Long-term Results of Multiantigen Stimulated Cell Therapy I, Alone or in Combination with Chemotherapy, as First-line Maintenance Therapy in Advanced Sarcoma: A Multicenter, Phase I Trial

Purpose: Advanced sarcomas lack effective maintenance therapies after first-line chemotherapy. We present long-term phase I results evaluating multiantigen stimulated cell therapy I (MASCT-I), a novel immunotherapy integrating dendritic cell vaccination with adoptive T-cell transfer, as maintenance treatment (NCT03034304). Patients and Methods: Thirty-one patients with disease control after chemotherapy received MASCT-I alone (n ¼ 17) or with ifosfamide (n ¼ 14). The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), overall survival (OS), time to progression, objective response rate, and disease control rate. Exploratory objective comprised evaluation of the relationship between clinical efficacy and antigen-specific immune responses. Results: Treatment was well tolerated with no treatment-related deaths. After a median follow-up of 63.6 months, the median PFS from maintenance initiation (PFS1) was 9.5 months and that from first-line chemotherapy start (PFS2) was 16.2 months; the median OS was 33.8 months. The combination with ifosfamide numerically improved survival outcomes compared with mono-therapy. Patients with high antigen-specific immunity were significantly positively associated with prolonged survival. Notably, 6 of the 7 patients who maintained progression-free status for over 4 years exhibited robust immune activation. Conclusions: Our findings establish MASCT-I alone or combined with chemotherapy as maintenance treatment that elicits sustained antigen-specific immunity and encouraging survival in advanced sarcoma.