Advanced stage melanoma during pregnancy: recommendations from a retrospective, multicentre, registry-based study

Jessica S W Borgers¹, Douglas B Johnson², Elisabeth Livingstone^{3

4

5}, Dirk Schadendorf^{3

4

5}, Elizabeth I Buchbinder⁶, Lauren E Haydu⁷, Laura Gohil⁸, William A Robinson⁹, Inderjit Mehmi¹⁰, Omid Hamid¹⁰, Michelle Ferreira¹¹, April K S Salama¹¹, Florentia Dimitriou^{12

8}, Matteo S Carlino¹³, Georgina V Long^{13

14

15

16}, Paolo A Ascierto¹⁷, Ester Simeone¹⁸, Yana G Najjar¹⁹, Geke A P Hospers²⁰, Jacob Choi²¹, Sunandana Chandra²¹, Jeffrey D Wayne²², Carlos I R García²³, Wen Xu^{24

25}, Céleste Lebbé²⁶, Laetitia Da-Meda²⁶, Victoria Atkinson²⁷, Meredith Mckean²⁸, Andrea Forschner²⁹, Elliot A Asare³⁰, Antonios Daletzakis³¹, Jolyn S Taylor³², Frédéric Amant^{33

34}, Katy K Tsai³⁵, Zeynep Eroglu³⁶, John B A G Haanen^{1

37

38}, Isabella C Glitza de Oliva³⁹

Affiliations

¹ Department of Medical Oncology, Netherlands Cancer Institute, the Netherlands.
² Department of Medicine, Vanderbilt University Medical Center, TN, USA.
³ Department of Dermatology, University Hospital Essen, Germany.
⁴ The German Cancer Consortium, Campus Essen, Germany.
⁵ National Center for Tumor Diseases (NCT-West), Campus Essen & Research Alliance Ruhr, Research Center One Health, Campus Essen, Germany.
⁶ Department of Medical Oncology, Dana Farber Cancer Institute, MA, USA.
⁷ Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL, USA.
⁸ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Center for Rare Melanomas, CU Anschutz Medical Center, CO, USA.
¹⁰ Department of Hematology Oncology, The Angeles Clinic and Research Institute, Cedar Sinai Affiliate, CA, USA.
¹¹ Department of Medicine, Duke University, NC, USA.
¹² Department of Dermatology, University Hospital of Zurich, Switzerland.
¹³ Department of Medical Oncology, Melanoma Institute Australia, The University of Sydney, Australia.
¹⁴ Faculty of Medicine & Health, The University of Sydney, Australia.
¹⁵ Charles Perkins Centre, The University of Sydney, Australia.
¹⁶ Royal North Shore & Mater Hospitals, Australia.
¹⁷ Department of Melanoma, Istituto Nazionale Tumori Fondazione G, Pascale, Italy.
¹⁸ Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori Fondazione G, Pascale, Italy.
¹⁹ Department of Hematology/Oncology, University of Pittsburgh Medical Center, PA, USA.
²⁰ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, the Netherlands.
²¹ Department of Medicine, Division of Hematology and Oncology, Northwestern University, IL, USA.
²² Division of Surgical Oncology, Northwestern Memorial Hospital, IL, USA.
²³ Department of Medical Oncology, Centro de Investigación Clínica Bradford Hill, Chile.
²⁴ Department of Medical Oncology, Princess Alexandra Hospital, Brisbane, Australia.
²⁵ University of Queensland, Brisbane, Australia.
²⁶ Department of Dermatology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, France.
²⁷ Department of Medical Oncology, Princess Alexandra Hospital, Australia.
²⁸ Sarah Cannon Research Institute, Tennessee Oncology, TN, USA.
²⁹ Department of Dermatology, Eberhard Karls University of Tuebingen, Germany.
³⁰ Department of Surgery, University of Utah, Huntsman Cancer Institute, UT, USA.
³¹ Department of Biometrics, Netherlands Cancer Institute, the Netherlands.
³² Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³³ Department of Gynecology, Netherlands Cancer Institute, the Netherlands.
³⁴ Division of Gynecologic Oncology, UZ Leuven, Belgium.
³⁵ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, USA.
³⁶ Department of Cutaneous Oncology, Moffitt Cancer Center, FL, USA.
³⁷ Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
³⁸ Melanoma Clinic, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
³⁹ Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 41127564
PMCID: PMC12538904
DOI: 10.1016/j.eclinm.2025.103501

Advanced stage melanoma during pregnancy: recommendations from a retrospective, multicentre, registry-based study

Jessica S W Borgers et al. EClinicalMedicine. 2025.

