Establishing the association of immunotherapy with spermatogenesis is an essential step for the preservation of male fertility
A research letter published in JAMA Oncology recently discussed the potential association between immune checkpoint inhibitors (ICI) and damage to spermatogenesis, after autopsy tissue findings in men with a history of metastatic melanoma.
The study relied on the Johns Hopkins Pathology and Johns Hopkins Legacy Gift Rapid Autopsy database to obtain autopsy data from patients with a history of metastatic melanoma treated with ipilimumab, nivolumab or pembrolizumab for more than a month. Patients who received chemotherapy or systemic radiation therapy in the chest, abdomen, pelvis or lower limbs were excluded from the analysis.
A control cohort was paired by age in tissue acquisition. The control autopsy samples belonged to men with a history of metastatic melanoma who never received ICI, chemotherapy or radiation therapy in the chest, abdomen, pelvis or lower extremities.
The consultation of more than 10,000 participants identified 13 men (mean age 54 years) with metastatic melanoma who had testicular tissue autopsy samples available. Of these 13 individuals, 7 received ICI and 6 did not. There were no differences between the two groups in diagnostic age, age of death or autopsy time.
Damage to spermatogenesis was identified in 6 (86%) of the 7 men who received ICI, including active focal spermatogenesis in one patient, hypo-spermatogenesis in two and Sertoli single cell syndrome in three of them. Of the 6 men who did not receive ICI, impaired spermatogenesis was identified in two (33%). Peritubular hyalinization and increased fibrosis were not identified in any patient who received ICI, as well as no abnormality of Leydig cells.
A limitation of the trial is the small sample size. However, identifying the association of ICI with spermatogenesis is an essential step for pre-treatment discussion and advice between doctor and patient on the preservation of male fertility. Prospective assessments are necessary to confirm the gonadotoxic effect of ICI.
Scovell JM, Benz K, Samarska I, et al. Association of Impaired Spermatogenesis With the Use of Immune Checkpoint Inhibitors in Patients With Metastatic Melanoma. JAMA Oncol. Published online June 18, 2020. doi:10.1001/jamaoncol.2020.1641