Abstract
Immune checkpoint inhibition has resulted in significant efficacy across many cancer types, including melanoma. Melanoma is the second most common cancer among those of reproductive age, yet the reproductive toxicities of adjuvant and first-line immunotherapy are largely unknown.The normal innate and adaptive immune systems play a vital role in reproductive organ homeostasis of men and women and are essential for implantation, fertility, and a successful pregnancy. The programmed cell death-1 receptor/programmed cell death receptor ligand-1 (PD-1/PD-L1) pathway is essential in several aspects of fertility and pregnancy. Recent studies have largely focused on the role of the PD-1/PD-L1 pathway in fetomaternal tolerance, highlighting the importance of intact immune regulation in promoting a successful pregnancy.In this review, we describe a case of a reproductive-aged female with stage IIIC melanoma who sought guidance on family planning after pembrolizumab therapy. We discuss the known fertility-related toxicities of immune checkpoint inhibitors, the potential targets for reproductive toxicity in males and nonpregnant females, and the implications of anti–PD-1 therapy in relation to fetomaternal tolerance. Informed decision making will benefit from data and consensus.
© 2022 by American Society of Clinical OncologySUPPORT
Supported by the National Cancer Institute of the National Institutes of Health under Award Number K12CA076917 (C.J.H.).
Conception and design: Anne E. Kim, Kyle Stimpert, Rebecca L. Flyckt, Sophia C. Weinmann, Christopher J. Hoimes
Collection and assembly of data: Anne E. Kim, Christopher J. Hoimes
Data analysis and interpretation: Anne E. Kim, Ariel Nelson, Rebecca L. Flyckt, Nannan Thirumavalavan, Karen C. Baker, Christopher J. Hoimes
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
Minding the Bathwater: Fertility and Reproductive Toxicity in the Age of Immuno-Oncology
The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/op/authors/author-center.
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Nannan Thirumavalavan
Consulting or Advisory Role: Endo Pharmaceuticals
Karen C. Baker
Consulting or Advisory Role: Frame Fertility
Sophia C. Weinmann
Stock and Other Ownership Interests: SI Bone, Humacyte
Christopher J. Hoimes
Honoraria: Seattle Genetics
Consulting or Advisory Role: Bristol Myers Squibb, Eisai, Prometheus, Seattle Genetics, Genentech/Roche, Merck Sharp & Dohme, 2bPrecise
Speakers' Bureau: Bristol Myers Squibb, Genentech/Roche, Astellas Pharma, Seattle Genetics, Eisai
Research Funding: Merck Sharp & Dohme (Inst), Janssen Oncology (Inst), Novartis (Inst), Alkermes (Inst), Dynavax Technologies (Inst), Nektar (Inst), NanoCarrier (Inst), Seattle Genetics (Inst), Astellas Pharma (Inst), Bristol Myers Squibb Foundation (Inst), BioNTech SE (Inst), Crispr Therapeutics (Inst), NeoImmuneTech (Inst), Mirati Therapeutics (Inst), BioNTech SE (Inst)
Uncompensated Relationships: 2bPrecise (Inst)
No other potential conflicts of interest were reported.
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