Characteristics of relapsed/refractory diffuse large B‐cell lymphoma patients with durable responses to maveropepimut‐S, pembrolizumab, and cyclophosphamide: Long‐term follow‐up from the SPiReL trial

Introduction: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have an unmet medical need. The objective of this trial was to assess the efficacy and toxicities of a novel triple immunotherapy regimen-pembrolizumab, low-dose cyclophosphamide, and maveropepimut-S (MVP-S). This regimen was designed to activate tumor-specific T cells by targeting the tumor-associated antigen survivin with MVP-S and reducing two important T cell inhibitory pathways: T cell exhaustion and regulatory T cells with pembrolizumab and metronomic cyclophosphamide, respectively. Methods: This was a single-arm Phase II clinical trial in 25 participants with R/R DLBCL-SPiReL trial (NCT03349450). Results: The median overall survival was 10.1 months and a third of participants survived over 2 years. Enhanced long-term survival was associated with favorable clinical characteristics and enhanced immune reactivity, as assessed by ELISpot and ISR-immune reactive responses. The regimen was well-tolerated with minimal Grade 3-4 toxicities. Conclusion: Combination immunotherapy regimens such as this could offer a promising alternative to other treatments with significant toxicities for select patients.