Nilotinib 800 Mg Daily as Frontline Therapy of Ph + Chronic Myeloid Leukemia: Dose Delivered and Safety Profile for the GIMEMA CML Working Party.
Authors: Rosti Gianantonio , Castagnetti Fausto , Palandri Francesca , Breccia Massimo , Levato Luciano , Gugliotta Gabriele , Capucci Adele , Cedrone Michele , Fava Carmen , Intermesoli Tamara , Cambrin Giovanna Rege , Stagno Fabio , Tiribelli Mario , Amabile Marilina , Luatti Simona , Poerio Angela , Soverini Simona , Testoni Nicoletta , Alimena Giuliana , Pane Fabrizio , Saglio Giuseppe , Baccarani Michele , Martinelli Giovanni 
Published: October 2019

Abstract
Abstract 2205
Poster Board II-182
Nilotinib is an effective and registered treatment of chronic myeloid leukemia (CML) after imatinib failure. Its efficacy as frontline treatment has been explored in phase 2 trials from MDACC and Italian GIMEMA , whose results have been presented recently (Cortes ASH Rosti, EHA). Here we present a detailed analysis of the safety profile of nilotinib 800 mg daily in the CML early chronic phase (ECP) setting. Briefly, 73 ECP patients (median age 51 yrs, range 18-83 yrs, 21/73 – 29% - ≥ 65 yrs at enrolment) received nilotinib at a dose of 400 mg BID. With a median follow-up of 15 months (range 12-24 months), the CCgR rate at 1 yr was 96%, and the major molecular response (MMolR) rate 85%. During the first 365 days, the treatment was interrupted at least once in 38 patients (52%; overall, 86 interruptions), with a median cumulative duration of drug interruption of 19 days (5.2% of 365 days) per patient (range 3-169 days); 35 pts (48%) received the full prescribed dose. The proportion of patients with ≥ 1 interruption decreased during the first and second quarter and second half (37%, 25% and 22% respectively). The mean daily dose was 600-800 mg, 400-599 mg, and less than 400 mg in 74%, 18% and 8% of patients, respectively. Four AEs (≥ grade 2) accounted for the great majority of dose interruptions: bilirubin increase (38%, no gr. 4), skin rash and/or pruritus (37%, no gr. 4), asymptomatic amylase and/or lipase increase (16%, gr. 4: 4%) (no pancreatitis), transaminases increase (19%, no gr. 4). Notably, only 3 events of peripheral edema/fluid retention have been recorded so far (2 gr 1, 1 gr. 2). No pleural or pericardial effusion. Only one pt permanently discontinued nilotinib for recurrent amylase and lipase increase gr. 3-4 after 7 months on nilotinib, without pancreatitis (normal ECO scan and MRI): the pt. is on imatinib 400 mg daily from 12 months, maintaining the CCyR but loosing MMolR on imatinib. The transient hyperglicemia (gr. 2 and 3: 6%) did not lead to any treatment discontinuation. The hematopoietic toxicity (grade 3-4) was negligible: only 5 events (3 neutropenias and 2 thrombocytopenias) in 5 pts (7%) (all within 3 months from treatment start: 431/438 q2weeks scheduled blood counts evaluable). Nilotinib 800 mg daily is feasible, safe and very effective in ECP CML (ClinicalTrials Gov.NCT00481052). ACKNOWLEDGEMENTS: The Italian Association Against Leukemia-lymphoma and myeloma (BolognAIL), The Fondazione del Monte di Bologna e Ravenna, The Italian Ministery of Education (PRIN 2005, No. 20050 63732_003, and PRIN 2007, No 2007F7 AE7B_002), The University of Bologna, The European Union (European LeukemiaNet).

Disclosures:
No relevant conflicts of interest to declare.