. 2025 Oct 7:89:103501.

doi: 10.1016/j.eclinm.2025.103501. eCollection 2025 Nov.

Authors

Affiliations

¹ Department of Medical Oncology, Netherlands Cancer Institute, the Netherlands.
² Department of Medicine, Vanderbilt University Medical Center, TN, USA.
³ Department of Dermatology, University Hospital Essen, Germany.
⁴ The German Cancer Consortium, Campus Essen, Germany.
⁵ National Center for Tumor Diseases (NCT-West), Campus Essen & Research Alliance Ruhr, Research Center One Health, Campus Essen, Germany.
⁶ Department of Medical Oncology, Dana Farber Cancer Institute, MA, USA.
⁷ Department of Quantitative Health Sciences, Division of Clinical Trials and Biostatistics, Mayo Clinic, Jacksonville, FL, USA.
⁸ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁹ Center for Rare Melanomas, CU Anschutz Medical Center, CO, USA.
¹⁰ Department of Hematology Oncology, The Angeles Clinic and Research Institute, Cedar Sinai Affiliate, CA, USA.
¹¹ Department of Medicine, Duke University, NC, USA.
¹² Department of Dermatology, University Hospital of Zurich, Switzerland.
¹³ Department of Medical Oncology, Melanoma Institute Australia, The University of Sydney, Australia.
¹⁴ Faculty of Medicine & Health, The University of Sydney, Australia.
¹⁵ Charles Perkins Centre, The University of Sydney, Australia.
¹⁶ Royal North Shore & Mater Hospitals, Australia.
¹⁷ Department of Melanoma, Istituto Nazionale Tumori Fondazione G, Pascale, Italy.
¹⁸ Cancer Immunotherapy and Development Therapeutics Unit, Istituto Nazionale Tumori Fondazione G, Pascale, Italy.
¹⁹ Department of Hematology/Oncology, University of Pittsburgh Medical Center, PA, USA.
²⁰ Department of Medical Oncology, University Medical Center Groningen, University of Groningen, the Netherlands.
²¹ Department of Medicine, Division of Hematology and Oncology, Northwestern University, IL, USA.
²² Division of Surgical Oncology, Northwestern Memorial Hospital, IL, USA.
²³ Department of Medical Oncology, Centro de Investigación Clínica Bradford Hill, Chile.
²⁴ Department of Medical Oncology, Princess Alexandra Hospital, Brisbane, Australia.
²⁵ University of Queensland, Brisbane, Australia.
²⁶ Department of Dermatology, Hôpital Saint Louis, Assistance Publique-Hôpitaux de Paris, France.
²⁷ Department of Medical Oncology, Princess Alexandra Hospital, Australia.
²⁸ Sarah Cannon Research Institute, Tennessee Oncology, TN, USA.
²⁹ Department of Dermatology, Eberhard Karls University of Tuebingen, Germany.
³⁰ Department of Surgery, University of Utah, Huntsman Cancer Institute, UT, USA.
³¹ Department of Biometrics, Netherlands Cancer Institute, the Netherlands.
³² Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
³³ Department of Gynecology, Netherlands Cancer Institute, the Netherlands.
³⁴ Division of Gynecologic Oncology, UZ Leuven, Belgium.
³⁵ Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, USA.
³⁶ Department of Cutaneous Oncology, Moffitt Cancer Center, FL, USA.
³⁷ Department of Medical Oncology, Leiden University Medical Center, Leiden, the Netherlands.
³⁸ Melanoma Clinic, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
³⁹ Department of Melanoma Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

PMID: 41127564
PMCID: PMC12538904
DOI: 10.1016/j.eclinm.2025.103501

Abstract

Background: Diagnosis and treatment of advanced melanoma during pregnancy represents a major challenge, with scarce data on outcome or management available. Therefore, the Melanoma Pregnancy Taskforce collected real-world data to understand the current management approaches.

Methods: This retrospective, multicenter database included patients who were either diagnosed with advanced melanoma (newly diagnosed or recurrent) during pregnancy (group 1) or conceived while on systemic treatment (group 2) between 01/01/2011 and 07/31/2024. Information regarding patient, primary tumor and advanced melanoma characteristics, intervention or treatment during pregnancy, and outcomes of mother and fetus were collected using a standardized, de-identified form.

