Ruben Mesa, MD: Ruxolitinib as a Myelofibrosis Treatment

JUNE 07, 2019
Laura Genn
Ruxolitinib remains an excellent treatment, but it can be bolstered with additional therapies—including immunomodulatory drugs such as thalidomide—particularly with attention to anemia. In an interview with MD Magazine®, Ruben Mesa, MD, director of the Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discussed treating myelofibrosis with ruxolitinib, in combination with other therapies.

Mesa shared both his own findings and others at American Society of Clinical Oncology (ASCO) 2019 Annual Meeting in order to form a complete picture of the state of myelofibrosis treatment options.
 

MD Mag: Aside from myelofibrosis, polycythemia vera, and acute steroid-refractory graft versus-host disease, what other indications could ruxolitinib benefit as a therapy?

Ruben Mesa, MD: Ruxolitinib, as you mention, is now licensed in myelofibrosis, PV, and now in GBH. The additional 1 is undergoing phase 3 testing, which would be for patients with central thrombocythemia that have failed hydroxyurea, and certainly in our current NCCN guidelines is considered one of the backup therapies as well.

The ability to control the platelets, high counts, and improve symptoms, decrease the risk of thrombosis and bleeding—it clearly has an impact on patients with NPN/MDS overlap syndromes.

So there are patients with chronic myelomonocytic leukemia, particularly if they're proliferative or have the JAK2 mutation, as well as other patients that are overlap patients with MDS but who have proliferative features.

How can risks of anemia be managed in patients prescribed to ruxolitinib therapy?

Ruxolitinib, as a JAK2 inhibitor, inhibits the erythropoietin pathway so the development—I wouldn't even view it as a toxicity. It's truly an on-target effect, and in fact, even the dosing of the drug, that half-life of JAK inhibitors, has very much been balanced against that piece.

All of that said, there is clearly a window to be able to walk through that optimizes the benefit of using the therapy while limiting the impact of anemia. First, we have learned that patients do end up compensating over time, so the anemia does tend to be frontloaded with some amount of recovery.

Second, we have learned that there are certainly times that other agents may be used in combination with ruxolitinib if persistent anemia really extends beyond 3-6 months.

If the erythropoietin level is sub-optimal, supplemental erythropoietin sometimes can be beneficial, particularly if they have Ritalin sufficiency. There have been trials that have shown (that I and my colleagues have led) with a combination of the androgen danazol that can be used along with ruxolitinib. It's a fairly inexpensive, non-toxic agent that can be used for that.

There have been studies at this recent ASCO 2019 that have looked at ruxolitinib combined with immunomodulatory drugs such as thalidomide for people in which significant anemia has been part.

See, for the majority of patients, it's manageable with the issue of dosing as well as some patience, but for those that have difficult anemia or let's say were transfusion-dependent when they started ruxolitinib, the combination therapies as well as new clinical trials are of interest with new agents in combination being tested with agents such as luspatercept and others that might impact anemia.

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