Real-Life Analysis of Dasatinib in Chronic Phase CML Patients Aged > 60 Years Resistant/Intolerant to Imatinib.

Abstract 2211

Poster Board II-188

Dasatinib is a 2^nd generation tyrosine-kinase inhibitor active in CML patients resistant or intolerant to Imatinib; at present there is no data on its toxicity and efficacy in unselected elderly patients. To highlight this issue, 97 patients treated with Dasatinib when aged > 60 years were retrospectively evaluated from 16 Italian Centers on a “real-life” basis, including all patients treated at each Center independently from enrolment or not in controlled clinical trials.There were 52 males and 45 females, median age at Dasatinib start was 69.5 years (IR 65.0 – 73.3), Sokal Risk at diagnosis was low in 26 patients, intermediate in 37, high in 15 and not valuable in 19. Forthy-five patients (46.4%) were primarily resistant, 11 (11.4%) were intolerant and 41 (42.2%) had secondary resistance to Imatinib; all patients were in CP when Dasatinib was started. Median time from diagnosis to Dasatinib treatment was 85.0 months (IR 44.8 – 120.0); 53/97 patients (54.6%) had been pretreated with IFN ± Ara-C before Imatinib, all patients received Imatinib at standard dose (400 mg/day) followed in 50/97 (51.5%) by increased dose (600 – 800 mg/day) with an overall median period of Imatinib treatment of 48.6 months (IR 26.9 – 67.0). In addition, 28/97 patients (28.8%) received other 2^nd line treatment (10 Nilotinib, 14 HU +/- other drugs, 3 Imatinib + HU or IFN and 1 allogeneic transplant) before Dasatinib. Starting dose of Dasatinib was 140 mg/day in 47 patients, 100 mg/day in 44 patients and ≥ 50 mg/day in 6 patients, respectively. After a median period of treatment of 15.6 months (IR 7.6 – 23.0) all patients were evaluable for toxicity; on the whole, grade 3 – 4 hematological and extra-hematological toxicities were reported in 36/97 (37.1%) and 27/97 (27.8%) patients, respectively. A grade 3 – 4 hematological toxicity occurred in 25/47 (53.1%) patients receiving 140 mg as compared to 10/44 (22.7%) patients receiving 100 mg (p<0.01); a grade 3 – 4 extra-haematological toxicity occurred in 16 (34.0%) patients receiving 140 mg as compared to 10/44 (22.7%) patients receiving 100 mg (p=0.09). Pleuro-pericardial effusions of all WHO grades occurred in 30/97 patients (30.9%): according to starting dosage, pleuro-pericardial effusions occurred in 19/47 patients (40.4%) treated with 140 mg and in 11/44 patients (25.0%) treated with 100 mg. Overall, 11/97 patients (7 treated with 140 mg, 3 with 100 mg and 1 with < 100 mg) permanently discontinued Dasatinib due to toxicity; a dose reduction was needed in 56/97 patients [43/47 (91.5%) treated with 140 mg and 12/44 (27.3%) with 100 mg (p<0.001)]. As to response, 91 patients were considered evaluable (≥ 3 months of treatment) and 6 were considered as too early; 11 patients (12.0%) did not have any response (including 6 patients with early Dasatinib discontinuation for toxicity and 1 patient died from unrelated 2^nd neoplasia), 26 (28.6%) achieved Hematological Response only, 54 (59.4%) achieved Cytogenetic Response (CyR) (Major CyR in 10, Complete CyR in 44). Among 44 patients in Complete CyR, 29 (31.8% of all 91 evaluable patients) also achieved Molecular Response (MolR) (Major MolR in 14, Complete MolR in 15). According to starting dosage, CyR was achieved in 26/47 patients (55.3%) treated with 140 mg compared with 27/39 patients (69.2%) treated with 100 mg. The mean Overall Survival and Event-Free Survival of the whole cohort of patients were 44.6 months (CI95% 41.2 - 47.9) and 24.8 months (CI95% 20.4 – 29.2), respectively. Present analysis shows that Dasatinib could have a major role in the treatment of unselected patients aged > 60 years resistant/intolerant to Imatinib; in particular, when employed at the current recommended dose of 100 mg/day, it is very effective and has a favourable safety profile also in heavily pretreated elderly subjects.