Findings: 72 women from seven countries were identified. In group 1 (n = 63), nine pregnancies were terminated, and two miscarried. Median gestational age of live births was 34 weeks (IQR 32-37). Nine patients initiated systemic treatment during pregnancy; 56 (85%) of 66 switched or initiated new treatment after delivery. 5-year overall survival was 53% (95% CI 39-71), with median follow-up of 27 months (IQR 1.0-4.8 years). In group 2 (n = 10), four pregnancies were terminated, one miscarried. Of the six live births, median gestational age was 33 weeks (IQR 32-NR). Seven (63%) of nine initiated new or continued treatment after delivery. 5-year overall survival was 71% (95% CI 51-100), with median follow-up of 42 months (IQR 2.5-4.5 years). One neonate born at 26 weeks died after three days and one had a fatal congenital malformation. One child with third trimester vemurafenib-exposure had cardiac malformations, and two neonates experienced toxicity after in utero immunotherapy exposure. No children developed melanoma, despite five placentas with melanoma involvement.

Interpretation: Here, we present the data from the largest contemporary dataset of outcomes of women diagnosed with advanced stage melanoma during pregnancy and provide recommendations for the diagnosis and management of advanced melanoma during pregnancy.

Funding: Not applicable.

Keywords: Guidelines; Immunotherapy; Melanoma; Outcomes; Pregnancy; Treatment.

