Jakafi May Not Associate with Long-Term Benefits in Myelofibrosis Subset

Posted on March 17, 2025March 17, 2025 by mpn_admin

March 16, 2025

Author(s): Spencer Feldman

Fact checked by: Alex Biese

Among patients with calreticulin (CALR)-mutated myelofibrosis, real-world data reveal insights into those with splenomegaly and/or symptoms requiring therapy with Janus kinase 2 (JAK2) inhibitors.

The findings suggest that while Jakafi (ruxolitinib) shows some initial benefits, CALR-mutated patients may require more targeted and innovative therapeutic approaches for better long-term outcomes, according to study findings published in Annals of Hematology.

“Overall, despite the initial benefits of [Jakafi], CALR-mutated patients may require more innovative therapeutic interventions to achieve optimal outcomes. This further emphasizes the necessity of exploring alternative or adjunctive therapies tailored specifically for CALR-mutated individuals,” lead study author Dr. Francesca Palandri and colleagues wrote in the study.

Palandri is currently an adjunct professor primarily based in the Department of Experimental, Diagnostic and Specialty Medicine at the Università di Bologna, Bologna, Italy. She is also a junior researcher at Azienda Ospedaliero-Universitaria di Bologna, Institute of Hematology, Bologna, Italy.

Patients with CALR mutations began Jakafi with more severe disease, including higher peripheral blast counts, lower hemoglobin levels and worse marrow fibrosis, and after a longer median time from diagnosis (2.6 versus 0.7 years) compared to patients with JAK2 mutations. At six months, spleen responses were numerically lower in CALR-mutated patients, who also had lower rates of symptom responses (56.1% versus 66.7%, respectively). However, CALR-mutated patients experienced lower rates of high white blood cell counts.

Furthermore, in patients with delayed Jakafi initiation, anemia and reduced starting doses correlated with poorer survival. Managing anemia through interventions like danazol, erythropoiesis-stimulating agents, iron chelation and optimized Jakafi dosing may improve outcomes, according to study authors. The study also highlights the potential benefits of alternative JAK2 inhibitors with lower hematological toxicity.

Jakafi, Pegasys Combination Beneficial in Newly Diagnosed Polycythemia Vera

Posted on November 5, 2024November 5, 2024 by mpn_admin

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.

Patients With Lower-Risk Myelofibrosis May Respond to Jakafi

Posted on September 25, 2024September 25, 2024 by mpn_admin

September 18, 2024

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.