Previous studies show low- to intermediate-risk acute promyelocytic leukemia (APL) responds favorably to frontline all-trans retinoic acid (ATRA) combined with arsenic trioxide (ATO) over the standard ATRA plus chemotherapy (CHT) regimen.1
The first results of the phase III, open-label, randomized APOLLO trial, presented at the European Hematology Association 2024 Congress, showed that the ATRA-ATO regimen demonstrated superior event-free survival (EFS) over the ATRA-CHT regimen in patients with high-risk (HR) APL as well.2
“These are first results. This is an academic trial, and of course, monitoring has been done for the primary endpoint for the majority of patients, but we’re still doing data cleaning. [Still], I would say this regimen should be the new standard of care in patients with HR APL,” said corresponding author Uwe Platzbecker, MD, of University Hospital Leipzig in Germany.
The trial included 131 evaluable patients ages 18 to 65 years old (median age = 46) at 143 sites in six European countries with newly diagnosed HR APL. Patients were randomized to receive two initial doses of idarubicin (IDA) on days one and three in conjunction with ATO (0.15 mg/kg) + ATRA (45 mg/m2) daily in the ATRA-ATO arm (n=68) until complete response (CR) or ATRA plus idarubicin induction followed by three cycles of CHT-based consolidation in the ATRA-CHT arm (n=63). The primary endpoint was EFS at two years, and secondary endpoints were overall survival (OS), toxicity, measurable residual disease (MRD), and quality of life.
After a median follow-up of 31 months, 91.6% (n=120) of patients were evaluable for disease status. No statistically significant differences were observed in CR or CRi rates (93% vs. 91%; p=0.65), early death rates (7% vs. 10%), or OS (93% vs. 87%; p=0.33) between the ATRA-ATO and ATRA-CHT arms, respectively.
Moreover, no significant difference was observed in differentiation syndrome (1.5% vs. 4.8%; p=0.27) between the ATRA-ATO and the ATRA-CHT arms, respectively. “This is a little less than what you would expect from the literature, and it is attributable to the fact that the data monitoring is still ongoing. We expect that the number may increase a little because of data cleaning, but I can say that differentiation syndrome did not contribute to significant differences in early death between the two arms,” Dr. Platzbecker said.
Nevertheless, the trial met the primary endpoint with significant difference in two-year EFS (88% vs. 70%; p=0.02). Additionally, the cumulative incidence of relapse (CIR) rate was significantly higher in the ATRA-CHT arm (14%) than in the ATRA-ATO arm (1.6%; p=0.011).
The superior CIR “confirms the high and better antileukemic efficacy of this new regimen, and patients in the [ATRA-CHT] arm [who experienced events] could be safely salvaged with the ATRA-ATO-based regimen” Dr. Platzbecker said. “The study sets up a new treatment paradigm in a rare subset of AML.”
Researchers cited early termination of the trial in August 2022 because of slow accrual during the COVID-19 pandemic as a limitation to their trial.
Any conflicts of interest declared by the authors can be found in the original abstract.
References
- Lo-Coco F, Avvisati G, Vignetti M, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111-121.
- Platzbecker U, Adès L, Montesinos P, et al. First results of the APOLLO trial: a randomized phase III study to compare ATO combined with ATRA versus standard AIDA regimen for patients with newly diagnosed, high-risk acute promyelocytic leukemia. Abstract S102. Presented at the European Hematology Association (EHA) 2024 Congress; June 15, 2024; Madrid, Spain.