Dasatinib 100 mg once daily minimizes the occurrence of pleural effusion in patients with chronic myeloid leukemia in chronic phase and efficacy is unaffected in patients who develop pleural effusion

Abstract

BACKGROUND Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily). METHODS To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed. RESULTS With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion. CONCLUSIONS Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy.

The Clinical Impact of Low Doses of Dasatinib in Patients with Chronic Myeloid Leukemia

“…27 Cytogenetic response rates to dasatinib were presented as higher in the group of patients with pleural effusion. 26,28 DASISION study has also indicated the similar results. 29 Visani et al demonstrated that dasatinib, even at low doses, induces and maintains responses (cytogenetic, hematologic and molecular) in real-life CML patients who were resistant and/ or intolerant to imatinib treatment.…”

“…[23][24][25] The incidences of my-elosuppression and pleural effusion were significantly lower with dasatinib 100 mg daily compared with dasatinib at 70 mg twice daily. 26 Close monitoring and timely intervention are necessary for patients at risk for developing pleural effusions. One study showed that in patients with CML who are resistant or intolerant to imatinib, lymphocytosis has been reported during dasatinib treatment and has been associated with increased incidence of pleural effusion.…”

Long‐term safety and efficacy of imatinib mesylate (Gleevec®) in elderly patients with chronic phase chronic myelogenous leukemia: Results of the AFR04 study

“…Cardiac comorbidities are also accepted warnings in the use of nilotinib. Moreover, being aged over 65 years is associated with a relative risk of up to 8.2% for developing pleural effusion, a serious limitation for the use of dasatinib in first-line treatment at the recommended 100 mg daily dose [20]. We thus recommend that IM remains the TKI of choice in elderly patients with newly diagnosed CML in the frontline setting.…”

Effective Molecular Monitoring and the Proper Management of Pleural Effusion During the First-Line Dasatinib Administration in CML

“…20 Porkka et al showed a possible correlation between pleural effusion and lymphocytosis ant the achievement of cytogenetic response with dasatinib treatment. 21 In addition, patients with or without pleural effusion showed similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion. 21 Other studies have presented that patients with lymphocytosis during dasatinib treatment achieved favorable response rate 22,23 and in parallel with this case report result.…”