3611 - A Pilot, First in Human Study of Autologous IFN-Gamma Stimulated Mesenchymal Stromal Cells for Treatment of Radiation-Induced Xerostomia - Results of Contralateral Injections

G. C. Blitzer¹, T. Glazer², S. Gustafson³, A. Burr⁴, R. Pena², R. Mattison², O. Ganz², R. Meyers², M. Weiss⁴, K. McDowell², K. P. Nickel⁵, R. J. Chappell², N. Pulia³, J. Gallipeau², and R. J. Kimple⁵; ¹Department of Human Oncology, University of Wisconsin Hospital and Clinics, Madison, WI, ²University of Wisconsin, Madison, WI, ³Department of Communication Sciences and Disorders, Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, ⁴Department of Human Oncology, University of Wisconsin Hospitals and Clinics, Madison, WI, ⁵Department of Human Oncology, University of Wisconsin, Madison, WI

Purpose/Objective(s): There are no existing effective treatments for radiation-induced xerostomia (RIX), a common side effect of head and neck radiation. Mesenchymal stromal cells (MSCs) exhibit regenerative effects in multiple tissues and may represent an effective cell therapy for the treatment of RIX. Here we present the updated primary safety and secondary efficacy endpoints of a first-in-human pilot study of IFN?-stimulated autologous bone marrow- derived MSCs [MSC(M)] injected into bilateral submandibular glands for the treatment of RIX. Materials/

Methods: We conducted a single-center clinical trial investigating the safety and tolerability of autologous IFN?-stimulated MSC(M). The study was conducted under an FDA-IND. Patients underwent bone marrow aspiration, MSC(M) were then cultured, stimulated with IFN?, and cryopreserved. Banked IFN?-stimulated MSC(M) were thawed, allowed to recover, and then 10x10⁶ MSC(M) were injected into one submandibular gland. After initial results demonstrated safety, the IND was amended to permit injection of the contralateral submandibular gland. The primary objective was safety and tolerability determined by dose-limiting toxicity (DLT) defined as submandibular pain > 5 on a standard 10-point pain scale or any serious adverse event (SAE) within one month after injection. Secondary objectives included analysis of efficacy as measured by salivary quantification and 3 validated quality of life instruments.

Results: Six radiation-induced xerostomia patients who had completed radiation at least 2 years earlier were enrolled. The median age was 71 (61-74), five (83%) patients were male. Four patients have been injected in the contralateral gland with the final two patients to undergo injection in spring of 2024. The contralateral gland was injected an average of 397 days after the first injection (range 210-630 days). One patient reported a pain score of 1 after submandibular gland injection, all pain resolved within 3 days. No SAEs or other DLTs were reported at the 1 month follow-up after contralateral injection. All patients reported improved or stable quality of life and stable salivary production. Salivary quantification data and updated events with all six patients will be presented.

Conclusion: Injection of autologous IFN?-stimulated MSC(M) into both submandibular glands of patients with RIX is safe and well tolerated. A trend towards an improvement in secondary endpoints of salivary quantity and quality of life was observed at 1 month after contralateral injection. This first-in-human pilot study provides support for further investigation into IFN?-stimulated MSC(M) as an innovative, potentially curative, remedy to treat RIX and restore quality of life. A phase I dose-escalation study injecting into bilateral submandibular glands is accruing at our institution.