Tag Archives: Jakafi

Jakafi, Pegasys Combination Beneficial in Newly Diagnosed Polycythemia Vera

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November 4, 2024

Author(s): Alex Biese

Fact checked by: Spencer Feldman

Among patients with who were newly diagnosed polycythemia vera (PV), treatment with Jakafi (ruxolitinib) and low-dose Pegasys (pegylated interferon alfa-2a) was found to be beneficial, resulting in high rates of hematologic and molecular response, research has shown.

Findings from the two-year end-of-study results of the phase 2 COMBI II clinical trial, published in Blood Advances, showed that the combination treatment was associated with improvements to patients’ cell counts with what researchers described as acceptable toxicity.

Researchers utilized the participation of 25 patients with PV, with a median age of 70 years. According to the study, 14 patients (56% of participants) achieved remission at 24 months, with three (12%) attaining complete remission and 11 (44%) reaching partial remission. Researchers reported what they observed as significant reductions to abdominal discomfort, night sweats, itching and bone pain, while the median JAK2V617F VAF was decreased from 47% to 7% and 60% of patients achieved molecular remission.

One of the 25 patients dropped out of the study within two years, while one patient discontinued both drugs while two patients each discontinued Jakafi and Pegasys and continued stand-alone therapy with the other drug.

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Patients With Lower-Risk Myelofibrosis May Respond to Jakafi

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By Darlene Dobkowski, MA
Fact checked by Ashley Chan

Responses to treatment with Jakafi (ruxolitinib) were more frequent and durable in patients with intermediate-1 risk (low-risk) myelofibrosis, according to findings from a real-world study.

In addition, patients with intermediate-2 (high-risk) myelofibrosis had lower rates of toxicity from Jakafi treatment, as shown in findings from the study published in the journal Cancer.

After six months of treatment with Jakafi, spleen response rates were observed in 26.8% of patients, with symptom response rates in 67.9% of patients with intermediate-1 risk myelofibrosis.

“Splenomegaly (enlarged spleen) and symptoms may be extremely burdensome also in lower-risk patients, with approximately 40% of such patients starting [Jakafi] with a large splenomegaly and a high symptom score,” the study authors wrote. “This finding again supports how the clinical phenotype of [myelofibrosis] should guide the medical therapeutic approach, without being influenced by the prognostic risk category, which, in contrast, is essential instead for the transplant decision.”

Predictors of responses at six months after initiating treatment with Jakafi included no cytopenia (a condition with a lower-than-normal number of blood cells, which can include hemoglobin levels, platelets and white blood cells), no high-molecular-risk mutations and blasts less than 1%. Out of all these factors, high-molecular-risk mutations continued to have a significant association with responses.

According to The Leukemia & Lymphoma Society, blasts are immature blood cells that are a result of mutated stem cells multiplying uncontrollably. They do not mature into healthy blood cells, nor do they function as such. Abnormal blasts, over time, can surpass the bone marrow’s production of normal healthy blood cells.

At the start of the study, 595 of the 1,055 patients (56.2%) with myelofibrosis had intermediate-1 risk according to two different scoring systems used to classify risk (Dynamic International Prognostic Scoring System and Myelofibrosis Score With Constitutional Symptoms – Peripheral Myeloid Immaturity). Both of these scoring systems take into account certain factors like hemoglobin levels, platelet count, spleen size and symptoms.

The spleen was palpable (meaning that it is enlarged and could be felt through the abdominal wall) at the lower edge of the rib cage at less than 5 centimeters in 5.9% of patients, between 5 and 10 centimeters in 47.4% and greater than 10 centimeters in 39.7%. Of note, 54.1% of patients were highly symptomatic.

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

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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.