Oral blood cancer drug may worsen cardiometabolic health
An oral chemotherapy treatment used to treat myeloproliferative neoplasms is associated with substantial weight gain and increased systolic blood pressure, according to findings from a real-world analysis published in Scientific Reports.
The drug, ruxolitinib (Jakafi, Incyte), was the first and currently remains the most widely used FDA-approved mechanism-based therapy for myeloproliferative neoplasms. Ruxolitinib is a Janus kinases (JAK) 1/2 inhibitor, an enzyme-blocker that affects blood cell production.
“As people are living longer with cancers and remaining on treatment long term, it is increasingly important that we understand the metabolic consequences of novel, targeted cancer therapies,” Emily J. Gallagher, PhD, assistant professor of endocrinology, diabetes and bone disease at the Icahn School of Medicine at Mount Sinai, told Endocrine Today. “In addition, we found increased systolic blood pressure and liver enzymes. Our correlative preclinical studies suggested that these effects may be due to direct inhibition of JAK1/2 signaling in adipose tissue. We found that JAK1/2 inhibition with ruxolitinib in patients with myeloproliferative neoplasms led to significant weight gain in more than half of patients, with many patients unexpectedly developing obesity.”
In a retrospective cohort study, Gallagher and colleagues analyzed data from 69 adults with myeloproliferative neoplasms who started ruxolitinib between 2010 and 2017 at Mount Sinai, identified via electronic medical records (50.7% women; mean age, 65 years; mean baseline BMI, 25.8 kg/m²). Researchers assessed indication for starting ruxolitinib, dates of ruxolitinib initiation and discontinuation, and the duration of follow-up after ruxolitinib initiation, as well as values for baseline and follow-up body weight, height and BMI, diastolic and systolic BP, glucose, complete blood count, HbA1c, lipid profile, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST) and medication history.
The researchers found that body weight increased from a mean of 73.9 kg at baseline to 78.54 kg at 72 weeks (P < .001), with 50% of patients gaining more than 5% of their baseline body weight. BMI increased from 25.8 kg/m² at baseline to 27.5 kg/m² at 72 weeks (P < .001). Compared with baseline measurements, adults treated with ruxolitinib had a higher systolic BP (P = .03), serum AST (P = .01), and ALT (P = .04) at 72 weeks.
“This study is the first step in understanding the metabolic consequences of this class of targeted therapy,” Gallagher said. “It will be important to perform further studies to understand why certain patients gain weight while others do not, and to gain a greater understanding of the mechanisms underlying the weight gain.”
Gallagher said researchers must understand the long-term consequences of the weight gain and how it may affect quality of life and comorbid diseases, and perform studies to determine how best to treat people who experience unwanted weight gain.
“It is important to recognize that we did not study long-term survival, and so at present, we do not know if the weight gain associated with ruxolitinib is associated with changes in long-term survival,” Gallagher said. – by Regina Schaffer
For more information:
Emily J. Gallagher, PhD, can be reached at the Division of Endocrinology, Diabetes and Bone Disease, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029; email: Emily.firstname.lastname@example.org.
Disclosure: Gallagher reports she has served on an advisory board for Novartis.