Dual SVR/TI Response With Momelotinib Confers OS Benefit in Myelofibrosis With Anemia and Low Platelet Counts

Subgroup analysis data indicating improved prognosis with momelotinib (Ojjaara) over ruxolitinib (Jakafi) after achievement of a dual spleen volume (SVR) and transfusion independence (TI) response at week 24 support the use of momelotinib as the preferred initial JAK inhibitor in JAK inhibitor–naive patients with myelofibrosis who have anemia and low platelet counts, according to Francesca Palandri, MD, PhD.

Findings from the phase 3 SIMPLIFY-1 trial (NCT01969838) supported the 2023 FDA approval of momelotinib for the treatment of adult patients with intermediate- or high-risk myelofibrosis and anemia.1 In this trial, patients who were JAK inhibitor–naive were randomly assigned to receive momelotinib (n = 86) or ruxolitinib (n = 95).2 The rates of SVR of at least 35% (SVR35) were noninferior between the 2 arms, at 31.4% (95% CI, 21.8%-42.3%) with momelotinib vs 32.6% (95% CI, 23.4%-43.0%) with ruxolitinib.

Based on these data, investigators assessed differential clinical outcomes in patients with lower baseline platelet counts, as well as the clinical relevance of achieving dual SVR35 and TI responses at week 24 with momelotinib.3 Findings presented at the 2025 EHA Congress showed that at week 24, the rate of SVR35 and TI in patients with baseline hemoglobin levels lower than 10 g/dL and baseline platelet levels lower than 200 x 109/L was 33% in the momelotinib arm (n = 49) vs 2% in the ruxolitinib arm (n = 47). Additionally, the overall survival (OS) outcomes at week 24 were better in patients from the momelotinib arm who achieved SVR35 plus TI (HR, 0.40; 95% CI, 0.18-0.89) or TI only (HR, 0.19; 95% CI, 0.06-0.65) vs those who achieved SVR35 only (HR, 0.78; 95% CI, 0.18-3.34).

“The rate of dual response was significantly higher with momelotinib in [most] patient subgroups,” Palandri said in an interview with OncLive®.

In the interview, Palandri discussed previously reported outcomes from SIMPLIFY-1 that served as the impetus for this subgroup analysis, key results from the analysis, and how these findings may influence clinical practice going forward.

Palandri is a medical doctor and an adjunct professor in the Department of Medical and Surgical Sciences at the University of Bologna in Italy.

OncLive: What was the design of SIMPLIFY-1, and what findings from this trial have been previously presented?

Palandri: The SIMPLIFY-1 trial is a prospective randomized trial including patients with myelofibrosis with splenomegaly and symptoms. These patients were randomly assigned to receive either momelotinib at 200 mg once a day, or ruxolitinib at 20 mg twice a day in the frontline setting.2 After 24 weeks, there was a possibility [for patients in the ruxolitinib arm] to cross over [to the momelotinib arm].

This trial was the first and only to compare 2 JAK2 inhibitors in the frontline setting in myelofibrosis and demonstrated the noninferiority of momelotinib over ruxolitinib in achieving spleen response. There was higher efficacy with ruxolitinib regarding symptom control. However, SIMPLIFY-1 was important because [we] demonstrated the ability of momelotinib to improve hemoglobin levels and therefore heal anemia in myelofibrosis for the first time.

What were the key findings from this subgroup analysis of dual response?

In this subgroup analysis, we wanted to focus only on the patients who started momelotinib with hemoglobin [levels] less than 10 g/dL, because this is [an] actual population that is going to be treated in the real-world setting.3 We wanted to understand the magnitude of a dual response, which means spleen and TI response with momelotinib or ruxolitinib. The dual response was significantly higher for the patients who received momelotinib compared with [those who received] ruxolitinib. This was particularly true when the platelet count of a patient was below 200 x 109/L, but this was also maintained when the platelet count was higher than 200 x 109/L. In a sense, even if we can achieve higher rates of spleen responses with ruxolitinib, if a platelet count is above 200 x 109/L, that spleen response comes at the expense of increased hematological toxicity and the need for transfusion.

This is important because we took a step forward and tried to correlate the ability to achieve a dual response with prognosis. We [conducted] a Kaplan-Meier analysis of OS, and we [divided patients into] subgroups according to the response that we observed at 24 weeks. For the patients achieving a TI response with or without a spleen response, the prognosis was much better, with a prolongation of OS.

What are the clinical implications of these subgroup analysis findings?

These results are important because, maybe for the first time, we showed that the condition of TI at week 24 is much more prognostically important compared with spleen control. We are moving our target of treatment from just spleen/symptom control to also the resolution of anemia. This is important new clinical information.

References

1. Ojaara (momelotinib) approved in the US as the first and only treatment indicated for myelofibrosis patients with anaemia. News release. GlaxoSmithKline. September 15, 2023. Accessed July 29, 2025. https://www.gsk.com/en-gb/media/press-releases/ojjaara-momelotinib-approved-in-the-us-as-the-first-and-only-treatment-indicated-for-myelofibrosis-patients-with-anaemia
2. Momelotinib (Ojjaara) Prescribing information. GlaxoSmithKline; revised April 2025. Accessed July 29, 2025. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Ojjaara/pdf/OJJAARA-PI-PIL.PDF
3. Palandri F, Schaap NPM, Rey J, et al. Impact of dual spleen response and transfusion independence on survival in JAK inhibitor–naive patients with myelofibrosis and anemia treated with momelotinib: a subgroup analysis of SIMPLIFY-1. Presented at: 2025 EHA Congress. June 12-15, 2025; Milan, Italy. Abstract PS1829.