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T-VEC for stage IIIB-IVM1a melanoma achieves high rates of complete and durable responses and is associated with tumor load: a clinical prediction model

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Abstract

Background

Talimogene laherparepvec (T-VEC) is a genetically modified herpes simplex type 1 virus and known as an effective oncolytic immunotherapy for injectable cutaneous, subcutaneous and nodal melanoma lesions in stage IIIB-IVM1a patients. This study set out to identify prognostic factors for achieving a complete response that can be used to optimize patient selection for T-VEC monotherapy.

Methods

Patients with stage IIIB-IVM1a melanoma, treated with T-VEC at the Netherlands Cancer Institute between 2016–12 and 2020–01 with a follow-up time > 6 months, were included. Data were collected on baseline characteristics, responses and adverse events (AEs). Uni- and multivariable analyses were conducted, and a prediction model was developed to identify prognostic factors associated with CR.

Results

A total of 93 patients were included with a median age of 69 years, median follow-up time was 16.6 months. As best response, 58 patients (62%) had a CR, and the overall response rate was 79%. The durable response rate (objective response lasting > 6 months) was 51%. Grade 1–2 AEs occurred in almost every patient. Tumor size, type of metastases, prior treatment with systemic therapy and stage (8Th AJCC) were independent prognostic factors for achieving CR. The prediction model includes the predictors tumor size, type of metastases and number of lesions.

Conclusions

This study shows that intralesional T-VEC monotherapy is able to achieve high complete and durable responses. The prediction model shows that use of T-VEC in patients with less tumor burden is associated with better outcomes, suggesting use earlier in the course of the disease.

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Data availability

Data and material presented in this study are available on request.

Abbreviations

AE:

Adverse event

AUC:

Area under the curve

AJCC:

American Joint Committee on Cancer

CR:

:Complete response

DRR:

Durable response rate

EMA:

European Medicines Agency

FDA:

Food and Drug Administration

HSV-1:

Herpes simplex type 1 virus

LDH:

Lactate dehydrogenase

ORR:

Overall response rate

OS:

Overall survival

PR:

Partial response

PFU:

Plaque-forming units

PET/CT:

Positron emission tomography/computed tomography

PD:

Progressive disease

PFS:

Progression-free survival

RFS:

Relapse-free survival

ROC:

Receiver operating characteristic

T-VEC:

Talimogene laherparepvec

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Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Departments of Surgical Oncology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, Plesmanlaan 121, Room U2.38, 1066 CX, Amsterdam, The Netherlands

    Emma H. A. Stahlie, Viola Franke, Michel W. J. M. Wouters, Yvonne M. Schrage, Winan J. van Houdt & Alexander C. J. van Akkooi

  2. Head and Neck Surgery and Oncology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Charlotte L. Zuur & Willem M. C. Klop

  3. Nuclear Medicine, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Bernies van der Hiel

  4. Pathology, Netherlands Cancer Institute-Antoni Van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands

    Bart A. Van de Wiel

Authors
  1. Emma H. A. Stahlie
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  2. Viola Franke
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  3. Charlotte L. Zuur
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  4. Willem M. C. Klop
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  6. Bart A. Van de Wiel
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  7. Michel W. J. M. Wouters
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  9. Winan J. van Houdt
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  10. Alexander C. J. van Akkooi
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Contributions

Conceptualization: ES, AvA; Methodology: ES, AvA; Formal analysis and investigation: ES; Writing—original draft preparation: ES; Writing—review and editing: ES, VF, CZ, WK, BvdH, BvdW, MW, YS, WvH; Funding acquisition: AvA; Resources: ES, VF, CZ, WK, BvdH, BvdW, MW, YS, WvH; Supervision: AvA.

Corresponding author

Correspondence to Alexander C. J. van Akkooi.

Ethics declarations

Conflict of interest

Winan van Houdt declares advisory board/consultancy agreement and research grant received from Amgen. Michel Wouters declares a research grant received from Novartis. Alexander van Akkooi declares advisory board/consultancy agreements for Bristol-Myers Squibb, Novartis, MSD – Merck, Merck – Pfizer, 4SC and Amgen and a research grant received from Bristol-Myers Squibb, Novartis and Amgen. All other others have no relevant financial or non-financial interests to disclose.

Consent to participate

No identifiable patient information has been published warranting individual consent from patients. The requirement for individual patient informed consent for the purpose of data collection and publication was waived as per the regulations covered under the respective institutional IRBs.

Ethical approval

The study was performed with the approval of the Institutional Review Board (IRB) Netherlands Cancer Institute – Antoni van Leeuwenhoek and in accordance with the declaration of Helskini.

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Stahlie, E.H.A., Franke, V., Zuur, C.L. et al. T-VEC for stage IIIB-IVM1a melanoma achieves high rates of complete and durable responses and is associated with tumor load: a clinical prediction model. Cancer Immunol Immunother 70, 2291–2300 (2021). https://doi.org/10.1007/s00262-020-02839-7

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  • DOI: https://doi.org/10.1007/s00262-020-02839-7

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