The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia

Lucy C Fox, Katherine D Cummins, Ben Costello, David Yeung, Rebecca Cleary, Cecily J. Forsyth, Maciek Tatarczuch, Kate Burbury, Olga Motorna, Jake Shortt, Shaun Fleming, Andrew McQuillan, Anthony P Schwarer, Rosemary Harrup, Amy Holmes, Sumita Ratnasingam, Kah-lok Chan, Wei-hsun Hsu, Asma Ashraf, Faye Putt & 1 others Andrew Grigg

Research output: Contribution to journalArticle

Abstract

Key Points • Prescribing appropri-ately for age and car-diovascular risk is likely to result in minimal per-manent toxicity-related dasatinib cessation. • CML patients on dasatinib with pleural effusion are more likely to have achieved MR4.5 after 6-month therapy than those without effusion. 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 5 .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 5 .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.
LanguageEnglish
Pages802-811
Number of pages10
JournalBlood Advances
Volume1
Issue number13
DOIs
Publication statusPublished - 2017

Cite this

Fox, Lucy C ; Cummins, Katherine D ; Costello, Ben ; Yeung, David ; Cleary, Rebecca ; Forsyth, Cecily J. ; 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. / The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia. In: Blood Advances. 2017 ; Vol. 1, No. 13. pp. 802-811.
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abstract = "Key Points • Prescribing appropri-ately for age and car-diovascular risk is likely to result in minimal per-manent toxicity-related dasatinib cessation. • CML patients on dasatinib with pleural effusion are more likely to have achieved MR4.5 after 6-month therapy than those without effusion. 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 5 .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 5 .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.",
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Fox, LC, Cummins, KD, Costello, B, Yeung, D, Cleary, R, Forsyth, CJ, Tatarczuch, M, Burbury, K, Motorna, O, Shortt, J, Fleming, S, McQuillan, A, Schwarer, AP, Harrup, R, Holmes, A, Ratnasingam, S, Chan, K, Hsu, W, Ashraf, A, Putt, F & Grigg, A 2017, 'The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia', Blood Advances, vol. 1, no. 13, pp. 802-811. https://doi.org/10.1182/bloodadvances.2016003889

The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia. / Fox, Lucy C; Cummins, Katherine D; Costello, Ben; Yeung, David; Cleary, Rebecca; Forsyth, Cecily J.; 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.

In: Blood Advances, Vol. 1, No. 13, 2017, p. 802-811.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia

AU - Fox, Lucy C

AU - Cummins, Katherine D

AU - Costello, Ben

AU - Yeung, David

AU - Cleary, Rebecca

AU - Forsyth, Cecily J.

AU - Tatarczuch, Maciek

AU - Burbury, Kate

AU - Motorna, Olga

AU - Shortt, Jake

AU - Fleming, Shaun

AU - McQuillan, Andrew

AU - Schwarer, Anthony P

AU - Harrup, Rosemary

AU - Holmes, Amy

AU - Ratnasingam, Sumita

AU - Chan, Kah-lok

AU - Hsu, Wei-hsun

AU - Ashraf, Asma

AU - Putt, Faye

AU - Grigg, Andrew

PY - 2017

Y1 - 2017

N2 - Key Points • Prescribing appropri-ately for age and car-diovascular risk is likely to result in minimal per-manent toxicity-related dasatinib cessation. • CML patients on dasatinib with pleural effusion are more likely to have achieved MR4.5 after 6-month therapy than those without effusion. 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 5 .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 5 .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.

AB - Key Points • Prescribing appropri-ately for age and car-diovascular risk is likely to result in minimal per-manent toxicity-related dasatinib cessation. • CML patients on dasatinib with pleural effusion are more likely to have achieved MR4.5 after 6-month therapy than those without effusion. 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 5 .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 5 .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.

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DO - 10.1182/bloodadvances.2016003889

M3 - Article

VL - 1

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EP - 811

JO - Blood Advances

T2 - Blood Advances

JF - Blood Advances

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