PubMed Disclaimer

Conflict of interest statement

DBJ served on advisory boards or as a consultant for AstraZeneca, Bristol Myers Squibb, The Jackson Laboratory, Mallinckrodt, Merck, Mosaic ImmunoEngineering, Novartis, Pfizer, and Teiko, and has received research funding from Bristol Myers Squibb and Incyte. EL has consulting/advisory roles for Bristol Myers and Squibb, Merck Sharp & Dohme, Novartis, Pierre-Fabre, Sunpharma, Takeda; received honoraria payments from Bristol Myers and Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sunpharma, and Takeda; and travel support from Pierre-Fabre, and Sunpharma. DS holds consulting/advisory roles for Astra-Zeneca, Daiichi Sankyo, Erasca, Haystack, Anaevon, Immatics, Immunocore, InFlarX, Innovent, Merck-Serono, Nektar, Neracare, NoviGenix, PamGene, Philogen, Pfizer, Regeneron, BioNTech, Replimune, Roche, Sanofi, Seagen, UltimoVacs, Bristol Myers and Squibb, Merck Sharp & Dohme, Novartis, Pierre-Fabre, and Sun Pharma; received honoraria from Bristol Myers and Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Sun Pharmal and received travel support from Pierre-Fabre; and received institutional research funding from Bristol Myers and Squibb, Merck Sharp & Dohme, Novartis, Amgen, Roche and Pfizer. EIB reports personal fees from Obsidian, Anaveon, Merck, Werewolf, Iovance, and Sanofi outside the submitted work. IM reported consulting fees for Guidepoint; received honoraria from Immunocore and BMS; participated on an advisory board from Mural Oncology; and own stock of Ideaya, Delcath, Immunocore and Iovance. OH reports consulting fees, received travel support and participated on advisory boards for Alkermes, Amgen, Bactonix, BeiGene, BioAtla, Bristol Myers Squibb, Eisai, Roche Genentech, Georgiamune, GigaGen, Grit Bio, GSK, Idera, Immunocore, Incyte, Instil Bio, IO Bio, Iovance, Janssen, KSQ, Merck, Moderna, NGM Bio, Novartis, Obsidian, Pfizer, Regeneron, Sanofi, Seattle Genetics, Tempus, Vial, and Zelluna outside the submitted work. MF received grant and travel support from the NIH (T32: T32CA009071), unrelated to the current work. AKSS reported receiving grants from Ascentage, Bristol Myers Squibb, Ideaya, Immunocore, Merck, Olatec Therapeutics, Regeneron, Replimune, and Seagen (paid to institution), and serving on the scientific advisory boards of Bristol Myers Squibb, Regeneron, Pfizer, Novartis, and Iovance outside the submitted work. MSC received consulting fees from Amgen, BMS, Eisai, Ideaya, MSH, Nektar, Novartis, Oncosec, Pierre-Fabre, Qbiotics, Regeneron, Roche, Merck, and Sanofi; and received honoraria from BMS, MSD, and Novartis. GVL reports personal fees from Agenus Inc, Amgen Inc, Array BioPharma, AstraZeneca, Bayer Healthcare, BioNTech, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion Biotech, GI Innovation, Hexal AG, Highlight Therapeutics, Immunocore, Innovent, IO Biotech, Iovance, MSD, Novartis, PHMR Limited, Pierre Fabre, Regeneron, Scancell, and SkylineDX outside the submitted work. PAA holds consultant/advisory role for Bristol Myers Squibb, Roche-Genentech, Merck Sharp & Dohme, Novartis, Merck Serono, Pierre-Fabre, Sun Pharma, Sanofi, Sandoz, Immunocore, Italfarmaco, Boehringer-Ingelheim, Regeneron, Pfizer, Nouscom, Medicenna, Bio-Al Health, ValoTX, Replimune, Bayer, Erasca, Philogen, Biontech, and Anaveon; received institutional research funding from Bristol Myers Squibb, Roche-Genentech, Pfizer, Sanofi; and travel support from Pfizer, Bio-Al Health, Replimune, Merck Sharp & Dohme, Pierre Fabre, and Philogen. YGN received funding from Merch, Pfizer, BMS, and replimune (paid to institution); consunting fees from Merck, Pfizer, Novartis, BMS, Immunocore, InverVenn Bio, Replimune, and Therakos; honoraria from Immunocore, and Pfizer; travel support from Pfizer; and participated on a advisory board for Pfizer. GAPH received grant support from Seerave and BMS (paid to institution); and consulting fees from BMS, Roche, MSD, Novartis, Sanofi, and Pierre Fabre (paid to institution). SC received travel support from COOG; and participated on an advisory board for Celltrion. CIRG participated on advisory boards from BMS, Pfizer, and Sanofi; received payment or honoraria from BMS, MSD, Roche, Pfizer, Astrazenica, and Knight. WX received consulting fees from Merck, MSD, BMS, and Novartis; received honoraria from Merck, MSD, BMS, and AZD; received travel support from Merck, MSD, BMS, AZD, and Daiichi-Sankyo. CL is a consultant advisor for Bristol Myers and Squibb, Merck Sharp & Dohme, Novartis, Roche, Pierre-Fabre, and Immuncore; received travel support from PFO; and research funding from Bristol Myers and Squibb PFO. VA received consulting fees and participated on advisory boards for BMS, and MSD; speaker fees from BMS, MSD, and Novaritis; and travel support from Pierre Fabre. MM received funding from Aadi Biosciences, Alpine Immune Sciences, Arcus Biosciences, Arvinas, Ascentage Pharma Group, ASCO, Astellas, Aulos Bioscience, Bayer, Bicycle Therapeutics, BioMed Valley Discoveries, BioNTech, Boehringer Ingelheim, Bristol-Myers Squibb, C4 Therapeutics, Daiichi Sankyo, Dragonfly Therapeutics, EMD Serono, Epizyme, Erasca, Exelixis, Foghorn Therapeutics, G1 Therapeutics, Genentech/Roche, Gilead Sciences, GlaxoSmithKline, IconoVir Bio, IDEAYA Biosciences, Ikena Oncology, ImmVira Pharma, Infinity Pharmaceuticals, Jacobio Pharmaceuticals, Jazz Pharmaceutical, Kechow Pharma, Kezar Life Sciences, Kinnate BioPharma, Krystal Biotech, MedImmune, Mereo BioPharma, Metabomed, Moderna, NBE Therapeutics, Nektar, Novartis, NucMito Pharmaceuticals, OncoC4, Oncorus, OnKure, PACT Pharma, Pfizer, Plexxikon, Poseida, Prelude Therapeutics, Pyramid Biosciences, Regeneron, Remix Therapeutics, Sapience Therapeutics, Scholar Rock, Seattle Genetics, Synthrox, Takeda Pharmaceuticals, Teneobio, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, TopAlliance Biosciences, and Xilio (all paid to institution); and received consulting fees from Abbvie, Bristol-Myers Squibb, Castle Biosciences, Daiichi Sankyo, Ideaya Biosciences, IQVIA, Merck, Moderna, Pfizer, Pierre Fabre, Regeneron, and Revolution Medicine (all paid to institution). AF served as a consultant to Novartis, MSD, BMS, Pierre-Fabre and Immunocore; received travel support from Novartis, BMS, Pierre-Fabre, and received speaker fees from Novartis, BMS and MSD and reports institutional research grants from BMS Stiftung Immunonkologie, outside the submitted work. KKT received funding from ABM Therapeutics, AstraZeneca, and BioAtla (paid to institution); has royalties from BMS, Genetech, and Gerogiamune (paid to institution); received consulting fees from Ideya, Innovent, and OnKure (paid to institution); honoraria from Pfizer, Regeneron, and Replimune (paid to institution); and participated on an advisory board for BMS. ZE received grants from Pfizer, and Boehringer Ingelheim; participated on advisory boards for Pfizer, Regeneron, Replimune, Incyte, natera, and SunPharma. JBAGH participated in consulting/advisory boards from Achilles Tx, AZ, BioNTech, Bristol Myers and Squibb, CureVac, GSK, Immunocore, Instil Bio, Iovance Bio, Merck Serono, Molecular Partners, Merck Sharp & Dohme, Neogene Tx, Novartis, Pfizer, Roche, Serono, Sastra Cell Therapy, Scenic, T-knife, and TRV; has stock options from Neogene Tx, and Sastra Cell Therapy; and receives grant support from Amgen, Asher Bio, BioNTech, Bristol Myers and Squibb, Novartis, and Sastra Cell Therapy. ICGO reports grants from BMS during the conduct of the study; grants, personal fees, and other support from Pfizer, personal fees from Novartis, grants from Merck, and personal fees from Midatech outside the submitted work. JSWB, LEH, LG, WAR, EAA, AD, JST, FA, FD, ES, JC, JDW, LDM have no conflicts of interest to report.

