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Case History

image A 33-year old man presented with a metastatic melanoma that was positive for a somatic mutation in the B-RAF proto-oncogene (BRAF). The primary lesion was a 3.5 mm ulcerated melanoma excised from the left neck with 4/19 lymph nodes positive for melanoma. Despite adjuvant radiotherapy to this area, he had evidence of progressive recurrent disease on positron emission tomography (PET) scan 6 months later, with fluorodeoxyglucose (FDG) avid bilateral cervical lymphadenopathy.

At presentation, he lived with his wife and children. Family planning was not specifically discussed at this point, however there was no suggestion that the patient intended to father more children.

He commenced single agent immunotherapy with the PD-1 (Programmed Cell Death Protein 1) inhibitor pembrolizumab. He tolerated treatment well and had an excellent radiological response to treatment.

During treatment, he separated from his wife and later moved in with a new female partner. Following 18 months of treatment they informed the treating team of their unplanned pregnancy at a gestation of 8 weeks.

The drug manufacturers were contacted for information regarding the safety of pregnancies when conception has taken place whilst the father is being treated with pembrolizumab. The summary of product characteristics (SPC) for pembrolizumab did not have any information on this scenario, and literature search did not reveal any published case reports. Protocols for previous immunotherapy trials have commented that it is not known if pembrolizumab has any adverse effects on the composition of sperm. They recommended that the pregnancy be monitored and any problems with the pregnancy such as spontaneous abortion, miscarriage or fetal abnormalities be reported as serious events.

The patient and his partner decided to continue with the pregnancy, and gave the treating team verbal reports of the progress of the pregnancy. The pregnancy was uneventful and the patient’s partner had a spontaneous vaginal delivery at term. The patient completed 2 years of immunotherapy with complete metabolic response on his PET-CT scan. He has been attending clinic for radiological surveillance accompanied by his partner and child, and there have not been any adverse effects noted in the child’s health and development to date.

What are the possible mechanisms of interaction between immunotherapy and the reproductive system?

Is it safe to conceive during or after treatment with immune checkpoint inhibitors?

What are the recommendations regarding fertility for patients about to receive immune checkpoint inhibitors?

What are the possible mechanisms of interaction between immunotherapy and the reproductive system?

Immune checkpoint inhibitors (CPIs) are increasingly used in the treatment of solid and haematological tumours. Immune CPIs can be used as single agents or in combination with cytotoxic chemotherapy or targeted treatments. CPIs are a form of immunotherapy which also includes other systemic therapies such as Chimeric Antigen Receptor T cell treatment (CAR-T) and oncolytic viral therapies. In this case study we focus on CPIs.

The side effects of CPIs are classically immune-mediated, such ...

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