26 June 2018

Researchers have identified a possible increase in lymphoma risk for people taking Janus kinase inhibitors to treat myelofibrosis.

The team, led by Dr Heinz Gisslinger, of the Medical University of Vienna in Austria, also believe this side-effect could be avoided by prior screening for a pre-existing B-cell clone.

The study has been published in Blood.

Janus kinase inhibitors, JAK inhibitors, are used to treat myelofibrosis by inhibiting the JAK2 gene, which controls blood cell production.

However, Dr Gisslinger says: "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."

The team gathered information on 69 patients treated for myelofibrosis with JAK inhibitors. They found that 5.8% of these patients developed lymphomas. Of 557 patients who did not receive JAK inhibitors, just 0.36% developed lymphomas.

They explain that this equates to a 16-fold increased risk for aggressive B-cell lymphoma in patients receiving JAK inhibitors.

Further examination revealed pre-existing B-cell clones in the bone marrow in three of the four patients who developed lymphoma. It was this clone that later transformed into lymphoma.

Co-author Dr Veronica Sexl said: "By replicating this link between this B-cell clone and aggressive lymphoma, we hope to speed the discovery of an alternative therapy for myelofibrosis. These findings are going to be valuable in clinical care."

Researcher Dr Ulrich Jager added: "We 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."

Source: Porpaczy, E. et al. Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy. Blood 15 June 2018 doi: 10.1182/blood-2017-10-810739

Link:  http://www.bloodjournal.org/content/early/2018/06/14/blood-2017-10-810739


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