OR27-06 Testicular Function After Immune Checkpoint Inhibitors Treatment

Abstract Disclosure: A. Boutros: None. A. Idan: None. S. Sleiman: None. F. Bacha: None. T. Zhang: None. V. Jayadev: None. A.M. Menzies: None. G.V. Long: AstraZeneca, Bayer, Inc., Boehringer Ingelheim, Bristol-Myers Squibb, Novartis Pharmaceuticals, Pierre Fabre, Regeneron Pharmaceuticals. D.J. Handelsman: None. Introduction: Immune-checkpoint inhibitors (ICIs) have revolutionized cancer treatment, demonstrating durable survival benefits across a wide range of malignancies, from advanced to early-stage disease. While endocrine toxicities of ICIs are well-known, their impact on male reproductive function remains poorly understood. This prospective study aimed to evaluate the effects of ICIs on testicular function in men with melanoma, and no prior gonadotoxic treatments. Study Design: This observational, mixed longitudinal and cross-sectional study enrolled men with melanoma requiring systemic therapy at two centres. Baseline andrological assessments included medical history, physical examination, and sperm cryopreservation. Semen analyses (volume, density, motility, morphology) and reproductive hormone measurements (serum LH, FSH, testosterone, SHBG) were performed at baseline and during follow-up. Patients with prior gonadotoxic treatments such as pelvic radiotherapy were excluded. Changes in reproductive parameters were analysed using mixed-effects models for repeated measures with adjustment for potential confounders. Results: Among 29 young men, aged 25 ± 1 years, with early-stage melanoma (22 stage II/III, 7 stage IV) and minimal prior testis pathology, 26 were included in the prospective analysis after excluding 3 who received gonadotoxic treatments. Treatment regimens included anti-PD1 in 24 patients (9 alone, 7 with anti-CTLA4, 4 with anti-LAG3, and 6 with BREF/MEK inhibitors). Over a median follow-up of 2.8 years (IQR 1.7, 4.5 years), there was a marginally significant reduction in sperm output (34% reduction from baseline median of 193 to 127 million; p=0.053) and sperm density (30% reduction from 61 to 43 million/mL; p=0.075), with no significant changes in sperm motility or morphology, or serum LH, FSH and testosterone. One patient developed persistent azoospermia with increased serum FSH, with normal serum testosterone and LH consistent with autoimmune orchitis. Sensitivity analyses excluding this patient showed no reductions in sperm parameters. Conclusions: ICIs, widely used across multiple cancers, have a mild but clinically relevant impact on spermatogenesis, with no effect on testicular endocrine function. This highlights the importance of sperm cryopreservation prior to ICI initiation and the need for monitoring reproductive function during and after treatment. Further studies are required to elucidate mechanisms and develop protective strategies to preserve male fertility in men undergoing immunotherapy. Presentation: Monday, July 14, 2025