Abstract
Background: A recent report suggested that imatinib is cardiotoxic and can lead to severe left ventricular dysfunction and heart failure.
Study Aim: To evaluate the incidence of congestive heart failure (CHF) in pts receiving imatinib.
Methods: We reviewed all Grade III and IV cardiac or what could be considered cardiac-related adverse events (eg, shortness of breath, dyspnea on exertion, edema, etc) occurring in pts on clinical trials at MDACC involving imatinib.
Results: 1276 pts were enrolled on clinical trials with imatinib from 7/28/1998 to 7/27/2006. After reviewing all reported adverse events, particularly those that could be considered of at least possible cardiac origin, 22 pts (1.8%) were identified as having symptoms that could be attributed to CHF. The median age for these 22 pts was 70 yrs (range, 49 to 83 yrs); 12 were male. Their diagnosis at the time of imatinib was started was chronic myeloid leukemia in chronic phase (11 of 561 pts, 1.96%), accelerated phase (4 of 384 pts, 1.04%), or blast phase (2 of 123 pt, 1.62%), myeloproliferative disorder (4 of 124 pts, 3.2%), acute lymphoblastic leukemia (1 of 74 pts, 1.35%) and none in 10 pts with c-kit positive AML. Twelve pts (55%) had received prior interferon therapy and 3 pts had received anthracyclins. The median time from start of imatinib therapy to a cardiac adverse event was 162 days (2–2045 days). Imatinib dose at the time of AE was 300mg/d in 1 pt, 400mg/d in 8 pts, 600mg/d in 9 pts, and 800mg/d in 5 pts. At the time these events were reported, 8 were considered possibly or probably related to imatinib. Eighteen pts had previous medical conditions predisposing to cardiac disease: CHF (6 pts, 27%), DM (6 pts, 27%), hypertension (10 pts, 45%), coronary artery disease (CAD) (8 pts, 36%), arrhythmia (3 pts, 14%) and cardiomyopathy (1 pt 5%). Fifteen pts had an echocardiogram or MUGA scan at the time of the event, and 9 of them had documented low ejection fractions (<50%); in only 2 of these 9 pts was there an echocardiogram prior to imatinib (LVEF >50% in both). Of the 9 pts with low ejection fractions at the time of the event , 6 had prior cardiac conditions (3 CAD, 2 CHF and 1 cardiomyopathy), one patient’s low EF etiology could not be determined as no further cardiac evaluation was performed because of progressive disease, and one pt was on anagrelide prior to the event. Eleven of the 22 pts continued imatinib therapy with dose adjustments and management for the CHF symptoms with no further complications.
Conclusions: Imatinib therapy as a causal factor of CHF is uncommon and is mainly seen in elderly patients with pre-existing cardiac conditions. Patients with a previous cardiac history should be monitored closely and treated aggressively with diuretics if they develop fluid retention.
How I manage ibrutinib intolerance and complications in patients with chronic lymphocytic leukemia