Sprycel-induced PAH Seen to Persist for Years in Sizable Number of Leukemia Patients in Study

Sprycel-induced PAH Seen to Persist for Years in Sizable Number of Leukemia Patients in Study

A treatment given people with chronic myelogenous leukemia (CML) — Sprycel (dasatinib) — is known to cause pulmonary arterial hypertension (PAH) in some. Now, researchers in France report that PAH may persist in 37 percent of these leukemia patients for years after the therapy is stopped, although discontinuation is of help to most.

A near majority, 43 percent, also continued to exhibit PAH symptoms despite going off Sprycel, the team also reported, and called their study the “first to report long-term clinical and haemodynamic outcomes in a cohort of patients with dasatinib-induced PAH.”

Long-term outcomes of dasatinib-induced pulmonary arterial hypertension: a population-based study,” published in the European Respiratory Journallooked at 21 CML patients with confirmed Sprycel-induced PAH who were identified through the French Pulmonary Hypertension Registry. An FDA warning concerning this risk was issued in 2011.

CML patients in the study were about 52 years old (15 of the 21 were women), and most — 19 patients — had taken the medication for almost two years (median use of 42 months) before being diagnosed with PAH. Eleven required PAH treatment, and PAH was found to be a “persistent” condition in seven of the 19, the study reported. Four patients died during the course of the research — at 8, 12, 39 and 74 months after PAH diagnosis, but only one had “evidence of persistent PAH” and that death was not directly attributed to the disease.

Treatment discontinuation upon PAH diagnosis is essential, the research team stated.

“The 85.7% survival at 5 years in this study is comparable to the 5-year overall survival rates of 80.6–93.8% reported for CML patients treated with first-line dasatinib in clinical trials, suggesting that PAH contributes to morbidity but may not necessarily contribute to an increased risk of death in most patients if PAH is properly diagnosed and dasatinib is discontinued,” the team wrote.

Researchers compared the patients’ medical and hemodynamic (blood flow circulation) data at the study’s start and at a median of two years later (patients were examined from between one and 81 months), and reported overall improvements in most of the CML patients evaluated.

Hemodynamic assessments measured changes in pulmonary arterial pressure, or blood pressure in the lung arteries, and pulmonary vascular resistance, a measure of the force needed to pump blood through lung arteries.  Patients also were tested using the 6-minute walk distance, a measure of exercise capacity, and most showed overall improvement.

Medical assessments categorized the patients according to the New York Heart Association functional classes (degree of limitation of physical activity). Overall, 76% were found to be class III/IV (greater limitation) at the study’s beginning, and 90% had improved to reach class I/II at the end of their follow-up.

Patients treated with PAH medication generally were seen to have poorer hemodynamic profiles at the start, but improved over time.  Long-term follow-up outcomes were similar in both the treated and untreated groups, the researchers said.

Researchers emphasized the importance of close and continuing examination of Sprycel-treated patients with PAH after the treatment is stopped.

“With persistent symptoms and haemodynamic abnormalities in a significant proportion of patients, and the potential for relapse when specific PAH medications are discontinued, ongoing surveillance is necessary by physicians involved in the care of these patients,” they concluded. “Management of dasatinib-induced PAH necessitates permanent discontinuation and PAH medications may be helpful in severe cases.”

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