PB1725 EVOLUTION OF EFFICACY IN APL TREATMENT WITHIN RUSSIAN MULTICENTER TRIALS 1992-2019.
Authors: E. Parovichnikova, V. Troitskaya, G. Galstyan, A. Sokolov, G. Kliasova, M. Drokov, Z. Fidarova, O. Gavrilina, R. Tivikov, V. Dvirnyk, T. Obukhova, V. Savchenko
Journal: HemaSphere (2019)

Background: Acute promyelocytic leukemia from being the most aggressive and pessimistic type of AML became nowadays the most favorable. The Russian Acute Leukemia Study Group has conducted several prospective clinical trials comprising 282 APL patients from 21 Russian hematologic centers within the last 25 years. Aims: Our goal is to demonstrate the long-term results in APL patients treated with 7 + 3 + ATRA, AIDA protocols and Arsenicum trioxide + ATRA (ATO-ATRA) treatment. Methods: Since January 1992 till December 2018 282 patients with APL were included in two AML trial and four APL clinical trials. Before APL trials (1992-1997) APL patients were treated as AML cohort without ATRA and 32 patients were treated with 7+3+VP-16 and 1-year maintenance with 5+2. The first randomized APL trial (1997-2001) included 61 patients who were treated with 3 7+3+ATRA (ARA-C 100 mg/m2 bid 1-7d, Dauno 60 mg/m2 1-3 d, ATRA 45 mg/m2 1-30 days) courses and 1 year maintenance whether with six 7-days ARA-C+6-MP+ ATRA courses or three 7-days ARA-C+6-MP+ ATRA rotating with three courses of 7-days ATRA. The second APL randomized trial (2001-2008) included 114 pts and has compared two types of prolonged 2-years maintenance after the same three 7+3+ ATRA: 1) 5-days ARA-C+6-MP+ ATRA courses 2)5-days ARA-C+6-MP+ ATRA rotating with courses of 7-days ATRA. The third trial including 53 patients (2008-2016) was modified AIDA protocol and was not randomized. The last ongoing trial with ATO+ATRA has recruited 22 patients. Results: The results of APL treatment within AML cohort were extremely poor with 25% of early death rate and 10% of 5-years survival. After the introduction of ATRA and improvement of supportive care measures within the next ATRA trials we increased CR rate up to 90% with persisting 10% of early death rate. CR rate on ATO+ATRA reached 95%. Death in CR decreased from 12% to 0%, Relapse rate – from 21% to 0 during the last 3 years. 5-years overall survival in patients from ATRA incorporating protocols improved from 60% to 89%, and achieved 95% in 3 years by ATO+ATRA (Pic.1, Pic.2). High risk patients (WBC > 10x109/l) in 7+3+ATRA and AIDA cohort did much worse with 40% of 5-years survival vs 70%. There is no differences so far in a small ATO+ATRA group. It was also demonstrated during the first APL trials that centers with much less experience of APL treatment (less than 6 patients included) provided much worse results due to poor transfusiologic support and so higher early death rate (5-years OS - 55% vs 90%). The last two trials are concentrating patients in 2-3 hematological centers possessing more experience.Summary/Conclusion: APL is a curable disease with remaining high risks of deaths during induction. Russian APL clinical trials provided the same as elsewhere improvement in long-term results. APL should be preferentially concentrated and treated in experienced hematologic centers.