Frontline Treatment with Dasatinib in Very Elderly Patients (> 75 Years) with Chronic Myeloid Leukemia: Is It Feasible?
Authors: Latagliata Roberto , Stagno Fabio , Annunziata Mario , Trawinska Malgorzata Monika , Iurlo Alessandra , Sgherza Nicola , Fava Carmen , Gozzini Antonella , Luciano Luigiana , Bonifacio Massimiliano , Sorà Federica , Crescenzi Leonetti Sabrina , Crugnola Monica , Gugliotta Gabriele , Galimberti Sara , Orofino Nicola , Mariggiò Elena , Feo Costanzo , Tiribelli Mario , Mauro Endri , Russo Rossi Antonella , Guarini Attilio , Abruzzese Elisabetta , Vigneri Paolo , Rosti Gianantonio , Breccia Massimo 
Published: October 2019

Abstract
Dasatinib (DAS) has been licensed for first line treatment of patients (pts) with Chronic Myeloid Leukemia (CML): however, in the current clinical practice, DAS is often considered too toxic for the treatment of elderly CML patient. In particular, no data are available in very elderly CML pts as to toxicity and efficacy. To address this issue, we evaluated a "real-life" cohort of 39 CML pts in chronic phase aged > 75 years and treated with frontline DAS in 20 Italian Centers from 6/2012 to 10/2017.
Main clinical features at diagnosis are reported in the Table 1. Overall, 23/39 pts (58.9%) had ≥ 2 comorbidities requiring concomitant therapies: according to ECOG scale, performance status at baseline was 0 - 1 in 34 pts (87.2%) and 2 in 5 pts (12.8%). Median interval from diagnosis to DAS therapy was 0.8 months (IQR 0.5 - 1.4). Daily DAS starting dose was 100 mg in 30 pts (76.9%), 80 mg in 1 pts (2.6%) and 50 mg in 8 pts (20.5%), respectively.
All pts were evaluable for toxicity and efficacy; on the whole, grade 3/4 hematological and extra-hematological toxicities were detected in 6 (15.4%) and 11 (28.2%) pts, respectively. DAS therapy was permanently discontinued in 9 pts (23.0%) due to toxicity (3 pts in the first 12-month period of treatment and 6 beyond).
Pleural effusions of all WHO grades occurred in 12 pts (30.7%) after a median period of DAS treatment of 16.3 months (IQR 2.2 - 31.8): in 4 of them pleural effusion occurred during the first 6-month period of treatment.
Overall, 36/39 patients (92.3%) achieved at any time complete cytogenetic response (CCyR), 30/39 (76.9%) major molecular response (MR 3.0) and 16/39 (41.0%) deep molecular response (MR 4.0/4.5). Only 1 patient (2.6%) evolved in a blastic phase after 13 months from DAS initiation.
After a median period of 27.8 months (IQR 19.1 - 37.5), 5 patients died (1 from blastic phase and 4 from unrelated causes): cumulative event-free survival and overall survival at 36 months were 63.2% (95%CI 45.2 - 81.2) and 85.3% (95%CI 73.3 - 97.3), respectively (Figures 1 and 2).
In conclusion, these data indicate that DAS therapy may have a role also in the treatment of patients aged > 75 years, being effective as in younger subjects and having an acceptable safety profile.

Disclosures
Gugliotta: Novartis: Honoraria; Pfizer: Honoraria; Bristol-Myers Squibb: Honoraria; Incyte: Honoraria. Abruzzese:Ariad: Consultancy; BMS: Consultancy; Novartis: Research Funding; Pfizer: Consultancy. Breccia:Pfizer: Honoraria; BMS: Honoraria; Novartis: Honoraria; Incyte: Honoraria.