Talimogene Laherparepvec combined with anti-PD-1 based immunotherapy for unresectable stage III-IV melanoma: a case series

Abstract

BackgroundTalimogene Laherparepvec (T-VEC) is an oncolytic virus approved as an intratumoral therapy for treating unresectable stage IIIB-IV metastatic melanoma. The mechanisms of action for T-VEC and checkpoint inhibitor are highly complementary. Recent studies have shown that combining checkpoint inhibitor therapy with T-VEC injection can lead to improved response rates for stage IIIB-IV melanoma patients.MethodsWe reviewed 10 consecutive cases of stage IIIC to stage IVM1b melanoma patients that received T-VEC plus checkpoint inhibitor(s) therapy (pembrolizumab, ipilimumab/nivolumab, or nivolumab) treated between June 2016 and August 2017 at the Cleveland Clinic with a median follow-up of 7 months (range: 4 to 13 months). Responses of injected (on-target) and uninjected (off-target) lesions were evaluated according to RECIST 2.0.ResultsThe overall response rate for on-target lesions was 90%, with 6 patients experiencing a complete response in injected lesions. Two patients had off-target lesions, which were completely resolved after treatment. Blood samples were tested for 3 complete responders and 2 partial responders. CD4:CD8 ratio and frequencies of circulating PD1+ CD4 and CD8 T cells were elevated in complete responders but not partial responders. One patient died due to causes unrelated to melanoma and one patient died of progression of the disease.ConclusionOur data suggest that combining checkpoint inhibitor(s) with T-VEC injection may provide a synergistic efficacy for patients with unresectable melanoma. We observed a better overall response rate and complete response rate compared to published studies on similar therapeutic regimens.

Survival Comparison between Melanoma Patients Treated with Patient-Specific Dendritic Cell Vaccines and Other Immunotherapies Based on Extent of Disease at the Time of Treatment

“…The rationale for combining DC-ATA with checkpoint inhibitors also applies to this cytolytic virus product, namely the potential immune recognition of additional ATA. Encouraging results have been reported for combining this agent with anti-CTLA-4 and anti-PD-1 agents [46,47]. Combining DCV with intralesional cytolytic virus injection may be additive or synergistic because of the direct anti-tumor effects of the cytolytic virus.…”

Development of oncolytic virotherapy: from genetic modification to combination therapy

“…with anti-PD-1 antibody for unresectable stage III-IV melanoma treatment, leading to an overall response rate (on-target lesions) of 90% (9/10) [201].…”

The histological spectrum of talimogene laherparepvec (TVEC) injections—Neutrophilic and chronic granulomatous dermatitis

“…We also contribute a case of cutaneous metastatic melanoma treated concurrently with TVEC and pembrolizumab, an anti‐PD1 immunotherapy, resulting in similar post‐injection robust lymphocytic infiltrate. A case series by Sun et al suggests that the combination of TVEC injections with checkpoint inhibitors such as pembrolizumab may provide a synergistic benefit. Of interest, Parekh et al also reported a case of TVEC administration inducing a neutrophilic (Sweet‐like) infiltrate.…”