Contributions
Abstract: PB1961
Type: Publication Only
Background
Imatinib mesylate is a small-molecule TKI that dramatically changed the treatment landscape for patients with CML. Other TKIs have since been developed (e.g. Dasatinib) as second-line agents for intolerance or refractory disease. TKIs are generally well-tolerated with common side effects being nausea, diarrhea, fluid retention, myalgias and rash. TKIs were first implicated in cardiomyocyte toxicity following a report of ten CML patients who developed early congestive heart failure following treatment with Imatinib (Kerkela, 2006). Several in vitro and in vivo studies have since shown that Imatinib and Dasatinib can induce cardiotoxic effects via both on-target and off-target mechanisms, although the incidence in humans remains unclear (Force, 2011; Savi, 2018). There are no studies to date specifically examining myocardial toxicity in humans on long-term TKI treatment.
Aims
To describe a series of patients (pts) on prolonged TKI therapy for CML with documented myocardial toxicity without another identifiable etiology for the cardiac complication.
Methods
A retrospective chart and data base review was performed on pts with CML treated with TKIs by the Leukemia/BMT Program of BC over a 15-year period (2002-2017). Basic demographic data was collected along with date of commencement of TKI, disease status, TKI dose and response, adverse effects, duration of therapy at diagnosis of myocardial toxicity, investigation and management of cardiac complication and outcome. Specific attention was paid to the presence of traditional cardiac risk factors (RFs) and the presence of alternative etiologies for the myocardial toxicity.
Results
Five pts with chronic-phase CML were identified (Sokal score good-risk in 4 pts, intermediate-risk in 1 pt), 3 males and 2 females, with a median age of 52.6 years (yrs) (range 43.3-56.2) at diagnosis. Myocardial toxicity was identified at a median age of 61.9 yrs (range 56.5-71.1) after median total TKI therapy duration of 12.5 yrs (range 3.3-15.3). All pts had exposure to Imatinib for a median total of 12.5 yrs (range 0.5-15.3) and three had exposure to Dasatinib for median 0.5 yrs (range 0.3-2.8). Four pts had evidence of cardiomyopathy with reduced left ventricular ejection fraction, median 35% (range 20% - 45%) by echocardiography, two with associated pericardial effusion. The fifth patient had a left atrial myxoma. RFs for atherosclerotic disease included obesity (2 pts), type II diabetes mellitus (1 pt) and remote (> 25 yrs) smoking (1 pt). Two pts had remote exposure to cardiotoxic agents (Doxorubicin 26 yrs and Cyclophosphamide 15 yrs previously, respectively). Two pts had cardiac angiography and two pts had MIBI scan with no evidence of ischemic heart disease; all pts were assessed by a cardiologist with no other identifiable explanation for the cardiotoxicity aside from chemotherapy exposure. The atrial myxoma pt underwent surgical resection with no cessation of Imatinib while TKI therapy was held in all pts with cardiomyopathy. All pts commenced medical therapy, improved clinically and echocardiographically and were restarted on TKI therapy.
Conclusion
Despite strong mechanistic evidence of cardiomyocyte toxicity of TKIs, clinical reports in humans are rare. We present a series of pts with delayed cardiotoxicity in the form of cardiomyopathy with reduced systolic function and the first reported case of atrial myxoma presumed secondary to prolonged TKI therapy. Early screening of symptomatic individuals for cardiotoxicity from TKI therapy is strongly recommended.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Adverse reaction, Chronic myeloid leukemia, Tyrosine kinase inhibitor
Abstract: PB1961
Type: Publication Only
Background
Imatinib mesylate is a small-molecule TKI that dramatically changed the treatment landscape for patients with CML. Other TKIs have since been developed (e.g. Dasatinib) as second-line agents for intolerance or refractory disease. TKIs are generally well-tolerated with common side effects being nausea, diarrhea, fluid retention, myalgias and rash. TKIs were first implicated in cardiomyocyte toxicity following a report of ten CML patients who developed early congestive heart failure following treatment with Imatinib (Kerkela, 2006). Several in vitro and in vivo studies have since shown that Imatinib and Dasatinib can induce cardiotoxic effects via both on-target and off-target mechanisms, although the incidence in humans remains unclear (Force, 2011; Savi, 2018). There are no studies to date specifically examining myocardial toxicity in humans on long-term TKI treatment.
Aims
To describe a series of patients (pts) on prolonged TKI therapy for CML with documented myocardial toxicity without another identifiable etiology for the cardiac complication.
Methods
A retrospective chart and data base review was performed on pts with CML treated with TKIs by the Leukemia/BMT Program of BC over a 15-year period (2002-2017). Basic demographic data was collected along with date of commencement of TKI, disease status, TKI dose and response, adverse effects, duration of therapy at diagnosis of myocardial toxicity, investigation and management of cardiac complication and outcome. Specific attention was paid to the presence of traditional cardiac risk factors (RFs) and the presence of alternative etiologies for the myocardial toxicity.
Results
Five pts with chronic-phase CML were identified (Sokal score good-risk in 4 pts, intermediate-risk in 1 pt), 3 males and 2 females, with a median age of 52.6 years (yrs) (range 43.3-56.2) at diagnosis. Myocardial toxicity was identified at a median age of 61.9 yrs (range 56.5-71.1) after median total TKI therapy duration of 12.5 yrs (range 3.3-15.3). All pts had exposure to Imatinib for a median total of 12.5 yrs (range 0.5-15.3) and three had exposure to Dasatinib for median 0.5 yrs (range 0.3-2.8). Four pts had evidence of cardiomyopathy with reduced left ventricular ejection fraction, median 35% (range 20% - 45%) by echocardiography, two with associated pericardial effusion. The fifth patient had a left atrial myxoma. RFs for atherosclerotic disease included obesity (2 pts), type II diabetes mellitus (1 pt) and remote (> 25 yrs) smoking (1 pt). Two pts had remote exposure to cardiotoxic agents (Doxorubicin 26 yrs and Cyclophosphamide 15 yrs previously, respectively). Two pts had cardiac angiography and two pts had MIBI scan with no evidence of ischemic heart disease; all pts were assessed by a cardiologist with no other identifiable explanation for the cardiotoxicity aside from chemotherapy exposure. The atrial myxoma pt underwent surgical resection with no cessation of Imatinib while TKI therapy was held in all pts with cardiomyopathy. All pts commenced medical therapy, improved clinically and echocardiographically and were restarted on TKI therapy.
Conclusion
Despite strong mechanistic evidence of cardiomyocyte toxicity of TKIs, clinical reports in humans are rare. We present a series of pts with delayed cardiotoxicity in the form of cardiomyopathy with reduced systolic function and the first reported case of atrial myxoma presumed secondary to prolonged TKI therapy. Early screening of symptomatic individuals for cardiotoxicity from TKI therapy is strongly recommended.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Adverse reaction, Chronic myeloid leukemia, Tyrosine kinase inhibitor