Long-term effect and safety of mesenchymal stromal cell therapy for radiation-induced hyposalivation in head and neck cancer survivors: A randomised, phase-2, trial.

Background: The long-term effect of adipose-derived mesenchymal stromal cells (ASCs) to restore radiation-induced salivary gland hypofunction in previous head and neck cancer patients have not been validated in larger settings.

Methods: The study was the 12-months follow-up of a randomised trial, including patients with hyposalivation. Patients were randomised to receive allogeneic ASCs or placebo in the submandibular glands. Primary endpoint was unstimulated whole saliva (UWS) followed by stimulated whole saliva, patient-reported outcomes (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Head and Neck Module and the Xerostomia Questionnaire) and safety.

Results: Of the 120 enrolled patients, 117 (97.5%) were assessed at 12 months. Treatment with ASCs did not increase UWS compared to placebo: increase in UWS was 0.02 mL/min (95% CI 0.01 to 0.04) in the ASC group and 0.02 mL/min (95% CI 0 to 0.03) in the placebo group, p=0.56. ASCs reduced the symptom burden for dry mouth with -10.07 units (95% CI -13.39 to -6.75) compared to -4.15 units (95% CI -7.46 to -0.84) in the placebo group, p=0.01. Compared to placebo, ASCs did not improve sticky saliva (-9.27 vs. -4.55 units, p=0.13), swallowing (-4.50 vs. 3.49 units, p=0.5) or xerostomia -3.12 vs. -2.74 units, p=0.82). Treatment was safe and associated with a transient immune response.

Conclusion: Intraglandular ACS therapy in the submandibular glands significantly relieved subjective dry mouth symptoms. Both ASCs and placebo increased UWS, but ASCs did not prove superior to placebo in restoring salivary gland function, based on salivary flow rate.