the COVID-19 pandemic and the expiration of the study drug, but it still showed a significant benefit in the primary endpoint of EFS.
ATRA–ATO was also associated with numerically higher overall survival rates than ATRA–CHT at the 2- and 5-year marks, at 93% versus 87% and 93% versus 82%, respectively, but the between-group differences were not statistically significant.
The incidence of hematologic toxicity “was much less” in the ATRA–ATO than ATRA–CHT arm, said the investigator. For instance, thrombocytopenia of grade 1–4 lasting more than 15 days occurred in 15% versus 22% of patients during the induction phase and in 0% versus 16–56% during the consolidation phases.
Similarly, neutropenia of grade 3–4 that lasted more than 15 days was observed in 22% of participants given ATRA–ATO and 46% of those given ATRA–CHT in the induction phase, with rates during the consolidation phases of 1% versus 19–52%.
QTc prolongation of grade 3–4 was more common in the ATRA–ATO than ATRA–CHT group, at rates of 4.4% and 0.0%, respectively, but the presenter highlighted that there was no clinical impact of this side effect, and the incidence of other toxicities, such as hepatic adverse events and differentiation syndrome, was comparable.
There was also no significant difference between the study arms with respect to early mortality – the 30-day mortality rates were 7% and 10% in the ATRA–ATO and ATRA–CHT groups, respectively.
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