OCCURRENCE OF PLEURAL EFFUSIONS DURING DASATINIB TREATMENT IN ELDERLY CML PATIENTS

Pleural effusions are the most common extra-haematological toxicity observed during Dasatinib (DAS) treatment: their occurrence often requires treatment discontinuation and impairs the otherwise high efficacy of the drug. Aims and Methods We revised 125 patients with Chronic Myelogenous Leukemia (CML) in chronic phase treated in 21 Italian Centers, who received DAS when aged >60 years after being resistant/intolerant to Imatinib (IM), in order to find the most important prognostic factors for pleural effusions. Results There were 63 males and 62 females, Sokal risk score at diagnosis was low in 32 patients, intermediate in 49, high in 19 and not evaluable in 23; median age at DAS start was 69.9 years (IR 65.4-74.4), median interval from diagnosis to DAS therapy was 75.8 months (IR 39.1 - 115.9), 57/125 patients (45.6%) had received an IFN-based therapy before IM. As to IM treatment, all but 9 patients had initially received the 400 mg daily standard dosage and 58/125 patients (46.4%) had increased the dosage to 600 - 800 mg/day; on the whole, median period of IM treatment was 46.6 months (IR 21.8 - 61.8). Starting dosage of DAS was 140 mg in 52 patients, 100 mg in 56 patients and <100 mg in the remaining 17 patients. During treatment, 41/125 patients (32.8%) presented a pleural effusion, which was grade 2 in 31 patients and grade 3 - 4 in 10 patients (24.4% of the 41 patients with pleural effusion and 8% of the entire cohort of patients), according to WHO scale; in 11/41 patients (26.8%), there was a concomitant pericardial effusion. In addition, pleural effusion was recurrent in 19/41 patients (46.4%). Median time from DAS initiation to occurrence of 1st pleural effusion was 10.4 months (IR 2.2-18.1). Among 41 patients with pleural effusion, 8 (19.5%) did not require DAS interruption while 33 (80.5%) discontinued the drug; however, DAS was successfully resumed in 28/33 patients (84.8%) after a median period of 20 days (IR 15 - 38) and, overall, only 5 patients (12.1% of the 41 patients with pleural effusion and 4% of the entire cohort of patients) required permanent DAS discontinuation. The predictive role for pleural effusions of several characteristics (sex, age, Sokal risk, smoke attitude, concomitant cardiological or pulmonary diseases, concomitant diuretic treatment, interval from diagnosis to DAS, state of CHR at DAS start, DAS initial dosage) was evaluated in univariate analysis; only presence of concomitant pulmonary disease (P=0.002), initial dose of DAS (140 mg vs. 100 mg, P=0.01) and Sokal risk at diagnosis (high vs. low-intermediate, P=0.043) were significant. There were no differences among patients with or without pleural effusions as concerns response rates and overall survival. Conclusions. Pleural effusions were common in our unselected population of elderly patients but were clinically manageable and did not seem to affect treatment results; however, a complete pulmonary evaluation before treatment could be useful to tailor the treatment with DAS in elderly patients.