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3021 Real Life Evaluation of Efficacy and Safety of Bosutinib Therapy in Chronic Myeloid Leukemia Patients

Program: Oral and Poster Abstracts
Session: 632. Chronic Myeloid Leukemia: Therapy: Poster II
Hematology Disease Topics & Pathways:
Diseases, CML, Therapies, Myeloid Malignancies
Sunday, December 2, 2018, 6:00 PM-8:00 PM
Hall GH (San Diego Convention Center)

Imma Attolico, MD1*, Roberto Latagliata2*, Massimo Breccia, MD3*, Elisabetta Abruzzese4, Alessandra Iurlo5*, Isabella Capodanno, MD6*, Mario Annunziata7*, Sara Galimberti8*, Mario Tiribelli9*, Bruno Martino, MD10*, Antonella Gozzini11*, Anna Rita Scortechini, MD12*, Chiara Elena, MD13*, Fausto Castagnetti14, Luigia Luciano, MD15, Carmen Fava16, Patrizia Pregno17*, Fabio Stagno, MD, PhD18, Micaela Bergamaschi, MD19*, Gianni Binotto, MD20*, Massimiliano Bonifacio21*, Giovanni Caocci, MD22*, Monica Crugnola, MD23*, Francesco Tarantini1*, Giorgina Specchia, MD1 and Francesco Albano, MD1*

1University of Bari, Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, Bari, Italy
2Department of Biotechnologies and cellular Hematology, Sapienza Università, Rome, Italy
3Division of Cellular Biotechnologies and Hematology, University "Sapienza", Roma, Italy
4Hematology Unit, S. Eugenio Hospital, Roma, Italy
5Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
6Azienda Unità Sanitaria Locale-IRCCS, Hematology Unit, Reggio Emilia, Italy
7Hematology, Ospedale Cardarelli, Napoli, Italy
8Hematology Department, University of Pisa, Pisa, Italy
9Division of Hematology and BMT, Department of Medical Area, University of Udine, Udine, Italy
10Haematology Dept.- Azienda Ospedaliera Bianchi Melacrino Morelli, Reggio Calabria, Italy
11Divisione di Ematologia-Policlinico Careggi di Firenze, Firenze, ITA
12Hematology Unit, A.O.U. Ospedali Riuniti, Ancona, Italy
13Department of Hematology Oncology, Foundation IRCCS Policlinico San Matteo, Pavia, Italy
14Institute of Hematology "L. e A. Seràgnoli", DIMES, University of Bologna, Bologna, Italy
15Hematology - Department of Clinical Medicine and Surgery, Federico II University, Napoli, Italy
16Department of Clinical and Biological Science, University of Turin, Orbassano, Italy
17Hematology Unit, Az Ospedaliero Universitaria Città' della Salute e della Scienza, Torino, Italy
18Chair and Hematology Section, Ferrarotto Hospital, Catania, Italy
19Hematology Clinic, Policlinico San Martino-IST, Genova, Italy
20Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padova, Italy
21Department of Medicine, Section of Haematology, Verona University, Verona, Italy
22Department of Medical Sciences and Public Health, University of Cagliari, "A.Businco" Hospital, Cagliari, Italy
23Department of Medicine and Surgery, University of Parma, Parma, Italy

Introduction: Bosutinib is a Src/Abl tyrosine kinase inhibitor (TKI) currently licensed for patients with Ph+ chronic-phase (CP), accelerated-phase (AP), or blast-phase (BP) Chronic Myeloid Leukemia after failure or intolerance to at least 2 other TKIs. It can also be prescribed, in accordance with label if, after failure of the first TKI therapy, another option does not seem feasible. Previous studies demonstrated a potent activity of second-line bosutinib across a spectrum of BCR-ABL1 mutations and a distinct toxicity profile compared to other TKIs.

Aim: We retrospectively assessed the efficacy and safety of real life Bosutinib administration in 85 patients resistant/refractory or intolerant to other TKIs, referred to 22 Italian Hematological Institutions. The main features at Bosutinib start are reported in the Table.

Results: At Bosutinib start, all patients were in CP. 60 patients (71%) were resistant/refractory, 25 (29%) were intolerant to previous TKIs. BCR-ABL1 kinase mutations were reported in 5/35 evaluable patients (14%); no T315I was reported. The number of previous TKIs was less than 3 in 24/85 patients (28%) and 3 or more in 61 (72%). Comorbidities were present in 63 patients (74%), the most common being arterial hypertension (40), diabetes (14), cardiac disease (10) and chronic obstructive pulmonary disease (6). The most frequent concomitant medications were: antihypertensive in 55% patients, antiplatelets in 26%, antidiabetic in 19%.

The initial dose was 100 mg in 4/85 patients (5%), 200 mg in 24 (28%), 300 mg in 18 (22%), 400 in 8 (9%); 31 patients (36%) started at the full standard dose of 500 mg.

Major Molecular Response (MMR)/Deep Molecular Response (DMR) were achieved by 37/80 (46%) evaluable patients; 43/80 patients (54%) never reached a MMR/DMR at any time. Best responses in these cases were: Complete Hematologic Response (CHR) in 4 patients (9%), Partial Cytogenetic Response (PCyR) in 6 (14%), Complete Cytogenetic Response (CCyR) in 10 (23%). Dose reductions were necessary in 4 patients (5%) due to adverse events (2 cases of diarrhea, 1 transaminase elevation, 1 skin rash).

After a median follow-up of 26 months (range 3-49), 75/85 patients (88%) are alive and 54/75 patients (72%) are still in treatment. Discontinuations were due to: intolerance in 8/75 patients (11%), loss of response in 3/75 (4%), resistance to therapy in 10/75 (13%). Hematological toxicity was observed in 14 patients (16%), any grade, and grade 3-4 in 3 (3%). Extra-hematological toxicity was reported in 41/85 patients (48%), any grade, and grade 3-4 in 14 patients (16%). Causes of death were: acute myocardial infarction (3), cardiac failure (2), acute respiratory distress (2), allogeneic transplant complications (1), cerebral hemorrhage (2).

Conclusions: In our “real life experience” with Bosutinib, we confirm a stable long-term efficacy in heavily pre-treated, mainly elderly patients with intolerance/resistance to other TKIs, who show an initial response to treatment, as reported in clinical trials. Patients show a fast response to the drug (mainly at three months). Hematological and extrahematological toxicities are manageable.

Disclosures: Breccia: BMS: Honoraria; Incyte: Honoraria; Pfizer: Honoraria; Novartis: Honoraria. Abruzzese: Novartis: Consultancy; Ariad: Consultancy; BMS: Consultancy; Pfizer: Consultancy. Castagnetti: Bristol Meyers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Bonifacio: Novartis: Research Funding; Amgen: Consultancy; Pfizer: Consultancy; Incyte: Consultancy; Bristol Myers Squibb: Consultancy.

*signifies non-member of ASH