ASC Therapy Does Not Show Significant Difference Over Placebo in Treating Xerostomia

Adipose-derived mesenchymal stem/stromal cell (ASC) therapy did not significantly improve xerostomia in patients with previous head and neck cancer compared with placebo, according to results of a single-center, phase 2, randomized trial (NCT04776538).

Data from the trial were published in an online paper for the American Association for Cancer Research (AACR) Annual Meeting 2024, held on April 5-10, 2024, in San Diego, California.

“No effective treatment exists for radiation-induced xerostomia. The objective of this study was to compare the effect of ASC injection, relative to placebo, on salivary gland function in patients with radiation-induced xerostomia,” first author Kathrine Kronberg Jakobsen, MD, PhD, Department of Otorhinolaryngology, Head and Neck Surgery & Audiology, Copenhagen University Hospital- Rigshospitalet, and Section for Biostatistics and Evidence-Based Research, the Parker Institute, Copenhagen University Hospital- Bispebjerg and Frederiksberg, Denmark, and colleagues wrote. The trial was conducted at Copenhagen University Hospital- Rigshospitalet.

Jakobsen and colleagues assessed 120 patients with previous head and neck cancer that received ultrasound-guided injections of allogeneic ASCs or placebo into the submandibular glands. These patients were between the ages of 18 and 75 years and were previously treated with radiotherapy chemotherapy in Denmark. Participants had clinically reduced salivation, with unstimulated whole salivary flow rate (UWS) between 0.05 and 0.25 mL per minute, and had to have had 2 years of recurrence-free follow-up. Exclusion criteria included other cancers in the past 4 years, xerogenic medications, penicillin or streptomycin allergy, known salivary gland disease, prior submandibular gland surgery or stem cells in the salivary glands, pregnancy, breastfeeding, or recent history of smoking or alcohol abuse.

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The investigators found that UWS statistically significantly increased by 0.04 mL per minute (38%) after ASC therapy (95% CI, 0.02-0.06) compared with baseline. UWS did not significantly increase from baseline after placebo treatment (increase, 0.01 mL/minute; 21%; [95% CI, 0.01-0.04])

“We could not confirm superiority of the ASC relative to placebo. ASC therapy significantly improved UWS in previous patients with head and neck cancer, whereas placebo resulted in an insignificant increase,” Jakobsen and colleagues wrote.

Change in patient-reported xerostomia was evaluated by the European Organization for Research and Treatment of Cancer Head and Neck questionnaire (EORTC QLQ-H&N35) and the Xerostomia Questionnaire (XQ). Patients reported notable symptom reductions with both ASC and placebo therapy, with reductions in dry mouth (ASC, 13.6 units; placebo, 7.7 units), sticky saliva (ASC, 14.8 units; placebo, 9.3 units), swallowing difficulties (ASC, 7.9 units; placebo, 8.0 units), and summary score of the XQ (ASC, 5.9 units; placebo, 5.1 units). There were no statistically significant group differences between the ACS and placebo arms for any outcomes.

In terms of safety, there were no deaths during the 4-month study period. Serious adverse events (AEs) unrelated to treatment occurred in 2 patients in the placebo arm and 1 in the ASC arm. Related AEs occurred in 15 patients (7.5%), these included temporary swelling of the submandibular glands in 9 patients receiving ASC therapy which disappeared after 1 day to 3 weeks. Temporary hematoma occurred in 2 patients (1.7%), 1 receiving ASCs and 1 receiving placebo. One patient had a near syncope during placebo injection. The submandibular injection was accompanied by pain in all participants which quickly subsided in 1-2 minute in most patients, although 3 (3.5%) had temporary soreness of salivary glands for 1-to-2 days (2 ASC, 1 placebo).

“There was no statistically significant difference between the two groups. In addition, we confirmed the safety of ASC treatment. We recommend that the potential effect of intraglandular ASC therapy should be evaluated in a phase III, multicenter study,” Jakobsen and colleagues concluded.

REFERENCE

Jakobsen KK, Carlander ALF, Todsen T, et al. Mesenchymal Stem/Stromal Cell Therapy for Radiation-Induced Xerostomia in Previous Head and Neck Cancer Patients: A Phase II Randomized, Placebo-Controlled Trial. Clin Cancer Res(2024): OF1–OF7. doi: 10.1158/1078-0432.CCR-23-3675