Real Life Experience with ATRA-Arsenic Trioxide Based Regimen in Acute Promyelocytic Leukemia - Updated Results of the Prospective German Intergroup Napoleon Registry
Authors: Platzbecker Uwe , Lengfelder Eva , Goetze Katharina S , Röllig Christoph , Kramer Michael , Sauer Michaela , Albers Nadine , Heuser Michael , Link Hartmut , Schäfer-Eckart Kerstin , Martin Sonja , Krause Stefan W. , Hänel Mathias , Bochtler Tilmann , Jakob Andreas , Reichle Albrecht , Biersack Harald , Baldus Claudia D. , Goerner Martin , Basara Nadezda , Mezger Joerg , Naumann Ralph , Kuerschner Dorit , de Wit Maike , Nolte Florian , Ringhoffer Mark , Tischler Hans-Joachim , Greiner Jochen , Kremers Stephan , Machherndl-Spandl Sigrid , Koller Elisabeth , Wattad Mohammad Amen , Aschauer Gregor , Radsak Markus , Kubin Thomas , Salih Helmut , Heits Frank , Wolf Dominik , Thiede Christian , Serve Hubert , Duehrsen Ulrich , Hochhaus Andreas , Brümmendorf Tim H. , Bornhäuser Martin , Döhner Hartmut , Ehninger Gerhard , Schlenk Richard F. 
Published: October 2019

Abstract
Background: Standard therapy of acute promyelocytic leukemia has long relied on the combination of All-trans-retinoic acid (ATRA) and chemotherapy. The introduction of arsenic trioxide (ATO) in APL treatment has allowed achievement of similarly high remission and survival rates coupled with significantly reduced myelosuppression. Recent results of the APL0406 trial by the GIMEMA-AMLSG-SAL study groups showed that the combination of ATRA and arsenic trioxide (ATO) is superior to standard ATRA and chemotherapy (CHT) in front-line therapy of low/intermediate risk acute promyelocytic leukemia (APL). The implications of these results for the clinical practice of APL patients in Germany have been uncertain given the fact that ATO is not formally licensed for front-line therapy of APL.
Aim:In order to provide evidence and a reflection of the clinical reality of APL patient care in Germany an intergroup APL registry (National acute promyelocytic leukemia (APL) observational study, NAPOLEON) was recently initiated by several AML study groups.
Methods:Eligible patients are adults at least 18 years of age with newly diagnosed or relapsed APL not beyond the first year of diagnosis. Here we report the first analysis on the series of patients prospectively enrolled into this registry. The study was conducted in accordance with the Declaration of Helsinki, received IRB approval by all participating centers and was registered at ClinicalTrials.gov (NCT02192619).
Results: As of August 1st 2016, 88 patients have been included into the study with a median age of 57 years (range 22-87). All had newly diagnosed APL (100%) with 66% (n=58) being of low/intermediate risk according to the Sanz score. Out of those patients 76% (n=44) received an ATO-ATRA based induction regimen followed by a median of 4 courses of consolidation (according to the APL 0406 study).Of 41 patients evaluable for response to induction, 40/41 (98%) patients achieved complete remission (CR) with the ATRA-ATO arms. Early death rate within 30 days of therapy was 2% (1/44). After a median follow-up of 12 months, the event-free survival, cumulative incidence of relapse and overall survival at 12 months for these patients were 97%, 0% and 97%, respectively. Therapy was well tolerated and no new safety signals have been obtained.
Conclusion:These real life data from a prospective German registry provide further evidence for the safety and sustained anti-leukemic efficacy of ATRA-ATO in low/intermediate risk APL. These results further support ATRA-ATO as the new standard of care in this clinical setting.
Table Demographic, clinical and laboratory characteristics of the eligible patients. Table. Demographic, clinical and laboratory characteristics of the eligible patients.

Disclosures
Platzbecker: TEVA: Honoraria, Research Funding. Greiner:BMS: Research Funding. Thiede:AgenDix: Employment, Other: Ownership. Hochhaus:BMS: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding.