Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

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

doi:10.1016/j.ejca.2023.03.009

Response to checkpoint inhibition and targeted therapy in melanoma patients with concurrent haematological malignancies

Eur J Cancer. 2023 Jun:186:27-37. doi: 10.1016/j.ejca.2023.03.009. Epub 2023 Mar 16.

Authors

Olivier J Van Not¹, Alfons J M van den Eertwegh², John B Haanen³, Rozemarijn S van Rijn⁴, Maureen J B Aarts⁵, Franchette W P J van den Berkmortel⁶, Christian U Blank⁷, Marye J Boers-Sonderen⁸, Mick J M van Eijs⁹, Jan-Willem B de Groot¹⁰, Geke A P Hospers¹¹, Ellen Kapiteijn¹², Melissa de Meza¹³, Djura Piersma¹⁴, Marion Stevense-den Boer¹⁵, Astrid A M van der Veldt¹⁶, Gerard Vreugdenhil¹⁷, Michel W J M Wouters¹³, Karijn P M Suijkerbuijk¹⁸, Willeke A M Blokx¹⁹

Affiliations

¹ Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, The Netherlands; Department of Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht 3584CX, The Netherlands. Electronic address: O.J.vanNot@umcutrecht.nl.
² Department of Medical Oncology, Amsterdam UMC, VU University Medical Center, Cancer Center Amsterdam, De Boelelaan 1118, Amsterdam 1081HZ, The Netherlands.
³ Department of Molecular Oncology & Immunology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, The Netherlands.
⁴ Department of Internal Medicine, Medical Centre Leeuwarden, Henri Dunantweg 2, Leeuwarden 8934AD, The Netherlands.
⁵ Department of Medical Oncology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, P. Debyelaan 25, Maastricht 6229 HX, The Netherlands.
⁶ Department of Medical Oncology, Zuyderland Medical Centre Sittard, Dr. H. van der Hoffplein 1, Sittard-Geleen 6162BG, The Netherlands.
⁷ 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.
⁸ Department of Medical Oncology, Radboud University Medical Centre, Geert Grooteplein Zuid 10, Nijmegen 6525GA, The Netherlands.
⁹ Department of Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht 3584CX, The Netherlands; Center for Translational Immunology, University Medical Centre Utrecht, Lundlaan 6, Utrecht 3584EA, The Netherlands.
¹⁰ Isala Oncology Center, Isala, Dokter van Heesweg 2, Zwolle 8025AB, The Netherlands.
¹¹ Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, Groningen 9713GZ, The Netherlands.
¹² Department of Medical Oncology, Leiden University Medical Centre, Albinusdreef 2, Leiden 2333ZA, The Netherlands.
¹³ Dutch Institute for Clinical Auditing, Rijnsburgerweg 10, Leiden 2333AA, The Netherlands; Department of Biomedical Data Sciences, Leiden University Medical Centre, Einthovenweg 20, Leiden 2333ZC, The Netherlands; Department of Surgical Oncology, Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam 1066CX, The Netherlands.
¹⁴ Department of Internal Medicine, Medisch Spectrum Twente, Koningsplein 1, Enschede 7512KZ, 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 Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht 3584CX, The Netherlands.
¹⁹ Department of Pathology, University Medical Centre Utrecht, Heidelberglaan 100, Utrecht 3584CX, The Netherlands.

PMID: 37023588
DOI: 10.1016/j.ejca.2023.03.009

Abstract

Background: Patients diagnosed with haematologic malignancies (HMs) have a higher risk of developing subsequent solid tumours, such as melanoma. Patients with HM were mostly excluded from clinical trials but potentially derive less benefit from immune checkpoint inhibitors (ICIs) due to disease- or treatment-related T- or B-cell dysfunction.

Methods: All advanced melanoma patients treated with anti-PD-1-based treatment or targeted therapy between 2015 and 2021 were included from the prospective nationwide Dutch Melanoma Treatment Registry. Progression-free survival (PFS) and melanoma-specific survival (MSS) were analysed for patients with HM (HM+) and without HM (HM-). A cox model was used to account for confounders associated with PFS and MSS.

Results: In total, 4638 advanced melanoma patients received first-line anti-PD-1 monotherapy (n = 1763), ipilimumab-nivolumab (n = 800), or BRAF(/MEK) inhibitors (n = 2075). Concurrent HMs were present for 46 anti-PD1-treated patients, 11 ipilimumab-nivolumab-treated patients and 43 BRAF(/MEK)-inhibitor-treated patients. In anti-PD-1-treated patients, the median PFS was 2.8 months for HM+ and 9.9 months for HM- (p = 0.01). MSS was 41.2 months for HM+ and 58.1 months for HM- (p = 0.00086). In multivariable analysis, the presence of an HM was significantly associated with higher risk of melanoma progression (HR_adj 1.62; 95% confidence interval [95% CI] 1.15-2.29; p = 0.006) and melanoma-related death (HR_adj 1.74; 95% CI 1.09-2.78; p = 0.020). Median PFS and MSS for first-line BRAF(/MEK-) inhibitor-treated HM+ and HM- patients were not significantly different.

Conclusions: Patients with HM and advanced melanoma show significantly worse melanoma-related outcomes when treated with ICI, but not targeted therapy, compared to patients without HM. Clinicians should be aware of potentially altered effectiveness of ICI in patients with active HM.

Keywords: Haematologic malignancy; Immune checkpoint inhibitors; Melanoma; Response; Survival.

Publication types

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

MeSH terms

Hematologic Neoplasms*
Humans
Ipilimumab
Melanoma* / pathology
Mitogen-Activated Protein Kinase Kinases
Nivolumab / therapeutic use
Prospective Studies
Proto-Oncogene Proteins B-raf
Retrospective Studies

Substances

Nivolumab
Ipilimumab
Proto-Oncogene Proteins B-raf
Mitogen-Activated Protein Kinase Kinases