Association of Impaired Spermatogenesis With the Use of Immune Checkpoint Inhibitors in Patients With Metastatic Melanoma

Scovell, Jason M.; Benz, Karl; Samarska, Iryna; Kohn, Taylor P.; Hooper, Jody E.; Matoso, Andrés; Herati, Amin S.

doi:10.1001/jamaoncol.2020.1641

Cited by 34 publications

(24 citation statements)

References 7 publications

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“…In a recent case series, Scovell et al. 24 retrospectively analyzed testicular histology of patients treated with anti-PD1 and anti-CTLA4 that underwent autopsy. An age-matched control cohort not treated with immunotherapy was used.…”

Section: Primary Hypogonadismmentioning

confidence: 99%

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

2021

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Immune checkpoint inhibitors (i.e. anti-PD1, anti-PDL1, and anti-CTLA4) have revolutionized the therapeutic approach of several cancer types. In a subset of metastatic patients, the duration of the response is so long that a cure might be hypothesized, and a treatment discontinuation strategy could be proposed. Considering that long-term efficacy, some patients could also plan to have a child. Moreover, immunotherapy is moving to the early setting in several diseases including melanoma and breast cancer that are common cancers in young patients. However, there is a paucity of data about their potential detrimental effect on fertility, pregnancy, or sexuality. Herein, we conducted a systematic review with the aim to comprehensively collect the available evidence about fertility, pregnancy, and sexual adverse effects of checkpoint inhibitors in order to help clinicians in daily practice and trialists to develop future studies.

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Section: Primary Hypogonadismmentioning

confidence: 99%

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

2021

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“…Recently, Scovell et al . reported that spermatogenesis disorders were observed in six out of seven autopsy testicular specimens from patients who received ICIs as a treatment for metastatic malignant melanoma 6 . As seminiferous tubules are immunologically isolated by the blood–testis barrier, PD‐1 and CTLA are mechanically inhibited and have less effect; however, further investigations with an increased number of cases with longer follow up should be carried out to confirm these preliminary results with a multicenter collaborative study.…”

Section: Control (N = 20) Chemotherapeutic Agents (N = 31) Tki/ici (N = 25) P‐valuementioning

confidence: 89%

Effect of tyrosine kinase inhibitors and immune checkpoint inhibitors on spermatogenesis in humans

et al. 2021

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“…However, clinical reports on the impact of melanoma therapy on spermatogenesis are rare. 46 , 47 , 48 To date, there are two reports published on acute orchitis under ICI therapy with either pembrolizumab 49 or nivolumab plus ipilimumab. 50 Further evidence comes from a retrospective cadaver study.…”

Section: Recommendationsmentioning

confidence: 99%

“… 50 Further evidence comes from a retrospective cadaver study. 48 Herein, the pathology and autopsy database from Johns Hopkins University was searched for testicular biopsies from patients who had been treated with ICI. In only one out of seven patients, a normal spermatogenesis was found histologically.…”

Section: Recommendationsmentioning

confidence: 99%

Fertility preservation and management of pregnancy in melanoma patients requiring systemic therapy

et al. 2021

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Melanoma is one of the most common cancers in adolescents and adults at fertile age, especially in women. With novel and more effective systemic therapies that began to profoundly change the dismal outcome of melanoma by prolonging overall survival, the wish for fertility preservation or even parenthood has to be considered for a growing portion of melanoma patients—from the patients' as well as from the physicians' perspective. The dual blockade of the mitogen-activated protein kinase pathway by B-Raf proto-oncogene serine/threonine kinase and mitogen-activated protein kinase inhibitors and the immune checkpoint inhibition by anti-programmed cell death protein 1 and anti-cytotoxic T-lymphocyte-associated protein-4 monoclonal antibodies constitute the current standard systemic approaches to combat locally advanced or metastatic melanoma. Here, the preclinical data and clinical evidence of these systemic therapies are reviewed in terms of their potential gonadotoxicity, teratogenicity, embryotoxicity and fetotoxicity. Recommendations for routine fertility and contraception counseling of melanoma patients at fertile age are provided in line with interdisciplinary recommendations for the diagnostic work-up of these patients and for fertility-protective measures. Differentiated recommendations for the systemic therapy in both the adjuvant and the advanced, metastatic treatment situation are given. In addition, the challenges of pregnancy during systemic melanoma therapy are discussed.

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Association of Impaired Spermatogenesis With the Use of Immune Checkpoint Inhibitors in Patients With Metastatic Melanoma

Cited by 34 publications

References 7 publications

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

Checkpoint inhibitors, fertility, pregnancy, and sexual life: a systematic review

Effect of tyrosine kinase inhibitors and immune checkpoint inhibitors on spermatogenesis in humans

Fertility preservation and management of pregnancy in melanoma patients requiring systemic therapy

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