Momelotinib May Set New Standard in Myelofibrosis, Expert Says

Momelotinib improved outcomes and helped combat anemia better than danazol (Danocrine) in patients with myelofibrosis previously treated with JAK inhibitors, and could also yield improved transfusion independence, according to Srdan Verstovsek, MD, PhD.¹

Srdan Verstovsek, MD, PhD, a hematologist/oncologist, professor of medicine, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, and chief of the section for myeloproliferative neoplasms in the department of leukemia at the University of Texas MD Anderson Cancer Center

In an interview with CancerNetwork^®, Verstovsek, a hematologist/oncologist, professor of medicine, director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, and chief of the section for myeloproliferative neoplasms in the department of leukemia at the University of Texas MD Anderson Cancer Center, data from the phase 3 MOMENTUM study (NCT04173494) and why momelotinib could be poised to become standard of care in the second-line setting for those with anemia.

“In the [second-line] setting, there was a need for a new drug,” Verstovsek said. “The MOMENTUM study [demonstrated] the benefit of momelotinib. If it gets approved in the summer of 2023, it will become a new standard of care for patients in a second-line setting in the United States.”

Patients treated with danazol (n = 65) reported anemia at a higher rate (75%) than those treated with momelotinib (n = 130; 61%).

A 50% or greater reduction in total symptom score occurred in 32 patients treated with momelotinib compared with6 of those treated with danazol. Roughly 40% of patients had a 25% or greater reduction in spleen volume with momelotinib vs 6% with danazol; reductions of 35% or more occurred in 23% vs 3%, respectively.

CancerNetwork^®: What was the rationale for assessing momelotinib compared with danazol in myelofibrosis and anemia?

When it comes to therapy for myelofibrosis, we face 3 main clinical problems that we [must] counteract in our patients. That includes progressive enlargement in the spleen, symptomatic splenomegaly. Then there are general systemic symptoms like night sweats, nausea, itching, bone aches and pains, cachexia, weight loss, and anemia. We don’t have any drug approved for anemia.

But we use danazol, an anabolic steroid that has been shown in clinical studies to improve [anemia] in some patients, but not in too many, and not for too long. It can also improve quality of life because it’s an anabolic steroid. It’s listed as a potentially useful drug in the management of patients with myelofibrosis.

When it comes to its utility, it’s usually a second-line choice after JAK inhibitors like ruxolitinib, fedratinib [Inrebic], or pacritinib [Vonjo]. These are 3 [FDA] approved JAK inhibitors that usually help with quality of life [and] may help with the spleen, but do not help much with anemia at all. Quite the opposite: they can worsen anemia. Once they don’t work, what do you do? You can use danazol.

That’s the rationale for [assessing] momelotinib, a new type of drug, compared with danazol. It can improve anemia—unlike any other kind of drug—it can improve quality of life, and it can control the spleen. In the second-line setting, you have patients who were failed by frontline JAK inhibitors because of anemia. They don’t feel well, they may still have some issues with the spleen.

What were the standout findings of this research?

The study was in patients who were symptomatic and anemic and may or may not have had a big spleen, for whom the standard practice JAK inhibitor failed The primary end point of the MOMENTUM study was … improved quality of life. In this double-blind trial, momelotinib was much better than danazol, but the anemia benefit is what excites me the most as a clinician taking care of patients with myelofibrosis.

I can tell my patients, ‘Yeah, this is very good for anemia.’ I can [also] tell them they can maintain transfusion independence or become transfusion independent. It’s a big deal not having blood transfusions. “You can feel better,” I tell patients, “You can have improvements in red blood cell count, you may eliminate the need for the blood transfusions, and, by the way, your spleen will be smaller, as well.”

[The trial highlighted] a combination of quality-of-life improvement and an immune response. Transfusion independence is the key to my excitement [with] momelotinib as a drug. I will likely use it in most patients in the second-line setting.

How might the use of momelotinib impact how patients are treated?

The phase 3 MOMENTUM study was in an area of care for our patients with myelofibrosis where we need the most help. [Sometimes] the standard frontline JAK inhibitors, most often ruxolitinib and sometimes pacritinib for patients with low platelet counts, do not work anymore. [When] patients are anemic and symptomatic, you don’t have too many choices. You can use one of the other JAK inhibitors again or one after the other, but they will not improve the anemia much at all, and they may not even work.

Are there any plans for future research or analyses of these data?

Interestingly, there’s a possibility that momelotinib can prolong the life of the patients. Some preliminary results from the MOMENTUM study after longer follow-up were presented a couple months ago, suggesting that patients who are transfusion independent…may live longer than others.² Not too many drugs prolong the life of the patients [in this setting]. We know that ruxolitinib can do that in the frontline setting. [However], in the second-line setting, life expectancy, on average, is around 2 years, maybe shorter. Prolonging life is extra value, for sure.

Also, of course, there may be combinations, [such as] momelotinib with other investigational agents that may enhance the benefits even more.

Was there anything else you wanted to add?

We have now reached the level where we have potentially a fourth drug approved for myelofibrosis. We are good at [managing] the symptoms and the spleen. Now, we can [control] the anemia to a degree but there is room for more.

There are several other drugs in different categories [with] many [different] mechanisms of action that may become very useful in combination with JAK inhibitors to enhance what they do and achieve other benefits. We may even start thinking about doublets or triplets in the future to make myelofibrosis as chronic as clinically possible.

Right now, we still go by the average survival of 5 to 7 years. I hope that within 5 or 10 years, we start talking about an average survival of 15 to 20 years because we will be use the combinations or triplets to control the disease for much longer.

We have a bright future in front of us.

References

1. Verstovsek S, Gerds AT, Vannucchi AM, et al; MOMENTUM Study Investigators. Momelotinib versus danazol in symptomatic patients with anaemia and myelofibrosis (MOMENTUM): results from an international, double-blind, randomised, controlled, phase 3 study. Lancet. 2023;401(10373):269-280. doi:10.1016/S0140-6736(22)02036-0
2. Gerds AT, Mesa RA, Vannucchi AM, et al. Updated results from the Momentum phase 3 study of momelotinib (MMB) versus danazol (DAN) in sympatomatic and anemic myelofibrosis (MF) patients previously treated with a JAK inhibitor. Presented at: 2022 ASH Annual Meeting; December 10-13, 2022; New Orleans, LA. Abstract 627.