Congress abstract

The introduction over the last decades of differentiating agents targeting the specific genetic aberration involved in pathogenesis, such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), has turned acute promyelocytic leukemia (APL) into the most curable acute leukemia with almost 90% long-term survivors. 1However, 5-20% of patients still relapsed after an initial remission. 1Current guidelines of treatment in relapsed APL indicated the use of standard chemotherapy for early relapses after initial ATO-based treatment and, on the contrary, the use of ATO in case of no prior exposure, early relapse (<6 months) to anthracycline-based therapy or late relapse (>6 months) after ATO regimen. 2 In a large series of relapsed patients treated with ATO, the hematological CR rate was 86%, the complete molecular CR was 52%, the estimated early death rate was 7%, and the estimated overall survival (OS) ranged between 50 and 81% at 24 months. 3A meta-analysis compared the effect of ATO as single agent versus ATO plus ATRA, showing an advantage of the combination in terms of CR, and molecular CR, without increasing early death rate. 4 Is still a matter of discussion the best choice as consolidation treatment in patients re-treated with ATO reinduction: a recent study showed an advantage in OS after 5 years of patients who received autologous stem cell transplant (90.3%) compared to ATO-based maintenance (58.6%). 5ATO was combined with bortezomib in a phase II trial with a molecular CR rate of 86%: PML/RARa is cleared by this combination through p62-dependent autophagy pathway. 6 Oral ATO could be also a possible option: at a median follow-up of 94 months, out of 73 relapsed patients, 43 are still in CR2 with a 10-year leukemic free survival (LFS) of 56.8%.7Among other treatments, in the past was reported the effectiveness of gentuzumab ozogamicin (GO): as single re-induction agent a molecular CR rate of 81% was reported. 8 Tamibarotene was also tested in patients relapsed after ATO induction: the ORR was 64%, but unfortunately the relapses were frequently reported with a median OS of only 9.5 months. 9Few cases of relapsed patients were treated with gilteritinib or with venetoclax in combination with chemotherapy. 10,11 In conclusions, ATO is still the best option also for patients with extramedullary localizations.New drugs have been explored but further data are needed to draw final conclusions.