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Patients With Myelofibrosis Treated With JAK1/2 Inhibitors at Increased Risk of Lymphomas

Laura Joszt
Patients with myelofibrosis who were treated with Janus-kinase (JAK) 1/2 inhibitors have an increased risk for developing B-cell lymphoma. However, researchers believe there is a pre-existing B-cell clone that patients can be tested for before treatment.
The use of Janus-kinase (JAK) 1/2 inhibitors in patients with myelofibrosis is associated with an increased risk of the development of aggressive B-cell lymphomas, according to a study published in Blood, the journal of the American Society of Hematology.

JAK1/2 inhibitors are a mainstay treatment for myeloproliferative neoplasms, although they are not a cure. According to the investigators, a co-incidence of B-cell non-Hodgkin lymphomas developing during treatment has been reported.

“…we started noticing sporadic cases of lymphomas developing in patients being treated for myeloproliferative neoplasms and wanted to know if this phenomenon was connected to treatment,” study coauthor Heinz Gisslinger, MD, of the Medical University of Vienna in Austria, explained in a statement.

Researchers in Europe assessed 626 patients in Vienna with myeloproliferative neoplasms (MPN), 69 of whom had myelofibrosis and were treated with JAK1/2 inhibitors. The analysis found that 5.8% of patients with myelofibrosis (4 out of 69) developed B-cell lymphomas compared with 0.36% (2 out of 557) of patients with MPN receiving conventional treatment.

The researchers observed similar results in a cohort of 929 patients in France with 3.51% of patients receiving JAK1/2 inhibitors developing lymphomas compared with 0.23% of conventionally treated patients.

Once treatment with JAK1/2 inhibitors began, the median time to lymphoma diagnosis was 25 months (range 13-15 months).

However, the investigators also found that patients at risk for developing B-cell lymphoma after treatment with JAK1/2 inhibitors can be identified. In a subgroup analysis of just patients with primary myelofibrosis, all 3 patients who were treated with the inhibitors and developed lymphomas had a pre-existing B-cell clone.

“We determined that patients with this pre-existing B-cell clone in their bone marrow are most at risk for developing aggressive lymphoma,” said Ulrich Jäger, MD, of the Medical University of Vienna. “We also know that up to 16% of people with myelofibrosis have immunoglobulin gene rearrangements like this B-cell clone. Therefore, our findings suggest that all patients with myelofibrosis should be tested for such gene rearrangements before prescribing JAK inhibitors to treat their disease.”

Reference

Porpaczy E, Triplot S, Hoelbl-Kovacic A, et al. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy [published online June 14, 2018]. Blood. doi: 10.1182/blood-2017-10-810739.

 
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