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STOCKHOLM —Eliminating anthracyclines from the treatment regimen of children and adolescents newly diagnosed with acute promyelocytic leukemia (APL) is feasible and yields excellent positive outcomes in standard-risk and high-risk patients, new data suggest. At the 2026 European Hematology Association Congress, Franco Locatelli presented the final results of the ICC-APL-02 trial, paving the way for a new treatment approach that dispenses with conventional chemotherapy in this pediatric population.

As the expert noted, the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has radically transformed the treatment of APL, paving the way for chemotherapy-free protocols in standard-risk adults.

Evidence from the APL0406 study supporting the efficacy of this chemotherapy-free approach in the adult population was published more than 10 years ago in The New England Journal of Medicine, and since then, numerous studies have assessed its efficacy and safety in the pediatric population. “None of these studies was truly chemotherapy-free,” said Locatelli, who is director of pediatric hematology and oncology at Ospedale Pediatrico Bambino Gesù in Rome. He explained that anthracyclines were always included in these regimens, albeit at low doses. “High-risk patients have invariably received two to four cycles of anthracycline during the initial induction phase,” he added. 

Well-Tolerated, Risk-Stratified Protocol 

The International Consortium for Childhood APL launched the ICC-APL-02 study, building on the experience from the adult population and with the aim of avoiding the adverse effects of anthracyclines (particularly cardiotoxicity). A total of 114 patients (standard-risk, 76; high-risk, 38; median age, 13 years) from five countries (Italy, France, Czech Republic, Netherlands, and Sweden) were enrolled in the study. Most were treated in Italy (71 patients from 20 centers) and France (35 patients from 29 centers). A risk-stratified protocol combined ATRA and ATO, plus gemtuzumab ozogamicin (GO) on day 2 and 4 of induction only in high-risk patients. 

The median duration of the induction phase was 38 days, with temporary interruption (median, 5 days) of the treatment in 38 patients because of transient and reversible toxicities.

The treatment was well tolerated, with no suspected unexpected serious adverse reaction and no permanent treatment withdrawal for intolerance. Common and known toxicities were reported, including pseudotumor cerebri (14 events, two serious adverse events), differentiation syndrome (47 events, seven serious adverse events), headache (four events, two serious adverse events), and QTc interval prolongation (13 events, three serious adverse events). One reported case of myocarditis was suspected to be GO-related. It resolved without sequelae. One patient died of cerebral hemorrhage during the induction phase. 

Efficacy in Standard-Risk and High-Risk Patients 

All patients achieved hematologic complete remission by the end of induction therapy, while molecular complete remission at the end of the third consolidation course was achieved in all evaluated patients except one. Notably, despite considerable variability in minimal residual disease (MRD) levels, lower MRD values were observed in the high-risk group than in the standard-risk group, which probably reflected the effect of GO treatment.

The efficacy outcomes were extremely positive. At 2 years, overall survival and event-free survival in the whole cohort were 99.1% and 96.9%, respectively. At the same time point, overall survival in the standard-risk and high-risk groups was 100% vs 97.4%, respectively, for and event-free survival was 98.1% vs 94.4%. “The study included patients aged 1-17 years (the study eligibility range was 1-18 years), but no differences in outcomes related to age were observed,” Locatelli told Medscape News Europe. “The main challenge was instead the administration of retinoic acid, as it is given orally and therefore requires closer attention to treatment adherence, particularly in younger children.” 

The findings confirmed the safety and efficacy of an ATRA-ATO treatment in standard-risk patients and notably showed an excellent efficacy in high-risk pediatric patients with newly diagnosed APL. This study established the new standard of care for treating pediatric patients with de novo APL, according to Locatelli.

“For the pediatric community, this study is extremely important because it has tackled the two risk categories of APL,” André Baruchel, head of pediatric hematology and immunology at the University Hospital Robert Debré in Paris, told Medscape News Europe. “We now can treat these children in a rather efficacious way and with a short duration, and we can address both forms of the disease,” he added, underlining the practice-changing nature of the results. 

The study was conducted without industry funding. Pfizer provided gemtuzumab ozogamicin free of charge. Franco Locatelli has served on speaker’s bureaus for Miltenyi, Amgen, Novartis, BMS, Gilead, Medac, Sanofi, SOBI, and Vertex and has served on advisory boards for Amgen, Novartis, Sanofi, and Vertex. Baruchel reported no relevant financial relationships. 

Cristina Ferrario is a molecular biologist and former researcher in molecular oncology at three institutes in Milan. She has a master’s degree in communication and health from the University of Milan and a master’s degree in cancer genetics from the University of Pavia. She has worked as a science journalist for more than 20 years.