Inrebic May Reduce Spleen Volume in Myelofibrosis

October 31, 2024

Author(s): Alex Biese

Fact checked by: Spencer Feldman

Among patients with myelofibrosis who have been previously treated with Jakafi (ruxolitinib), treatment with Inrebic (fedratinib) was beneficial, particularly regarding spleen volume reduction (SVR) when compared to treatment with otherwise best-available therapy (BAT), researchers have found.

Findings from the phase 3 FREEDOM2 trial were published in The Lancet Hematology.

“In the FREEDOM2 trial, patients with myelofibrosis previously treated with [Jakafi] showed superior SVR and symptom response when treated with [Inrebic] compared with BAT (predominantly [Jakafi]),” researchers concluded in the study. “The safety profile of [Inrebic] was consistent with previous trials, and mitigation measures effectively managed known adverse events. Overall, the results indicate that [Inrebic] is a promising option for second-line JAK inhibitor treatment of myelofibrosis.”

Inrebic, a type of tyrosine kinase inhibitor, works by blocking JAK2 and other proteins — which, as defined by the National Cancer Institute, may help keep abnormal blood cells or cancer cells from growing. It was approved by the Food and Drug Administration for the treatment of patients with myelofibrosis in 2019.

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Fedratinib and Ruxolitinib: Advice for Deciding Which Agent to Give and When

The introduction of fedratinib (Inrebic) to the treatment landscape of myelofibrosis (MF) and the challenges that have arisen over deciding between administering fedratinib or ruxolitinib (Jakafi) means more community oncologists should consult specialists when treating these patients, said Andrew Kuykendall, MD.

Research shows that fedratinib and the earlier JAK inhibitor, ruxolitinib have similar efficacy in patients with MF. However, their toxicity profiles differ, and the potential for encephalopathy with fedratinib is an ongoing concern, resulting in a black box warning on the label. Now that the agent is FDA approved for the treatment of MF, oncologists are left with a decision of which JAK inhibitor to give to which patients and when to prescribe them.

How to continue using ruxolitinib now that fedratinib is available remains an unanswered question, said Kuykendall, assistant member, Moffitt Cancer Center; however, experts in treating myeloproliferative neoplasms (MPNs) can be a helpful resource for other oncologists.

Another resource for treatment decision-making is clinical data from the JAKARTA-2 trial, which studied fedratinib in patients with MF who were previously treated with ruxolitinib. Findings from a re-analysis of the study were presented at the 2019 ASCO Annual Meeting and showed that 46 of the 83 assessable patients achieved a spleen response (55%; 95% CI, 44%-66%), meeting the primary endpoint of the study.

The most common adverse events included diarrhea (n = 60), nausea (n = 54), vomiting (n = 40), constipation (n = 20), and others. Additionally, hematologic abnormalities including, grade 3/4 anemia (n = 96), thrombocytopenia (n = 68), and neutropenia (n = 23) were seen. Eighteen patients (19%) discontinued treatment due to adverse events.

These data suggest that fedratinib may be a second-line option for patients who are resistant or sensitive to ruxolitinib. The management of the gastrointestinal (GI)-related toxicities and checking of thymine levels to prevent encephalopathy, however, are newer management concerns that physicians must be aware of when administering fedratinib to patients with MF and is another point when consulting an MPN specialist may come in handy.

Read Targeted Oncology’s interview with Dr. Kuykendall.