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Long-term Use of Ibrutinib in Japanese Patients with Steroid Dependent/Refractory cGVHD: Final Analysis of
Masako Toyosaki1, Noriko Doki2, Souichi Shiratori3
1Department of Hematology/Oncology, Tokai University School of Medicine, Kanagawa, Japan.
Insights
Extended follow-up confirms ibrutinib is effective and safe for Japanese patients with chronic graft-versus-host disease (cGVHD) refractory to steroids. The study shows a high response rate and manageable safety profile, supporting its use in this patient population.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Chronic graft-versus-host disease (cGVHD) is a significant complication following allogeneic stem cell transplantation.
- Patients with cGVHD who fail initial steroid treatments have a poor prognosis.
- Ibrutinib has demonstrated efficacy and safety in cGVHD patients, leading to its approval in Japan.
Purpose of the Study:
- To evaluate the long-term safety and efficacy of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD.
- To assess response rates, duration of response, and impact on corticosteroid use.
- To monitor for any new safety signals with prolonged ibrutinib exposure.
Main Methods:
- An open-label, single-arm, multicenter study involving Japanese patients with steroid-dependent or refractory cGVHD.
- Extended follow-up data collection after initial treatment with ibrutinib.
- Analysis of overall response rate, organ-specific response, sustained response, corticosteroid dose reduction, failure-free survival, overall survival, and treatment-emergent adverse events.
Main Results:
- An overall response rate of 84.2% was observed, with a median time to response of 2.81 months.
- Sustained responses were achieved in a significant proportion of patients (up to 68.8% for ≥20 weeks).
- A trend towards decreased corticosteroid dose requirement was noted, with 63.2% of patients reaching a low dose and 21.1% discontinuing steroids.
- Failure-free and overall survival rates at 30 months were 62.7% and 62.0%, respectively.
- The safety profile was consistent with previous findings, with common grade ≥3 TEAEs including pneumonia and decreased platelet count. No new safety concerns emerged with prolonged exposure.
Conclusions:
- Extended follow-up confirms that ibrutinib demonstrates a clinically meaningful response in Japanese patients with steroid-dependent or refractory cGVHD.
- Ibrutinib maintains an acceptable safety profile, even with prolonged exposure, in this patient population.
- These findings support the continued use of ibrutinib as a treatment option for steroid-refractory cGVHD.
Background:
Chronic graft-versus-host disease (cGVHD) is a serious complication after allogeneic stem cell transplantation. Poor prognosis has been shown in patients with cGVHD after the failure of primary steroid-based treatments. A previous report demonstrated the efficacy and safety of ibrutinib in these patients, leading to the approval of ibrutinib for cGVHD in Japan. Here, we report the extended follow-up of patients in this study.
Objectives:
To evaluate the safety and efficacy of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD.
Study Design:
An open-label, single-arm, multicenter study of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD (NCT No.: NCT03474679; Clinical Registry No.: CR108443).
Results:
At the time of the final data cutoff, 7/19 (36.8%) patients completed the study treatment, and 12/19 (63.2%) patients discontinued ibrutinib. After a median follow-up of 31.11 months (range:1.9 to 38.6 months), the best overall response rate was 84.2% (16/19 patients; 95% CI:60.4%, 96.6%) in all treated populations, with a median time to response of 2.81 (range:1.0 to 27.6) months. Of 15 responders with ≥2 organs involved at baseline, seven (46.7%) had responses in multiple organs. An improvement in the organ response rate was observed for the skin, eye, mouth, and esophagus compared with that in a previous report. The rate of sustained response for ≥20 weeks, ≥32 weeks, and ≥44 weeks were 68.8%, 62.5%, and 50.0%, respectively for 16 responders. The median daily corticosteroid dose requirement tended to decrease over time for all treated analysis sets. Twelve of 19 patients (63.2%) reached a corticosteroid dose of <0.15 mg/kg/day for at least one week, and four (21.1%) discontinued corticosteroid treatment for at least 28 days during the study. The failure-free and overall survival rates at 30 months were 62.7% and 62.0%, respectively. The safety findings of this updated analysis were consistent with the safety profile observed at the time of the primary analysis and the known ibrutinib safety profile. Common grade ≥3 treatment-emergent adverse events (TEAEs) were pneumonia (6/19 [31.6%] patients), platelet count decreased, and cellulitis (3/19 [15.8%] patients each). After the primary analysis, no new TEAEs leading to death, treatment discontinuation, or dose reduction were reported, and no new patients reported major hemorrhage. Cardiac arrhythmia (Grade 2 atrial flutter) was reported in 1/19 (5.3%) patients. No new safety signs were observed despite prolonged ibrutinib exposure.
Conclusions:
The final results support previous conclusions, demonstrating a clinically meaningful response and acceptable safety profile of ibrutinib in Japanese patients with steroid-dependent or refractory cGVHD.
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