“Real-life” Frontline Dasatinib Treatment in Unselected Elderly Patients with Chronic Myeloid Leukemia
Authors: Latagliata Roberto , Stagno Fabio , Annunziata Mario , Abruzzese Elisabetta , Iurlo Alessandra , Sgherza Nicola , Fava Carmen , Gozzini Antonella , Giglio Gianfranco , Sorà Federica , Leonetti Crescenzi Sabrina , Bocchia Monica , Crugnola Monica , Gugliotta Gabriele , Capodanno Isabella , Galimberti Sara , Feo Costanzo , Porrini Raffaele , Pregno Patrizia , Breccia Massimo , Vigneri Paolo G , Trawinska Malgorzata Monika , Guarini Attilio , Alimena Giuliana 
Published: October 2019

Abstract
Background Dasatinib has been recently licensed for first line treatment of patients with chronic myeloid leukemia (CML). However, very few data are available as to toxicity and efficacy of dasatinib in unselected elderly CML patients.
Aim To address this issue, we revised a “real-life” cohort of 43 CML patients in chronic phase aged > 65 years treated with frontline dasatinib in 19 Italian Centers from 6/2012 to 6/2014 focusing on toxicity and efficacy data.
Methods The main clinical features of the patients at diagnosis were as follows: M/F 20/23 (46.5%/53.5%), median age 75.2 years [interquartile range (IQR) 70.3 – 79.8), median Hb 12.5 g/dl (IQR 11.0 – 13.7), median WBC 57.7 x 109/l (IQR 29.5 – 100.0), median PLTS 466 x 109/l (IQR 249 – 758). According to Sokal risk classification, 3 patients (6.9%) were low risk, 26 (60.4%) intermediate risk, 10 (23.2%) high risk while 4 (9.5%) were not classificable. 20/43 patients (46.5%) had ≥ 2 comorbidities requiring concomitant therapies: according to ECOG scale, performance status at baseline was 0 – 1 in 36 patients (83.7%) and 2 in 7 patients (16.3%).
Results Median interval from diagnosis to dasatinib start was 23 days (IQR 14 – 32). Dasatinib starting dose was 140 mg/day in 1 patient (2.3%), 100 mg/day in 33 patients (76.7%) and < 100 mg/day in 9 patients (21.0%), respectively. After a median period of treatment of 9.7 months (IQR 4.3 – 17.5) all patients were evaluable for toxicity; on the whole, grade 3 – 4 hematological and extra-hematological toxicities were reported in 4 (9.3%) and 6 (13.9%) patients, respectively. Overall, 7 patients (16.2%) permanently discontinued dasatinib due to toxicity (2 patients in the first 3-month period of treatment and 5 beyond that period). Pleural effusions of all WHO grades occurred in 7 patients (16.2%): in 2 of them the pleural effusion occurred during the first 3-month period of treatment. As to treatment efficacy, 6 patients were considered too early to be evaluated (< 3 months of treatment) and 37 were evaluable for cumulative response; on the whole, 33/37 patients (89.1%) achieved complete cytogenetic response (CCyR) and 23/37 (62.1%) also a major molecular response (MMolR). Response to treatment at different time-points is shown on Table.3rd month6th month12th monthNot evaluable: Too early Not performed11651311219190Evaluable323024Discontinuation2 (6.2%)4 (13.3%)6 (25%)Less than CCyR6 (18,7%)2 (6.7%)0CCyR only17 (53.1%)5 (16.6%)4 (16.6%)MMolR7 (21.9%)19 (63.3%)14 (58.4%)
Conclusions Present data shows that dasatinib could have a major role in the treatment of unselected patients aged > 65 years; indeed, dasatinib seems very effective and has a favourable safety profile also in elderly subjects with comorbidities.

Disclosures
Latagliata: Novartis: Consultancy; Bristol Myers Squibb: Consultancy; Celgene: Consultancy; Shire: Consultancy. Gugliotta:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria. Breccia:novartis: Consultancy; BMS: Consultancy; Celgene: Consultancy.