JAK Inhibition in Myelofibrosis Treatment May Cause Aggressive Lymphoma in Small Percentage of Patients

Although JAK inhibitors are a proven effective treatment for patients with myelofibrosis, a type of myeloproliferative neoplasm (MPN), they may come with a severe downside; in particular, a 16-fold increase in the chance of developing a B-cell lymphoma, according to recent research published in the journal Blood.

Researchers examined 626 patients with MPNs who were diagnosed and treated at the Medical University of Vienna between 1997 and 2016. Of these patients, 69 with myelofibrosis were treated with a JAK1/2 inhib­itor for lymphoma development, which included ruxolitinib (Jakafi), gandotinib, fedratinib, or momelotinib.

Four of these patients (5.8%) developed a B-cell lymphoma compared with 2 patients (less than 1%) who were not treated with a JAK inhibitor.

In a similar assessment of 929 patients with MPNs, including 216 mye-lofibrosis cases, 3 (9.7%) of 31 patients treated with JAK1/2 inhibition developed a lymphoma compared with 1 patient (0.54%) in the control group.

The lymphomas that arose in the study included diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma not other-wise specified.

Incyte, the manufacturer of ruxolitinib, offered a statement that in a large study, they found no correlation at all between their drug and aggres­sive lymphoma.

“An extensive review of the ruxolitinib global safety database, which includes nearly 80,000 patient-years, does not reveal an association between ruxolitinib therapy and lymphomas. We are continuing to evaluate the analysis, but would note that the analysis was not adequately controlled and did not account for factors such as prior treatment exposure, time since MPN diagnosis, or the point at which the JAK1/2 inhibitors were initiated in the patients’ disease course.”

To better understand the potential correlation between JAK inhibition and lymphoma, study author Ulrich Jager, MD, head of the Division of Hematology and Haemostaseology at the Medical University of Vienna in Austria, said that prospective evaluation of these data in larger clinical trials is needed. He also suggested that his colleagues in the hematology/ oncology space report when their patients who are treated with JAK inhib­itor therapy go on to develop lymphoma.