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Title: The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia.
Austin Authors: Fox, Lucy C;Cummins, Katherine D;Costello, Ben;Yeung, David;Cleary, Rebecca;Forsyth, Cecily;Tatarczuch, Maciek;Burbury, Kate;Motorna, Olga;Shortt, Jake;Fleming, Shaun;McQuillan, Andrew;Schwarer, Anthony P ;Harrup, Rosemary;Holmes, Amy;Ratnasingam, Sumita;Chan, Kah-Lok;Hsu, Wei-Hsun;Ashraf, Asma;Putt, Faye;Grigg, Andrew P
Affiliation: Royal Hobart Hospital, Hobart, Australia
Austin Health, Heidelberg, Victoria, Australia
Epworth Healthcare, Melbourne, Australia
Alfred Hospital, Melbourne, Australia
Baker IDI Heart and Diabetes Institute, Melbourne, Australia
Royal Adelaide Hospital, Adelaide, Australia
Princess Alexandra Hospital, Brisbane, Australia
Gosford Hospital, Gosford, Australia
Peter MacCallum Cancer Centre, Melbourne, Australia
Monash Health, Clayton, Melbourne, Australia
School of Clinical Sciences at Monash Health, Monash University, Clayton, Melbourne, Australia
Hollywood Medical Centre, Perth, Australia
Box Hill Hospital, Melbourne, Australia
Canberra Hospital, Canberra, Australia
Royal Melbourne Hospital, Melbourne, Australia
St Vincent's Hospital, Melbourne, Australia
Royal Prince Alfred Hospital, Sydney, Australia
Calvary Mater Hospital, Newcastle, Australia
Issue Date: 23-May-2017
Date: 2017
Publication information: Blood advances 2017; 1(13): 802-811
Abstract: Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion (P < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced (P = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions (P = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.
DOI: 10.1182/bloodadvances.2016003889
Journal: Blood advances
PubMed URL: 29296724
PubMed URL:
ISSN: 2473-9529
Type: Journal Article
Appears in Collections:Journal articles

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