Frontline ATRA/Arsenic Trioxide Improves Survival in APL


The advantage of treating low- or intermediate-risk APL with ATRA plus arsenic trioxide appears to increase over time, according to results of the APL0406 trial.

The advantage of treating low- or intermediate-risk acute promyelocytic leukemia (APL) with a combination of all-trans-retinoic acid (ATRA) plus arsenic trioxide compared with ATRA plus chemotherapy appears to increase over time, according to the final results of the APL0406 trial published in the Journal of Clinical Oncology.

Initial results of the study showed that ATRA and arsenic trioxide was noninferior to standard ATRA and chemotherapy in the first-line setting. These updated results indicated that ATRA plus arsenic trioxide resulted in a similar complete response rate, but improved event-free survival, cumulative incidence of relapse, and overall survival at 50 months.

“Our results support the use of ATRA/arsenic trioxide in patients with newly diagnosed APL and point to this strategy as the new standard of care for low- or intermediate-risk patients,” wrote researchers led by Uwe Platzbecker, MD, of Universitätsklinikum Carl Gustav Carus der Technischen Universität Dresden, Germany. “Studies exploring the role of ATRA/arsenic trioxide are warranted in other APL subsets including high-risk, pediatric, and elderly patients.”

According to the study, the standard of care for patients with APL, ATRA plus chemotherapy, is associated with frequent severe hematologic toxicities and the development of secondary myeloid neoplasms. Arsenic trioxide has been used as a single-agent treatment for APL, and is approved for use in those patients with relapsed or refractory disease.

In this study, Platzbecker and colleagues explored the use of arsenic trioxide in the first-line setting. The prospective trial enrolled 263 patients aged 18 to 71 with newly diagnosed APL. The patients were randomly assigned to ATRA plus arsenic trioxide or ATRA plus chemotherapy.

The rate of complete response was very high for both the patients assigned to ATRA plus arsenic trioxide (100%) and those assigned to the standard of care (97%).

With a median follow-up of 40.6 months, however, patients assigned to the arsenic trioxide arm had significantly improved rates of event-free survival (97.3% vs 80%; P < .001), cumulative incidence of relapse (1.9% vs 13.9%; P = .0013), and overall survival at 50 months (99.2% vs 92.6%; P = .0073) compared with patients assigned ATRA plus chemotherapy.

“This study shows that, compared with ATRA/chemotherapy, the ATRA/arsenic trioxide combination significantly improved both survival and relapse risk in patients with newly diagnosed, low- or intermediate-risk APL,” the researchers wrote. “Compared with our previous report in which no significant differences in disease-free survival and cumulative incidence of relapse rates were found, we report here that the chemotherapy-free approach based on ATRA/arsenic trioxide resulted in higher antileukemic efficacy.”

Additionally, significantly more patients assigned to chemotherapy experienced the grade 3 or 4 hematologic toxicities of neutropenia and thrombocytopenia lasting more than 15 days (P < .001). Febrile neutropenia was also more common in patients assigned to chemotherapy.

“These data indicate that the advantage of ATRA/arsenic trioxide over ATRA/chemotherapy increases over time and that the inclusion of arsenic trioxide in the treatment of low- or intermediate-risk APL not only reduces mortality and hematologic toxicity, but also results in improved and sustained antileukemic activity,” the researchers wrote.

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