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Combining all-trans retinoic acid (ATRA) with arsenic trioxide (ATO) and idarubicin significantly improved event-free survival (EFS) compared with the standard treatment of ATRA and anthracycline-based chemotherapy in patients with newly diagnosed, high-risk acute promyelocytic leukemia (APL), the phase III APOLLO trial showed.

The 2-year EFS rate was 88% with ATRA combined with ATO and idarubicin compared with 70% with ATRA-chemotherapy (P=0.02), meeting APOLLO's primary endpoint. Five-year EFS rates were 87% versus 55%, respectively (P=0.0034), reported Uwe Platzbecker, MD, of University Hospital Leipzig in Germany, at the European Hematology Association meeting in Madrid.

The 2-year cumulative incidence of relapse was also significantly lower with the study combination compared with ATRA-chemotherapy (1.6% vs 14%, P=0.011).

While 2-year rates of overall survival were higher with the study combination, the difference was not significant: 93% versus 87% in the ATRA-chemotherapy arm (P=0.17). Five-year rates were also not significantly different (93% vs 82%, P=0.17).

"We believe that these first results of a first-line therapy with ATRA-ATO with two initial doses of idarubicin results in superior event-free survival compared to conventional ATRA-chemotherapy in patients with high-risk APL," Platzbecker said. "Further analysis of the APOLLO trial may support the implementation of this regimen as the new standard of care in patients with high-risk disease."

Session moderator Brian Huntly, PhD, of the University of Cambridge in England, asked Platzbecker what he meant by "further analysis" -- more time or a subgroup analysis.

"We wanted to speak in all transparency," Platzbecker replied. "These are first results. This is an academic trial and monitoring has been done for the primary endpoint for the majority of patients. This was meant to be transparent, and we are waiting for final data cleaning and monitoring. But, I think now, I would say yes ... it should be the new standard of care."

APL is a rare and distinct subtype of acute myeloid leukemia, with diagnosed in the U.S. each year.

Platzbecker noted that with the publication of a ATRA plus ATO had become standard of care in the frontline management of low- and intermediate-risk APL. However, patients with high-risk APL are conventionally treated with ATRA plus chemotherapy,

For the open-label, prospective study, patients were enrolled at 143 sites in six European Union countries from 2016 to 2022. Eligible patients had to be newly diagnosed, have a white blood cell count of more than 10 Gpt/L at diagnosis, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 3, a serum total bilirubin level of ≤3.0 mg/dL, and a serum creatinine level of ≤3.0 mg/dL.

Planned enrollment was 280 patients, but Platzbecker noted that this was limited to 133 patients due to the COVID-19 pandemic, and because of the expiration of a provided study drug.

Median age was 46 years, 51.9% were men, median white blood cell count was 35.7 × 10⁹/L, and median ECOG performance status was 1.

At induction, complete response/complete response with incomplete platelet recovery was 93% for patients receiving ATRA combined with ATO and idarubicin versus 90% in the ATRA-chemotherapy group (P=0.654).

Early death rates (in the first 30 days) were also not significantly different (7% vs 10%, respectively, P=0.456), with the majority of those deaths attributed to intracranial bleeding (three and four deaths).

The rate of molecular resistance was 1.7% with the study combination and 5.5% with ATRA-chemotherapy (P=0.268).

The combination of ATRA plus ATO and idarubicin was associated with less hematologic toxicity. For example, grade 1-4 thrombocytopenia persisting for more than 15 days occurred in 15% of patients compared with 22% of patients in the ATRA-chemotherapy arm during induction, Platzbecker reported, and was "basically absent" during consolidation.

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