Potential Association of Impaired Spermatogenesis and Immune Checkpoint Inhibitor Therapy in Patients With Metastatic Melanoma
In a study reported as a research letter in JAMA Oncology, Scovell et al identified a potential association between the use of immune checkpoint inhibitors and impaired spermatogenesis using autopsy tissue findings in men with a history of metastatic melanoma.
The study involved querying of the Johns Hopkins Pathology database and the Johns Hopkins Legacy Gift Rapid Autopsy database for autopsy data on patients with a history of metastatic melanoma who had been treated with ipilimumab, nivolumab, or pembrolizumab for more than 1 month. Patients who had received systemic chemotherapy or radiotherapy to the thorax, abdomen, pelvis, or lower extremities were excluded from analysis.
A control cohort was matched for age at tissue acquisition. Control autopsy samples came from men with a history of metastatic melanoma who had never received immune checkpoint inhibitors, chemotherapy, or radiotherapy to the thorax, abdomen, pelvis, or lower extremities.
Querying of more than 10,000 potential participants identified a total of 13 men (median age = 54 years) with metastatic melanoma who had testicular autopsy tissue specimens available. Of the 13 men, 7 had received immune checkpoint inhibitors and 6 had not. There were no differences between the two groups in age at diagnosis, age at death, or time to autopsy.
Impaired spermatogenesis was identified in six (86%) of seven men who had received immune checkpoint inhibitors, including focal active spermatogenesis in one, hypospermatogenesis in two, and Sertoli-cell–only syndrome in three. In comparison, impaired spermatogenesis was identified in two (33%) of six men who had not received immune checkpoint inhibitors.
"Identifying the association of immune checkpoint inhibitors with future fertility will be an important step in determining whether male fertility preservation is an essential component to pretreatment counseling."— Scovell et al
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No increased peritubular hyalinization or fibrosis was observed in any patients who received immune checkpoint inhibitors, and no Leydig cell abnormalities were observed in any patients.
The investigators concluded, “Fertility preservation is an important facet in the care of men with cancer who are within their reproductive years…. One key to improving cancer survivorship and quality of life is to anticipate potential treatment-associated sequelae. Identifying the association of immune checkpoint inhibitors with future fertility will be an important step in determining whether male fertility preservation is an essential component to pretreatment counseling. A limitation of our study was the small sample size. To our knowledge, the data herein are the first to evaluate the association of immune checkpoint inhibitors with testicular function, but prospective evaluations will be essential to determining the gonadotoxic effect of immune checkpoint inhibitors.”
Amin S. Herati, MD, of the James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, is the corresponding author for the JAMA Oncology article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.