Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Olivier J van Not; Melissa M de Meza; Alfons J M van den Eertwegh; John B Haanen; Christian U Blank; Maureen J B Aarts; Franchette W P J van den Berkmortel; Jesper van Breeschoten; Jan-Willem B de Groot; Geke A P Hospers; Rawa K Ismail; Ellen Kapiteijn; Djura Piersma; Roos S van Rijn; Marion A M Stevense-den Boer; Astrid A M van der Veldt; Gerard Vreugdenhil; Han J Bonenkamp; Marye J Boers-Sonderen; Willeke A M Blokx; Michel W J M Wouters; Karijn P M Suijkerbuijk

doi:10.1016/j.ejca.2022.02.026

Response to immune checkpoint inhibitors in acral melanoma: A nationwide cohort study

Eur J Cancer. 2022 May:167:70-80. doi: 10.1016/j.ejca.2022.02.026. Epub 2022 Apr 5.

Authors

Olivier J van Not¹, Melissa M de Meza², Alfons J M van den Eertwegh³, John B Haanen⁴, Christian U Blank⁵, Maureen J B Aarts⁶, Franchette W P J van den Berkmortel⁷, Jesper van Breeschoten⁸, Jan-Willem B de Groot⁹, Geke A P Hospers¹⁰, Rawa K Ismail¹¹, Ellen Kapiteijn¹², Djura Piersma¹³, Roos S van Rijn¹⁴, Marion A M Stevense-den Boer¹⁵, Astrid A M van der Veldt¹⁶, Gerard Vreugdenhil¹⁷, Han J Bonenkamp¹⁸, Marye J Boers-Sonderen¹⁹, Willeke A M Blokx²⁰, Michel W J M Wouters², Karijn P M Suijkerbuijk²¹

Affiliations

¹ Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, the Netherlands; Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584CX, the Netherlands. Electronic address: O.J.vanNot@umcutrecht.nl.
² Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, the Netherlands; Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Centre, Einthovenweg 20, Leiden 2333ZC, the Netherlands.
³ Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, Amsterdam 1081HZ, the Netherlands.
⁴ Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the Netherlands.
⁵ Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the Netherlands; Department of Medical Oncology & Immunology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, the Netherlands.
⁶ Department of Medical Oncology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, P. Debyelaan 25, Maastricht 6229 HX, the Netherlands.
⁷ Department of Medical Oncology, Zuyderland Medical Centre Sittard, Dr. H. van der Hoffplein 1, Sittard-Geleen 6162BG, the Netherlands.
⁸ Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, the Netherlands; Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, Amsterdam 1081HZ, the Netherlands.
⁹ Isala Oncology Center, Isala, Dokter van Heesweg 2, Zwolle 8025AB, the Netherlands.
¹⁰ Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen 9713GZ, the Netherlands.
¹¹ Scientific Bureau, Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, the Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht, the Netherlands.
¹² Department of Medical Oncology, Leiden University Medical Centre, Albinusdreef 2, Leiden 2333ZA, the Netherlands.
¹³ Department of Internal Medicine, Medisch Spectrum Twente, Koningsplein 1, Enschede 7512KZ, the Netherlands.
¹⁴ Department of Internal Medicine, Medical Centre Leeuwarden, Henri Dunantweg 2, Leeuwarden 8934AD, the Netherlands.
¹⁵ Department of Internal Medicine, Amphia Hospital, Molengracht 21, Breda 4818CK, the Netherlands.
¹⁶ Department of Medical Oncology and Radiology & Nuclear Medicine, Erasmus Medical Centre, 's-Gravendijkwal 230, Rotterdam 3015CE, the Netherlands.
¹⁷ Department of Internal Medicine, Maxima Medical Centre, De Run 4600, Eindhoven 5504DB, the Netherlands.
¹⁸ Department of Surgery, Radboud University Medical Center, Geert Grooteplein Zuid 10, Nijmegen 6525GA, the Netherlands.
¹⁹ Department of Medical Oncology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, Nijmegen 6525GA, the Netherlands.
²⁰ Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584CX, the Netherlands.
²¹ Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3584CX, the Netherlands.

PMID: 35395553
DOI: 10.1016/j.ejca.2022.02.026

Abstract

Background: Recent reports suggest the limited efficacy of immune checkpoints inhibitors in advanced acral melanoma (AM). This study aims to investigate the clinical outcomes of immune checkpoint inhibitors in patients with stage III and IV AM and compare them to cutaneous melanoma (CM).

Methods: We included patients with advanced AM and CM treated with first-line anti-programmed cell death (PD)-1 monotherapy or ipilimumab-nivolumab registered in the prospective nationwide Dutch Melanoma Treatment Registry. Objective response rates, progression-free survival (PFS) and overall survival (OS) were calculated. A Cox proportional hazard model was used to assess the prognostic factors with PFS and OS.

Results: In total, 2058 patients (88 AM and 1970 CM) with advanced melanoma were included. First-line objective response rates were 34% for AM versus 54% for CM in the advanced anti-PD-1 cohort and 33% for AM versus 53% for CM in the advanced ipilimumab-nivolumab cohort. The Median PFS was significantly shorter for anti-PD-1 treated AM patients (3.1 months; 95%CI: 2.8-5.6) than patients with CM (10.1 months; 95%CI: 8.5-12.2) (P < 0.001). In patients with advanced melanoma, AM was significantly associated with a higher risk of progression (HRadj 1.63; 95%CI: 1.26-2.11; P < 0.001) and death (HRadj 1.54; 95%CI: 1.15-2.06; P = 0.004) than CM.

Conclusions: This study shows lower effectiveness of anti-PD -1 monotherapy and ipilimumab-nivolumab in AM, with lower response rates, PFS and OS than CM. This group of patients should be prioritised in the development of alternative treatment strategies.

Keywords: Immune checkpoint inhibitors; Immunotherapy; Melanoma; Response; Survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cohort Studies
Humans
Immune Checkpoint Inhibitors* / therapeutic use
Ipilimumab / therapeutic use
Melanoma / mortality
Melanoma, Cutaneous Malignant
Nivolumab / adverse effects
Prospective Studies
Skin Neoplasms* / drug therapy
Skin Neoplasms* / immunology

Substances

Immune Checkpoint Inhibitors
Ipilimumab
Nivolumab