The Etiology of Pleural Effusions Develping During Dasatinib Therapy in CML Could Be Variable: Need for Awareness and Investigations

Abstract

Abstract 4456Dasatinib is a highly effective oral TKI for CML at various stages of the disease. The most common non-hematologic side-effect is pleural effusion. The exact mechanism of this pathology remains to be fully elicited, although studies report it to be an immunological phenomenon. Current literature shows dasatinib alone to be the cause of such effusions. More recently, pulmonary hypertensions have been reported on dasatinib therapy.However, in our cohort of CML patients receiving dasatinib as a first or second line therapy, other pathologies were documented. Grade 2/3 unilateral pleural effusions were detected in 3 patients. Case 1.A 31 yr old male with CML-CP was on first line dasatinib 100 mg OD and CCyR was documented at 3 months. At 6 month, he was detected to have grade 1/2 bilateral pleural effusion and was managed with drug interruption and oral dexamethasone with no significant reduction of fluid. CBC was normal. Dasatinib was continued. At one year, he lost cytognetic response with emergence of complex karyotype and medullary lymphoid blast crisis was confirmed. Pleural fluid showed lymphoblasts proven by cytology and immunophenotype. He received vincristine and prednisone followed by a change to imatinib. His disease progressed further and died at 2 years from diagnosis. Case 2.A 39 yr old male with molecular relapse and M244V Abl Kd mutation at 8 years since diagnosis and 6.5 yrs on imatinib 400–800 mg daily was offered dasatinib 100 mg OD. After 24 months, he developed grade2 left pleural effusion which responded poorly to drug interruption, therapeutic tapping and prednisone. A few months later he developed constitutional symptoms and CT chest, bronchoscopy/BAL proved to have left lung tuberculosis. Currently, he is responding favorably to anti-tubercular therapy. He was switched back to imatinib and remains in cytogenetic remission. Case 3.A 21 yr old male with cytogenetic non-responder to imatinib 800 mg daily was put on dasatinib 100 mg OD. An MMR was achieved. He developed left pleural effusion after 4 years of dasatinib. Extensive investigation for any specific pathology was not productive. He was put on empiric anti-tubercular therapy with no response. It is being treated as a dasatinib induced effusion. Conclusions.During dasatinib therapy, the causes of pleural effusions could be varied – drug related, extramedullary blast crisis or tubercular. Radiological, cytological and microbiological investigations could be indicated after careful clinical evaluation. Disclosures:Saikia:Bristol -Myers Squibb: Research Funding, Speakers Bureau.