HOUSTON - Congestive heart failure rarely occurs among leukemia patients who take imatinib, researchers at The University of Texas M. D. Anderson Cancer Center found after an exhaustive review of the detailed medical histories of 1,276 patients who enrolled in clinical trials for the drug.
Researchers found 22 patients, or 1.7 percent, had symptoms that could have been caused by heart failure. Of those, 18 had previous medical conditions that could also cause heart failure, such as type II diabetes, hypertension, irregular heartbeat or coronary artery disease. Six had congestive heart failure before entering treatment. The results were reported in the Aug. 15 edition of the journal Blood.
"Imatinib remains a safe drug, but monitoring patients and knowing their medical histories are always important," says Jorge Cortes, M.D., senior author of the report and professor in M. D. Anderson's Department of Leukemia. "There is no current need for routine cardiac-specific monitoring of all patients taking imatinib. However, those with significant cardiac history need to be closely monitored. Patients who develop symptoms of heart failure should be evaluated carefully and treated with standard therapy."
Of the 22 patients found to have cardiovascular conditions, 11 were able to continue on imatinib for their leukemia after dose adjustments and management of the heart failure symptoms. The standard of care for treatment includes the use of beta blockers and angiotensin converting enzyme inhibitors or angiotensin receptor blockers, notes study co-author Jean-Bernard Durand, M.D., an assistant professor in M. D. Anderson's Department of Cardiology. Both classes of drugs are approved by the FDA for treatment of heart failure and recommended by the Heart Failure Society of America.
The team also found the incidence of congestive heart failure among patients receiving imatinib to be comparable to the expected incidence in the general population as reported by the Framingham Heart Study, a defining long-term study of cardiovascular disease in the United States.
Imatinib, known by its brand name Gleevec(tm) and developed by Novartis Pharmaceuticals, is approved by the U.S. Food and Drug Administration for the treatment of chronic myelogenous leukemia (CML), Philadelphia-chromosome positive acute lymphoblastic leukemia d(ALL) and gastrointestinal stromal tumor, a rare solid tumor cancer.
Imatinib is a targeted therapy that inhibits two members of a class of enzymes called tyrosine kinases, which transmit growth and survival signals in cells. The drug also blocks a hybrid tyrosine kinase known to cause CML and Philadelphia-positive ALL.
Before the drug was developed, about only about half of CML patients survived for five years after diagnosis. The five-year survival rate of patients taking imatinib is 95 percent.
In a separate paper late last year, a research team led by scientists at the University of Pennsylvania reported that imatinib may be cardiotoxic in mammals. They found stress-induced damage to the mitochondria - the powerhouse organs in cells - in cardiac muscle of mice given the drug. They also implicated inhibition of Abl, one of the tyrosine kinases targeted by imatinib, as the molecular mechanism that causes the damage.
Additionally, 10 patients at M. D. Anderson who developed congestive heart failure after exposure to imatinib were described in the paper. The paper did not assess the frequency of heart failure among patients taking imatinib or the potential risk factors involved.
Durand, who was also a co-author on the earlier paper, says research continues to address how tyrosine kinase inhibition might affect cardiovascular risk. "We continue to work closely with oncologists to identify early biochemical markers which may predict patients at risk and implement medical therapy earlier to increase the success of tyrosine kinase inhibitors in CML patients," Durand says.
Co-authors of the Blood paper with Cortes and Durand are first author Ehab Atallah, M.D., and Hagop Kantarjian, M.D., chair of the Department of Leukemia at M. D. Anderson.
Kantarjian and Cortes have received research funds from Novartis Pharmaceuticals. M. D. Anderson was the lead institution in clinical trials that proved the efficacy of imatinib for CML.
Journal
Blood