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.