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Case Reports
. 2018 May 16;6(1):36.
doi: 10.1186/s40425-018-0337-7.

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

Lillian Sun  1 , Pauline Funchain  2 , Jung Min Song  3 , Patricia Rayman  4 , Charles Tannenbaum  5 , Jennifer Ko  6   7 , Michael Mcnamara  8 , C Marcela Diaz-Montero  9 , Brian Gastman  10   11   12   13   14
Affiliations
Case Reports

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

Lillian Sun et al. J Immunother Cancer. .

Abstract

Background: Talimogene 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.

Methods: We 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.

Results: The 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.

Conclusion: Our 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.

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Conflict of interest statement

Authors’ information

Not applicable.

Ethics approval and consent to participate

The study was approved by the Cleveland Clinic Institutional Review Boards.

Consent for publication

Informed consent has been obtained and are held by the authors.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Timing of treatments. The time of T-VEC injection is set at 0. Types of treatment is indicated with different colors and durations of treatment is represented by the length of the line for each patient. II denotes suspension of treatment as a result of treatment-related adverse events. X denotes cessation of treatment due to progressive disease. AE, adverse events
Fig. 2
Fig. 2
Best Response of on-target lesions. Changes in the injectable lesions for each patient are shown as waterfall plot. CR, complete response. Cutaneous lesions are shown in blue and subcutaneous lesions are shown in red. CR, complete response
Fig. 3
Fig. 3
Change of tumor burden in on-target lesions. Change of tumor burden from baseline (before T-VEC injection) in injected lesions for each patient is shown as a function time measured in weeks. The time of T-VEC injection is set at 0. End of line indicates time of observation
Fig. 4
Fig. 4
Change of tumor burden in off-target lesions. Changes of tumor burden for two patients who had measurable uninjected lesions are shown as a function of time measured in weeks. The time of T-VEC treatment is set at 0. End of line indicates time of observation
Fig. 5
Fig. 5
Overall and Progression Free survival. (a) 12-month overall survival. (b) 12-month progression free survival. Data expressed as time since T-VEC injection (n = 10). Dotted line represents ± standard of error
Fig. 6
Fig. 6
Changes in circulating T cells. (a) Percentages of circulating CD4 and CD8 T cells in complete and partial responders responders before and after T-VEC plus pembrolizumab (b) CD4:CD8 ratios complete and partial responders responders before and after T-VEC plus pembrolizumab. (c) Percentages of PD1+ CD4 and CD8 T cells in complete and partial responders responders before and after T-VEC plus pembrolizumab
See this image and copyright information in PMC

References

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