Individual needs drive second-line myelofibrosis treatment choices

The choice of second-line myelofibrosis treatment for patients who don’t respond well to Jakafi (ruxolitinib) depends on the individual situation, an analysis showed.

Data suggest that patients with anemia who require regular blood transfusions may benefit most from Ojjaara (momelotinib), while those with low platelet counts may be good candidates for Vonjo (pacritinib). And in patients with normal blood cell counts whose main symptom is an enlarged spleen, Inrebic (fedratinib) may be preferable.

The researchers — an international team of scientists with no connection to the companies that make these medications — stressed that the available data have notable limitations, making it difficult to draw definitive conclusions about how the medicines compare. Still, they said their analysis “provides clinically actionable findings on [Inrebic], [Ojjaara] and [Vonjo] in post-[Jakafi]” myelofibrosis.

The study, “Janus kinase inhibitors after ruxolitinib failure in myelofibrosis: A systematic review and pooled analysis of phase 3 efficacy and integrated safety across clinical trials and real-world evidence,” was published in the British Journal of Haematology.

Myelofibrosis is a form of blood cancer that triggers inflammation and scarring in the bone marrow, which interferes with the production of new blood cells. This can lead to myelofibrosis symptoms such as low blood cell counts and an enlarged spleen, as the spleen tries to produce more blood cells to compensate.

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Comparing treatments

A class of medications called Janus kinase inhibitors is the main disease-modifying treatment used to control myelofibrosis. The first to be approved was Jakafi, which is still commonly used as a first-line treatment. But when Jakafi isn’t adequately controlling the disease or is causing intolerable side effects, patients may switch to a second-line treatment.

Three other Janus kinase inhibitors are approved in the U.S. to treat certain adults with myelofibrosis: Ojjaara, Vonjo, and Inrebic. All three have been proven in clinical trials to help control myelofibrosis, but no trials have directly compared them, which may make it hard for doctors and patients to choose which medicine to use.

Aiming to provide some clarity, the scientists compared available data from clinical trials and real-world studies evaluating each of these three second-line treatments. The researchers stressed that this type of analysis has inherent limitations, as it’s hard to make reliable comparisons between clinical trials with different designs and patient populations. For example, Vonjo has been tested more often in patients with very low platelet levels.

The researchers first estimated the number of patients who achieved a 35% reduction in spleen volume after six months of treatment with each therapy. In this analysis, Inrebic showed the best performance at 32.7%, followed by Vonjo at 21.6%. Inrebic was significantly better than Ojjaara, which had a rate of 15.8%.

The researchers then estimated the number of patients who achieved a 25% reduction in spleen volume. In this analysis, both Inrebic and Ojjaara were essentially indistinguishable, with roughly half of the patients meeting that outcome. Based on these data, the researchers concluded that either medication is equally likely to help shrink the spleen, but patients given Inrebic are more likely to experience substantial shrinkage.

The scientists also evaluated how many patients reported a substantial easing of symptoms, as reflected by a 50% or greater reduction in MFSAF Total Symptom Score after six months of treatment. This endpoint was met by about one-third of patients on Inrebic (32.8%) or Vonjo (32.4%), and about one-quarter of patients on Ojjaara (25.3%), with no statistically significant differences.

While Ojjaara was associated with lower rates of severe anemia than the other two medications, rates of discontinuations due to side effects were similar for all three treatments.

The researchers also noted that, in trials, roughly one in three patients given Ojjaara were able to stop needing blood transfusions. Studies of the other two medications didn’t specifically evaluate transfusion dependence, making it impossible to draw comparisons.

Taken together, the findings suggest that Ojjaara is probably the optimal second-line treatment for people with myelofibrosis whose main complaint is anemia, the researchers said. But in patients whose main issue is an enlarged spleen, Inrebic may be the best choice. And since Vonjo has been shown to be effective in patients with very low platelet counts, it may be the best choice for those with low platelet counts.

The researchers stressed that treatment decisions need to take into account individual situations, noting that each medication also has unique safety monitoring requirements. They called for continued study into how each of these treatments can best be deployed to help patients.

“Looking ahead, biomarker-driven patient selection, combination strategies incorporating [other medications], and prospective registries with harmonized end-points are the three priorities most likely to refine current practice,” the scientists wrote.