Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis

Myelofibrosis (MF) is a chronic myeloproliferative neoplasm. Although Ruxolitinib, a JAK1/2 inhibitor, remains the cornerstone of MF treatment, it does not reverse disease progression, and resistance frequently emerges. These limitations have prompted investigation into combination therapies targeting pathways beyond the JAK-STAT axis. This meta-analysis aims to evaluate the efficacy and safety of Ruxolitinib-based combination therapies in patients with MF.
We conducted a systematic search of databases for studies published through August 1, 2025. Thirteen distinct Ruxolitinib-based combination regimens were included. Primary efficacy endpoints were ≥35% spleen volume reduction at 24 weeks (SVR35) and ≥50% reduction in total symptom score (TSS50). Safety endpoints focused on the incidence of grade 3/4 thrombocytopenia and anemia. Subgroup analyses were performed based on prior JAK inhibitor exposure and therapeutic mechanism of action.
A total of 19 studies comprising 1,088 patients were included in the meta-analysis. Among JAK inhibitor-naïve patients, the combination of Ruxolitinib with Selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by Ruxolitinib plus BMS-986158 (SVR35: 90%). For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin (SVR35: 45%) showed notable activity.
For JAK inhibitor-naïve patients, Ruxolitinib-based combination regimens demonstrated satisfactory clinical responses and the potential for meaningful disease control. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure.

This is the first systematic meta-analysis evaluating Ruxolitinib-based combination therapies for myelofibrosis (MF). Overall, combination regimens demonstrated in clinical studies, showing improved spleen and symptom responses with an acceptable safety profile.
Selinexor is an XPO1 inhibitor, while BMS-986158 are BET inhibitors. Combinations of Ruxolitinib with these two agents exhibited satisfactory efficacy in JAK inhibitor–naïve patients and might be promising options. In previously treated patients, Ruxolitinib plus Siremadlin might be a relatively recommended regimen.
Combinations of Ruxolitinib with IFN-α, Pelabresib, Navitoclax, 5-azacitidine (5-AZA), Buparlisib, or Panobinostat showed moderate efficacy in JAK inhibitor–naïve patients.
The efficacy of a given regimen varies significantly depending on prior exposure to JAK inhibitors.

This is the first systematic meta-analysis evaluating Ruxolitinib-based combination therapies for myelofibrosis (MF). Overall, combination regimens demonstrated in clinical studies, showing improved spleen and symptom responses with an acceptable safety profile.
Selinexor is an XPO1 inhibitor, while BMS-986158 are BET inhibitors. Combinations of Ruxolitinib with these two agents exhibited satisfactory efficacy in JAK inhibitor–naïve patients and might be promising options. In previously treated patients, Ruxolitinib plus Siremadlin might be a relatively recommended regimen.
Combinations of Ruxolitinib with IFN-α, Pelabresib, Navitoclax, 5-azacitidine (5-AZA), Buparlisib, or Panobinostat showed moderate efficacy in JAK inhibitor–naïve patients.
The efficacy of a given regimen varies significantly depending on prior exposure to JAK inhibitors.