Emerging Treatments Show Promise in Myelofibrosis

Alice Mims, MD, provides updates on the field of myeloproliferative neoplasms, with a focus on myelofibrosis.

The landscape of myelofibrosis includes a firmly established JAK 1/2 inhibitor with ruxolitinib (Jakafi); however, novel agents such as momelotinib and pacritinib are gaining interest.

The phase III SIMPLIFY-2 trial missed its primary endpoint of superiority with momelotinib in patients with myelofibrosis who had a reduction in spleen volume at 24 weeks for momelotinib versus best alternative therapy at 6.7% versus 5.8%, respectively (95% CI, -8.9% to 10.2%; P = .90).1

However, momelotinib met its secondary endpoint of response rate in total symptom score (TSS), as well as an endpoint related to anemia.

In the phase III SIMPLIFY-1 trial, momelotinib did achieve the primary endpoint of noninferiority versus ruxolitinib when measuring the percentage of patients with myelofibrosis who had at least a 35% reduction in spleen volume at 24 weeks at 26.5% versus 29%, respectively (95% CI, -11.2% to 5.6%; P = .011). Noninferiority for momelotinib was not demonstrated for the important secondary endpoint of response rate in TSS at week 24.2

“Momelotinib did not show superiority, but there was an improvement in anemia compared with ruxolitinib,” said Alice Mims, MD. “In my opinion, there is a role for momelotinib in the future for these patients.”

OncLive: Please provide an overview of your presentation.

In an interview at the 2017 OncLive® State of the Science SummitTM on Hematologic Malignancies, Mims, a medical oncologist at The Ohio State University Comprehensive Cancer Center, provided updates on the field of myeloproliferative neoplasms, with a focus on myelofibrosis.Mims: We discussed myelofibrosis and how there are very limited treatments other than symptomatic therapies. The most exciting therapy has been ruxolitinib, which is a JAK 1/2 inhibitor that has been shown to improve symptomatic splenomegaly as well as constitutional symptoms. However, ruxolitinib can have side effects that cause progressive anemia and it cannot be given in patients with thrombocytopenia.

What are the biggest challenges that remain with ruxolitinib?

What data have we seen with momelotinib and pacritinib?

We are excited because there are newer JAK inhibitors that are being investigated in clinical trials that have also reduced spleen size, as well as improve anemia. These are agents such as momelotinib and pacritinib. One of the biggest questions is the overall survival (OS) that we discussed at this meeting. There has been a report of the 5-year follow-up that discusses what the OS benefit might be with ruxolitinib versus the best available therapy or placebo. The clinical trial design with the allowance of crossover has a lot of confounding data, making it difficult to say if that is a true entity or not. That is one of the big questions about survival data. For momelotinib, there were the SIMPLIFY studies. The SIMPLIFY-1 study looked to see if ruxolitinib was noninferior in patients, and it did demonstrate that it was noninferior in the reduction of splenic size.

The SIMPLIFY-2 study investigated the superiority of momelotinib compared with ruxolitinib. Momelotinib did not show superiority; however, there was an improvement in anemia compared with ruxolitinib. In my opinion, there is a role for momelotinib in the future for these patients.

What are the big remaining challenges for patients with myelofibrosis?

Are there any known risk factors for developing myelofibrosis?

What is the main takeaway from your talk for community oncologists?

Regarding pacritinib, there are still some unanswered questions. Pacritinib was put on hold by the FDA due to concerns for cardiac toxicity and mortality, but this was recently lifted in patients with myelofibrosis. It is being reassessed at different dosing levels. It also has improvement of anemia, so there may be a role for pacritinib based on the outcomes of that data. One challenge is there is not curative therapy other than allogenic transplant. However, the majority of patients are not going to be candidates. Also, therapy has been shown to reverse fibrosis itself, which creates the question of whether there are any therapies that might be able to do that for patients.The only known risk factor for myelofibrosis is if a patient has another myeloid malignancy, specifically a myeloproliferative disorder, such as polycythemia vera or central thrombocytopenia. About 10% to 20% of patients with myelofibrosis will have those proceeding their diagnosis. The main takeaway would be attempting to treat patients based off of symptoms. Anemia is going to be managed better with erythropoietin-stimulating agents if they are candidates for androgen therapy versus immuno-modulating agents. However, splenomegaly and constitutional symptoms have a bigger role for ruxolitinib, [which] does not help patients who have anemia or can even make anemia worse.


  1. Gilead announces top-line results from two phase 3 studies evaluating momelotinib for patients with myelofibrosis. www.gilead.com/news/press-releases/2016/11/gilead-announces-topline-results-from-two-phase-3-studies-evaluating-momelotinib-for-patients-with-myelofibrosis. Updated November 16, 2016. Accessed October 11, 2017.
  2. Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in janus kinase inhibitor—naïve patients with myelofibrosis [published online ahead of print September 20, 2017]. J Clin Oncol. 2017. doi: 10.1200/JCO.2017.73.4418.