Characteristics and Outcome of Older Patients with Acute Promyelocytic Leukemia Front-Line Treated with or without Arsenic Trioxide - an International Collaborative Study

Abstract Background: Characteristics and outcome of older patients (pts) with acute promyelocytic leukemia (APL) are unclear due to lack of clinical data. Aims: To describe a large series of older APL pts and compare outcome according to treatment strategy. Methods: We retrospectively studied 475 APL pts (median age, 73.8 yrs; range, 70-90.3 yrs), treated between 1990 and 2018 within four study groups/institutions of the US and Europe (Acute Leukemia French Association, n=228; Programa Espanol de Tratamientos en Hematologia, n=211; Study Alliance Leukemia, n=28; Johns Hopkins School of Medicine, Baltimore, n=8). APL was confirmed either by cytogenetics, fluorescence in situ hybridization and/or polymerase chain reaction. For analysis, pts were grouped according to treatment: i) chemotherapy/all-trans retinoic acid (CTX/ATRA, n=260; consisting of daunorubicin/idarubicin and ATRA for induction and different CTXs+ATRA for consolidation), ii) ATO/ATRA±CTX, n=177 (according to Lo-Coco F, et al. NEJM, 2013, n=23 or CTX/ATO/ATRA, n=154), iii) less intensive therapy, n=26 (reduced CTX, n=2 or ATRA only, n=24) and iv) no treatment/unknown, n=12. Results: Median white blood cell (WBC) and platelet counts at diagnosis were 1.5/nl (range, 0.1-242/nl) and 37/nl (range, 2-261/nl), respectively. Two-hundred twenty-nine pts (48%) were female. Cytogenetic analysis was available in 408 pts and 85 (21%) had additional abnormalities. BCR3 was positive in 138 (44%) of 316 available pts. Only 15 (22%) of 69 tested pts were FLT3-ITD positive. One hundred (22%) of 464 pts had a WBC count >10/nl. Median WBC was significantly lower (P Complete remission (CR) after induction therapy was achieved in 75% (194/259) of the CTX/ATRA group, in 93% (162/174) of the ATO/ATRA±CTX group, and in 50% (13/26) of the less intensive group. Two pts of the CTX/ATRA group and one patient after ATRA only were refractory. Early death rates were 24% (n=63) after CTX/ATRA, 7% (n=12) after ATO/ATRA±CTX and 46% (n=12) in the less intensive group. A logistic regression model revealed age above 75 yrs (odds ratio [OR], 0.53; P=0.02) higher WBC (OR, 0.35; P 10/nl) was associated with an inferior RFS in CTX/ATRA (P 10/nl; hazard ratio [HR], 2.36; P 75 yrs (HR, 2.07; P Conclusions: The ATO-based regimen for first line treatment of elderly APL pts was associated with excellent and sustained response rates. Our data demonstrate the important potential of ATO/ATRA in the primary management of older APL pts. Disclosures Fenaux: Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Jazz: Honoraria, Research Funding. Schlenk: Pfizer: Research Funding, Speakers Bureau. Platzbecker: Celgene: Research Funding. Montesinos: Novartis: Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Speakers Bureau.