Real-world evidence confirms that ruxolitinib (Jakafi) demonstrates sustained therapeutic activity in patients with chronic graft-versus-host disease (cGVHD), while emerging combination strategies show promise for improving outcomes in this challenging condition.
Real-World Evidence Supports Sustained Ruxolitinib Activity
A retrospective analysis of 471 adult and pediatric patients with cGVHD revealed that ruxolitinib maintains enduring activity in clinical practice, with one-third of patients continuing treatment for extended periods. The study, presented at the 2024 Tandem Meeting, showed that 33.1% of patients remained on ruxolitinib treatment at the end of follow-up, achieving a median duration of treatment of 389 days.
The analysis utilized the Komodo Healthcare Map database, including patients who received allogeneic hematopoietic cell transplantation and were diagnosed with cGVHD between January 2019 and November 2022. Patients had a mean age of 42.6 years, with 15.3% under 18 years old and 10.6% over 65 years old. The median baseline Charlson Comorbidity Index score was 2.0, with common comorbidities including anemia (77.7%), nutritional disorders (72.4%), and skin disorders (72.0%).
Ruxolitinib was predominantly used as second-line therapy (45%), followed by third-line (31%) treatment. The median time to treatment discontinuation was 245 days, with no significant difference between pediatric (286 days) and adult patients (243 days). Notably, 58.4% of patients who refilled their medication required dose adjustments, with 55.9% receiving dose increases and 44.1% receiving dose decreases as the first modification.
Combination Therapy Demonstrates Synergistic Potential
A separate study of 20 patients explored the efficacy of combining ruxolitinib with belumosudil (Rezurock) for cGVHD treatment. The combination achieved a 55% overall response rate, including one complete response (5%) and seven partial responses (35%). Importantly, among three patients who had not responded to either agent as monotherapy, the combination therapy resulted in one complete response and two partial responses.
The median time to response was 91 days, with a duration of response of 48 days. All patients who responded to the combination therapy were able to decrease or discontinue other immunosuppressive agents. The study included patients who had undergone allogeneic hematopoietic cell transplantation and developed cGVHD, with the majority being female (60%) and receiving myeloablative conditioning regimens (65%).
Safety Profile and Clinical Considerations
The combination therapy demonstrated a manageable safety profile, though some adverse events were observed. Four patients (20%) developed pneumonia and two (10%) experienced upper respiratory infections. One patient required dose reduction of belumosudil due to side effects but tolerated the reduced dose. No patients developed cytomegalovirus, Epstein-Barr virus, graft failure, or disease relapse during the study period.
Treatment Patterns and Clinical Practice
In real-world practice, ruxolitinib was commonly administered as monotherapy (43.1%) or in combination with calcineurin inhibitors (37.2%) following corticosteroid treatment. The median starting dose was 10 mg daily in both pediatric and adult patients, though adult patients showed a wider dosing range. Patients typically initiated ruxolitinib after a median of 116 days from cGVHD diagnosis, with 88.3% having received corticosteroids and 76.0% having received calcineurin inhibitors in the six months prior.
Implications for Future Treatment Strategies
The investigators noted that the combination of ruxolitinib and belumosudil may provide synergistic effects by targeting different inflammatory pathways - ruxolitinib targets the JAK/STAT pathway while belumosudil targets ROCK2. This mechanistic rationale supports the observed clinical responses in patients who had previously failed monotherapy approaches.
The real-world data confirms that patients are receiving ruxolitinib for a median of approximately eight months, with about one-third deriving ongoing clinical benefit for over one year. Most patients appeared able to receive treatment at recommended dose levels and continue therapy successfully with appropriate dose adjustments when needed.
