MAIC Points to Improved OS With Momelotinib in Ruxolitinib-Pretreated Myelofibrosis

Momelotinib (Ojjaara) demonstrated improved overall survival (OS) vs best available therapy (BAT) in patients with ruxolitinib (Jakafi)–pretreated myelofibrosis, according to data from a matching-adjusted indirect comparison (MAIC) analysis that were presented at the 2024 ASH Annual Meeting & Exposition.1

Data from an unmatched analysis demonstrated that the median OS favored patients who received momelotinib (n = 383) compared with those who received BAT (n = 267; HR, 0.373; 95% CI, 0.297-0.469; P < .001). In the base case model (model 1), the median OS also favored momelotinib (n = 89) vs BAT (HR, 0.512; HR, 0.358-0.732; P < .001). In the alternative adjustment model (model 2), the median OS again favored momelotinib (n = 117) vs BAT (HR, 0.484; 95% CI, 0.347-0.675; P < .001).

Additionally, patients in the anemia subgroup who received momelotinib (n = 255) experienced a median OS benefit compared with those treated with BAT (n = 174; HR, 0.384; 95% CI, 0.293-0.504; P < .001). Data from model 1 also showed that patients treated with momelotinib in this subgroup (n = 98) achieved a median OS benefit vs those in the BAT arm (HR, 0.542; 95% CI, 0.387-0.759; P < .001). Findings from model 2 demonstrated a median OS benefit with momelotinib (n = 146) vs BAT (HR, 0.487; 95% CI, 0.360-0.660; P < .001).

“[Although] the trials used in this analysis do no provide long-term outcomes, this MAIC suggests that momelotinib may offer a greater OS benefit than BAT in patients with myelofibrosis previously treated with ruxolitinib, both in the overall cohort and the anemic population,” Francesca Palandri, MD, PhD, lead study author and an adjunct professor in the Department of Medical and Surgical Sciences at the University of Bologna in Italy, said in a poster presentation of the data.

In September 2023, the FDA approved momelotinib for the treatment of adult patients with intermediate or high-risk myelofibrosis, including primary myelofibrosis or secondary myelofibrosis, and anemia.2 The regulatory decision was supported by findings from the phase 3 MOMENTUM (NCT04173494) and SIMPLIFY-1 trials (NCT01969838).

To conduct their analysis, Palandri and colleagues performed a MAIC analysis comparing patients who received momelotinib during MOMENTUM, SIMPLIFY-1, or the phase 3 SIMPLIFY-2 trial (NCT02101268) with 267 patients who received BAT across 26 European hematology centers in the real-world, retrospective RUX-MF study.1 Notably, the overall study included 1055 patients treated with ruxolitinib across 26 European hematology centers from 2013 until death or the data cutoff of February 2, 2024.

Eligible patients had myelofibrosis and had received momelotinib or BAT as second-line therapy. BAT comprised hydroxyurea, danazol, corticosteroids, erythropoiesis-stimulating agents, and other investigational agents beyond momelotinib. The comparison was performed among patients in the chronic phase, thereby excluding those in the accelerated or blast phase. The anemic subgroup was defined as patients who had hemoglobin levels less than 10 g/dL.

Patients who had received momelotinib were reweighted to match the BAT population using 2 models with different matching factors. Models 1 and 2 both used patient age, male sex, BMI above 25 kg/m2, myelofibrosis subtype, and Dynamic International Prognostic Dynamic International Prognostic Scoring System for Myelofibrosis risk score as matching factors. Model 1 also utilized hemoglobin levels less than 10 g/dL, white blood cell counts above 25 x 109/L, spleen length of at least 10 cm, and total symptom score as matching factors.

The mean patient age at baseline across the BAT group, model 1, and model 2 was 71.5 years. Most patients in each group were male (58.4%), had primary myelofibrosis (51.7%), and had hemoglobin levels less than 10 g/dL (65.2% in BAT group; 65.2% in model 1; 67.3% in model 2). High-risk disease was present in 15.4% of patients in each arm; 51.7% of patients in each arm had intermediate-2-risk disease.

Additional findings from the MAIC analysis revealed that, when patients randomly assigned to ruxolitinib in SIMPLIFY-1 were excluded from the sensitivity analysis, there was still a median OS benefit with momelotinib over BAT with both model 1 (HR, 0.479; 95% CI, 0.292-0.786; P = .004) and model 2 (HR, 0.512; 95% CI, 0.330-0.797; P = .003). These data were excluded to remove potential survival effects from patients who were JAK inhibitor–naive or received ruxolitinib for 24 weeks prior to the study.

There was also a median OS benefit with momelotinib compared with BAT using model 1 (HR, 0.551; 95% CI, 0.379-0.800; P = .002) and model 2 (HR, 0.521; 95% CI, 0.366-0.742; P < .001) with population matching when patients randomly assigned to receive momelotinib in MOMENTUM were excluded. These data were excluded to remove the potential effects of COVID-19 on survival outcomes.

In the anemia subgroup, there was a median OS benefit with momelotinib over BAT using model 1 (HR, 0.502; 95% CI, 0.335-0.754; P = .001) and model 2 (HR, 0.503; 95% CI, 0.351-0.722; P < .001) with population matching when data from SIMPLIFY-1 were excluded. Similarly, there was a median OS benefit with momelotinib compared with BAT using model 1 (HR, 0.678; 95% CI, 0.457-1.005; P = .053) and model 2 (HR, 0.546; 95% CI, 0.394-0.757; P < .001) with population matching when data from MOMENTUM were excluded.

“Together with the results of SIMPLIFY-2 trial and MOMENTUM, these data further support the use of momelotinib as a standard of care in patients with myelofibrosis and anemia in this setting,” Palandri concluded.

Disclosures: Dr Palandri did not share any relevant disclosures.

References

1. Palandri F, Kapetanakis V, Dobi B, et al. Overall survival with momelotinib vs best available therapy in patients with ruxolitinib-experienced myelofibrosis: a matching-adjusted indirect comparison. Blood. 2024;144(suppl 1):3187. doi:10.1182/blood-2024-205973
2. 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 December 10, 2024. 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