Abstract CT066: Therapeutic advances for high-risk and steroid-refractory aGvHD: Promising results from the phase 1b study of MSCTC-0010 Wharton's jelly mesenchymal stem cells (WJMSC)

Abstract Introduction: MSCTC-0010, an umbilical cord-derived mesenchymal stromal cell product with potent immunosuppressive effects, was studied in a First-in-Human Phase 1b Expansion Cohort study in patients with high-risk or steroid-refractory aGvHD. Patients with steroid-refractory aGvHD historically have >90% mortality risk. Although ruxolitinib was approved in 2021 as the first second-line treatment for steroid-refractory aGvHD, there is still significant unmet need, highlighting the importance of developing new and effective therapies. Methods: Patients aged 18-75 years who had previously undergone allogeneic stem cell transplant and developed high-risk or steroid-refractory aGvHD were enrolled. Patients met eligibility criteria if they had failed to respond to systemic steroid treatment (progression within 3 days or no improvement within 7 days of consecutive treatment with 1.6 mg/kg/d of methylprednisolone/equivalent) and/or were classified as high-risk by Minnesota criteria. Enrolled patients received 1-4 weekly infusions of MSCTC-0010 at a dose of either 2 × 106 cells/kg (first 10 patients) or 10 × 106 cells/kg (subsequent 14 patients). The primary endpoint for the study was the proportion of patients without treatment-related adverse events by Day 42. Results: Of the 26 patients screened for inclusion on the trial, 24 patients were enrolled and treated with MSCTC-0010. The cohort included 16 males (66%) with a median age of 59 years (IQR: 55-65). Thirteen patients (54%) were steroid-refractory, 2 (8%) were high-risk, and 9 (38%) were both. No treatment-related adverse events were observed in any patient. In follow-up, 3 patients (13%) experienced a relapse of their primary malignancy, and 14 patients (58%) died, with a median survival of 7.1 months (IQR 1.6-NR mo). Importantly, patients receiving all planned doses demonstrated a median survival of 30 months (IQR 4.4-NR mo). The median follow-up for all trial patients was 5 months (range: 9 days - 70 months). Comparatively, these findings are consistent with, and may be superior to data from the pivotal REACH2 trial, where ruxolitinib-treated patients demonstrated approximately 50% mortality and a median overall survival of 11.1 months. Conclusions: MSCTC-0010 trial demonstrated a favorable safety profile and comparable efficacy to currently FDA-approved therapies for aGVHD. These results support further investigation of MSCTC-0010 in phase II trials as an adjunct therapy for high-risk and steroid refractory aGvHD patients. Citation Format: William C. Wesson, Jianzheng Wu, Milind Phadnis, Scott Weir, Tyce Bruns, Haitham Abdelhakim, Rupal Soder, Ramesh Balusu, Sunil Abhyankar, Joseph P. McGuirk. Therapeutic advances for high-risk and steroid-refractory aGvHD: Promising results from the phase 1b study of MSCTC-0010 Wharton's jelly mesenchymal stem cells (WJMSC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT066.