Hyperprogressive disease rarely occurs during checkpoint inhibitor treatment for advanced melanoma
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RESEARCH REPORT
Hyperprogressive disease rarely occurs during checkpoint inhibitor treatment for advanced melanoma M. Schuiveling1 · E. H. J. Tonk1 · R. J. Verheijden1 · K. P. M. Suijkerbuijk1 Received: 15 June 2020 / Accepted: 31 August 2020 © The Author(s) 2020
Abstract Introduction Hyperprogression, characterized by a rapid acceleration in tumor growth, is a novel pattern of progression recently described in patients treated with immune checkpoint inhibitors. This study aims to assess the incidence of hyperprogression in patients with advanced melanoma treated with checkpoint inhibitors. Methods Clinical and radiological findings of all advanced melanoma patients who started checkpoint inhibitors between January 2013 and March 2019 in a tertiary academic center in the Netherlands were analyzed. Change in tumor burden was calculated by assessing volumetric tumor growth using the criteria as defined by immune Response Evaluation Criteria in Solid Tumors version 1.1. Hyperprogression was defined as a time to treatment failure less than 2 months with doubling of tumor burden and a twofold increase in tumor growth rate during treatment. Possible hyperprogression was defined as the presence of the first two criteria in the absence of a pre-baseline scan. Results Out of 206 treatment episodes in 168 patients, 75 were evaluable for hyperprogression and 87 for possible hyperprogression. Hyperprogression was observed in one patient (1.3%) and possible hyperprogression was observed in one patient (1.1%). Conclusion Hyperprogression is rare in melanoma patients treated with immune checkpoint inhibitors. Our data question if hyperprogression really is a biological entity in metastatic melanoma. Keywords Melanoma · Immune checkpoint inhibitors · Hyperprogression · Hyperprogressive disease · Anti-PD1 Abbreviations AACR American Association of Cancer Research CRP C-reactive protein CTLA4 Cytotoxic T-lymphocyte-associated protein 4 CT-scan Computerized tomography scan ICI Immune checkpoint inhibitor iRECIST Immune Response Evaluation Criteria in Solid Tumors LDH Lactate dehydrogenase MRI-scan Magnetic resonance imaging scan PD1 Programmed cell death 1 TGR Tumor growth rate TTF Time to treatment failure
* K. P. M. Suijkerbuijk [email protected] 1
Department of Medical Oncology, University Medical Center Utrecht Cancer Center, Utrecht, The Netherlands
Introduction Over the last decade, treatment of metastatic melanoma has profoundly improved due to the introduction of immune checkpoint inhibitors (ICI) against cytotoxic T-lymphocyteassociated protein 4 (CTLA4) and programmed cell death 1 (PD1). Anti-CTLA4 re-induces the T-cell activation by antigen presenting cells whereas anti-PD1 inhibits the interaction leading to tumor escape between T-cells and tumor cells in the tumor microenvironment [1, 2]. The introduction of ICI led to the observation of novel tumor treatment responses, such as a delayed response or pseudoprogression [3]. Moreover, recent studies reported hyperprogression, an unprece
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