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Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-Transit Disease

  • Melanomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 12 December 2014

ABSTRACT

Purpose

Melanoma patients with in-transit disease have a high mortality rate despite various treatment strategies. The aim of this study was to validate the role of intralesional interleukin (IL)-2, to understand its mechanism of action, and to better understand factors that may influence its response.

Methods

We retrospectively collected the clinicopathological data of 31 consecutive patients who presented to a tertiary care cancer center for treatment of in-transit melanoma with intralesional IL-2. Kaplan–Meier survival curves and multivariable Cox regression analysis were performed. Immunohistochemistry (IHC) was used to better understand the immune response to localized IL-2 therapy. Targeted next-generation sequencing was performed to genomically characterize the tumors.

Results

Ten patients (10/31, 32 %) achieved a pathologic complete response (pCR), 17/21 (55 %) had a partial response, and 4/21 (19 %) had progressive disease on treatment. pCR to IL-2 therapy was associated with overall survival (log-rank p = 0.004) and improved progression-free survival (PFS) [adjusted hazard ratio (HR) 0.11; 95 % CI 0.02–0.47; p = 0.003). A higher CD8+ T cell infiltrate was identified in in-transit lesions with a pCR compared with the other lesions (mean IHC score 3.78 vs. 2.61; p = 0.01). Patients with an elevated CD8+ infiltrate demonstrated an improved PFS (unadjusted HR 0.08; 95 % CI 0.01–0.52; p = 0.008).

Conclusions

Thirty-two percent of patients achieved pCR with intralesional IL-2 therapy and had a significantly improved PFS compared with the rest of the cohort, which may be explained by a systemic CD8+ T-cell response.

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Acknowledgment

The authors would like to thank the institutions across Ontario who helped provide paraffin-embedded blocks for this study, including University Health Network, Barrie Royal Victoria Hospital, Muskoka Algonquin Healthcare, Headwaters Health, Orillia Soldier’s Memorial Hospital, West Parry Sound Health Centre, Lifelabs, Gamma Dynacare, Windsor Regional Hospital, Ross Memorial Hospital, Peterborough Regional Health Centre, London Health Sciences Centre, St. Mary’s General Hospital, Kitchener, Kingston General Hospital, and Grand River Hospital. This study was supported by the William S. Fenwick Fellowship and the Joseph M. West Family Memorial Fund from the 2012 Postgraduate Medical Research Award, awarded to Saima Hassan, University of Toronto; Melanoma Site Group from Sunnybrook Health Sciences Centre, awarded to Teresa Petrella; and a Research Grant from Pathology Associates from the University Health Network, awarded to Danny Ghazarian.

Disclosure

Novartis provided interleukin-2 to patients free of charge as part of a compassionate release program. Novartis was not involved in funding this research study. Teresa Petrella and an immediate family member received honoraria from Novartis, Roche, BMS, Merck, GSK, Amgen, AstraZeneca, Electa, Janssen, Paladin, and Sanofi; they served as a consultant or in an advisory role for Novartis, Roche, BMS, Merck, GSK, Amgen, Astellas, Janssen, and Sanofi. An immediate family member of Teresa Petrella was paid to speak at a speaker’s bureau from Amgen, and has received research funding from Sanofi and Paladin. The University Health Network, Toronto, ON, Canada, where Suzanne Kamel-Reid is an employee, receives research funding from Novartis. Saima Hassan, Tong Zhang, Francesco Nordio, Andrea Baccarelli, Shachar Sade, Karen Naert, Ayman Al Habeeb, Danny Ghazarian, and Frances Wright have nothing to disclose.

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Authors and Affiliations

  1. Division of Surgical Oncology, Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, ON, Canada

    Saima Hassan MD, PhD, FRCSC & Frances C. Wright MD, MEd, FRCSC

  2. Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA

    Saima Hassan MD, PhD, FRCSC

  3. Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Teresa M. Petrella MD, MSc, FRCPC

  4. Department of Pathology, University Health Network, Toronto, ON, Canada

    Tong Zhang MSc, Suzanne Kamel-Reid BA, MA, PhD, FACMG, Karen Naert MD, FRCPC, Ayman Al Habeeb MBBS, FRCPC & Danny Ghazarian MB ChB, PhD, FRCPC, FCAP

  5. Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

    Francesco Nordio PhD

  6. Department of Environmental Health and Epidemiology, Harvard School of Public Health, Boston, MA, USA

    Andrea Baccarelli MD, PhD

  7. Department of Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Shachar Sade MD, MSc, FRCPC

Authors
  1. Saima Hassan MD, PhD, FRCSC
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  2. Teresa M. Petrella MD, MSc, FRCPC
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  3. Tong Zhang MSc
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  11. Frances C. Wright MD, MEd, FRCSC
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Corresponding author

Correspondence to Frances C. Wright MD, MEd, FRCSC.

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Hassan, S., Petrella, T.M., Zhang, T. et al. Pathologic Complete Response to Intralesional Interleukin-2 Therapy Associated with Improved Survival in Melanoma Patients with In-Transit Disease. Ann Surg Oncol 22, 1950–1958 (2015). https://doi.org/10.1245/s10434-014-4199-z

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  • DOI: https://doi.org/10.1245/s10434-014-4199-z

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