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Background <p>Allogenic stem cell transplantation (SCT) is the only curative option for many hematologic disorders. However, graft versus host disease (GVHD) remains a major limitation. Systemic steroids are the cornerstone for therapy but steroid refractoriness (SR) is expected in about 50% of cases. Recently, Ruxolitinib was approved as a second line therapy for SR-GVHD.</p> Aim <p>To quantitatively analyse the available evidence about efficacy and safety of Ruxolitinib therapy in SR-GVHD. Also, to explore the potential role of Ruxolitinib as GVHD prophylaxis and first line therapy.</p> Methods and results <p>A meta-analysis based on results from 43 trials with total of 3153 patients. 34 trials used Ruxolitinib therapy for SR-GVHD, 6 trials utilised Ruxolitinib as prophylaxis and 3 trials utilised Ruxolitinib as first line therapy.</p> <p>For utilisation in SR-GVHD, primary end point was the overall response rate (ORR). Secondary end points were complete response (CR) rate, overall survival (OS), rate of adverse events. In SR-aGVHD ORR was 0.72 which is quite close to its effect in SR-cGVHD of 0.74. However, complete response (CR) rate in SR-aGVHD was 0.42 while in SR-cGVHD CR rate was 0.15. Age was independent variable to determine the CR rate in SR-aGVHD. Age &lt; 50 ys had CR rate of 0.54, while age &gt; 50 ys had CR rate of 0.35 and P = 0.01. Further analysis revealed that ORR in SR-aGVHD was significantly better when Ruxolitinib was combined with other immune suppressive therapies (IST) apart from calcineurin inhibitors (CNI). ORR post Ruxolitinib + IST was 0.82 with 95% CI 0.72–0.91 while ORR post Ruxolitinib ± CNI was 0.68 with 95% CI 0.61–075 and P = 0.02. Overall survival (OS) post Ruxolitinib in SR-aGVHD was 0.64 while in SR-cGVHD, OS was 0.83. Relapse rate in SR-cGVHD was 0.071. Main adverse effects included infections, particularly CMV reactivation and cytopenias. Rate of Cytopenias in SR-aGVHD and SR-cGVHD were 0.505 and 0.179 respectively. Using Ruxolitinib as prophylaxis also showed encouraging results. Rate of aGVHD grade II-IV was 0.18 and cGVHD was 0.28. Engraftment rate was 0.93 and OS post Ruxolitinib prophylaxis was 0.89. Also, Ruxolitinib use as first line therapy with steroids for acute GVHD showed response rate of 0.889. Non-relapse mortality (NRM) rate was 0.118 and relapse rate was 0.19.</p> Conclusion <p>Ruxolitinib represents an effective therapeutic option for SR-GVHD, acute and chronic. ORR seems comparable between acute and chronic SR-GVHD but CR rate is higher in SR-aGVHD. However, adverse effects were more frequent in acute SR-GVHD. The best ORR in SR-aGVHD was related to Ruxolitinib in combination with other IST apart from CNI. Also, dose of 5&#xa0;mg BD seems safe as prophylaxis as well as first line therapy in addition to steroids.</p>

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The JAK1/2 inhibitor Ruxolitinib as therapeutic option in steroid resistance, prophylaxis and frontline therapy for graft versus host disease, meta-analysis

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  • 发表日期：

    2025年7月9日

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  • Mohammed Debes,
  • Amr Elyasaky,
  • Mohamed Abouzeid,
  • Ramy Elantary,
  • Zaeem Mahmood,
  • Robert Downey,
  • Ahmed Yassiri

摘要

Background

Allogenic stem cell transplantation (SCT) is the only curative option for many hematologic disorders. However, graft versus host disease (GVHD) remains a major limitation. Systemic steroids are the cornerstone for therapy but steroid refractoriness (SR) is expected in about 50% of cases. Recently, Ruxolitinib was approved as a second line therapy for SR-GVHD.

Aim

To quantitatively analyse the available evidence about efficacy and safety of Ruxolitinib therapy in SR-GVHD. Also, to explore the potential role of Ruxolitinib as GVHD prophylaxis and first line therapy.

Methods and results

A meta-analysis based on results from 43 trials with total of 3153 patients. 34 trials used Ruxolitinib therapy for SR-GVHD, 6 trials utilised Ruxolitinib as prophylaxis and 3 trials utilised Ruxolitinib as first line therapy.

For utilisation in SR-GVHD, primary end point was the overall response rate (ORR). Secondary end points were complete response (CR) rate, overall survival (OS), rate of adverse events. In SR-aGVHD ORR was 0.72 which is quite close to its effect in SR-cGVHD of 0.74. However, complete response (CR) rate in SR-aGVHD was 0.42 while in SR-cGVHD CR rate was 0.15. Age was independent variable to determine the CR rate in SR-aGVHD. Age < 50 ys had CR rate of 0.54, while age > 50 ys had CR rate of 0.35 and P = 0.01. Further analysis revealed that ORR in SR-aGVHD was significantly better when Ruxolitinib was combined with other immune suppressive therapies (IST) apart from calcineurin inhibitors (CNI). ORR post Ruxolitinib + IST was 0.82 with 95% CI 0.72–0.91 while ORR post Ruxolitinib ± CNI was 0.68 with 95% CI 0.61–075 and P = 0.02. Overall survival (OS) post Ruxolitinib in SR-aGVHD was 0.64 while in SR-cGVHD, OS was 0.83. Relapse rate in SR-cGVHD was 0.071. Main adverse effects included infections, particularly CMV reactivation and cytopenias. Rate of Cytopenias in SR-aGVHD and SR-cGVHD were 0.505 and 0.179 respectively. Using Ruxolitinib as prophylaxis also showed encouraging results. Rate of aGVHD grade II-IV was 0.18 and cGVHD was 0.28. Engraftment rate was 0.93 and OS post Ruxolitinib prophylaxis was 0.89. Also, Ruxolitinib use as first line therapy with steroids for acute GVHD showed response rate of 0.889. Non-relapse mortality (NRM) rate was 0.118 and relapse rate was 0.19.

Conclusion

Ruxolitinib represents an effective therapeutic option for SR-GVHD, acute and chronic. ORR seems comparable between acute and chronic SR-GVHD but CR rate is higher in SR-aGVHD. However, adverse effects were more frequent in acute SR-GVHD. The best ORR in SR-aGVHD was related to Ruxolitinib in combination with other IST apart from CNI. Also, dose of 5 mg BD seems safe as prophylaxis as well as first line therapy in addition to steroids.