Figures

**Fig. 1**
**Overview of patients in Group 1 and Group 2.** Group 1 consists of patients diagnosed with advanced stage melanoma while pregnant; Group 2 consists of patients who were receiving systemic treatment for an advanced stage melanoma at time of conception. Multiple modes of diagnosis could be used during pregnancy. The total number of patients per stage is displayed first, followed by the sub-staging of the patients within each stage. Staging according to the AJCC 8th categories. Figure only includes systemic treatments. CT, computer tomography; ECOG, Eastern Cooperative Oncology Group; IT, immunotherapy; MRI, Magnetic Resonance Imaging; PET, Positron Emission Tomography (PET); Tx, treatment; w, weeks.

**Fig. 2**
**Overview of imaging modalities during pregnancy and guidance based on distant metastasis risk.** Gy, Gray; MRI, Magnetic Resonance Imaging; PET, Positron Emission Tomography (PET).

See this image and copyright information in PMC

References

1. Arnold M., Singh D., Laversanne M., et al. Global Burden of Cutaneous Melanoma in 2020 and projections to 2040. JAMA Dermatol. 2022;158(5):495–503. doi: 10.1001/jamadermatol.2022.0160. - DOI - PMC - PubMed
1. Lundberg F.E., Stensheim H., Ullenhag G.J., et al. Risk factors for the increasing incidence of pregnancy-associated cancer in Sweden - a population-based study. Acta Obstet Gynecol Scand. 2024;103(4):669–683. doi: 10.1111/aogs.14677. - DOI - PMC - PubMed
1. Michielin O., van Akkooi A., Lorigan P., et al. ESMO consensus conference recommendations on the management of locoregional melanoma: under the auspices of the ESMO guidelines Committee. Ann Oncol. 2020;31(11):1449–1461. doi: 10.1016/j.annonc.2020.07.005. - DOI - PubMed
1. Bannister-Tyrrell M., Roberts C.L., Hasovits C., Nippita T., Ford J.B. Incidence and outcomes of pregnancy-associated melanoma in New South Wales 1994-2008. Aust N Z J Obstet Gynaecol. 2015;55(2):116–122. doi: 10.1111/ajo.12279. - DOI - PubMed
1. Baarslag M.A., Heimovaara J.H., Borgers J.S.W., et al. Severe immune-related enteritis after in utero exposure to pembrolizumab. N Engl J Med. 2023;389(19):1790–1796. doi: 10.1056/NEJMoa2308135. - DOI - PubMed

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Advanced stage melanoma during pregnancy: recommendations from a retrospective, multicentre, registry-based study

Affiliations

Advanced stage melanoma during pregnancy: recommendations from a retrospective, multicentre, registry-based study

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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