Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis.
Ruxolitinib-based combination therapies show promising efficacy in JAK inhibitor-naïve patients, but treatment responses can vary significantly based on prior exposure.
Where it sits
this study against the rest of the selank corpusSummary and findings
This meta-analysis evaluated the efficacy and safety of Ruxolitinib-based combination therapies in patients with Myelofibrosis (MF). The study included 1,088 patients across 19 studies, focusing on spleen volume reduction and symptom score improvements. Not reported in abstract.
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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.
Background
This paper addresses the limitations of Ruxolitinib in treating Myelofibrosis (MF), particularly its inability to reverse disease progression and the frequent emergence of resistance. Prior studies have indicated the potential for combination therapies to enhance treatment outcomes by targeting pathways beyond the JAK-STAT axis. This systematic review and meta-analysis aims to synthesize existing data on the efficacy and safety of various Ruxolitinib-based combination therapies in MF patients.
Methods
The study conducted a systematic search of databases for relevant studies published through August 1, 2025. A total of 19 studies were included, comprising 1,088 patients. The primary efficacy endpoints were defined as ≥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, with subgroup analyses based on prior JAK inhibitor exposure.
Results
The primary endpoint of spleen volume reduction (SVR35) was achieved in 92% of JAK inhibitor-naïve patients receiving Ruxolitinib plus Selinexor. Additionally, TSS50 was reported at 78% for the same combination in this group. For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin demonstrated an SVR35 of 45%. Not reported in abstract.
Interpretation
The findings suggest that Ruxolitinib-based combination therapies can yield significant efficacy in JAK inhibitor-naïve patients, particularly with Selinexor. However, the effect sizes, while statistically significant, may not be clinically meaningful for all patients, especially those with prior treatment exposure. The study's limitations, including potential confounding factors and the variability in treatment responses, necessitate cautious interpretation of the results for clinical practice.
Key findings
- SVR35: 92% for Ruxolitinib plus Selinexor in JAK inhibitor-naïve patients.
- TSS50: 78% for Ruxolitinib plus Selinexor in JAK inhibitor-naïve patients.
- SVR35: 90% for Ruxolitinib plus BMS-986158 in JAK inhibitor-naïve patients.
- SVR35: 45% for Ruxolitinib plus Siremadlin in patients with prior JAK inhibitor exposure.
Limitations
- Heterogeneity of included studies.
- Potential publication bias.
- Impact of prior JAK inhibitor exposure complicates results.
- Not all safety endpoints reported in detail.