Advanced stage melanoma during pregnancy: Real-world management.
Authors: Borgers Jessica S.W. , Johnson Douglas Buckner , Livingstone Elisabeth , Buchbinder Elizabeth Iannotti , Robinson William A , Hamid Omid , Ferreira Michelle , Dimitriou Florentia , Long Georgina V. , Ascierto Paolo Antonio , Daletzakis Antonios , Najjar Yana G. , Hospers Geke , Choi Jacob Seung , Amant Frederic , Tsai Katy K. , Eroglu Zeynep , Haanen John , Glitza Isabella Claudia 
Published: July 2024

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Background: Treatment (tx) of advanced melanoma during pregnancy represents a major challenge. While management of early-stage melanoma is similar to non-pregnant patients (pts), very little data is available on outcome or tx guidelines for pregnant pts with advanced stage. Therefore, we collected real world management data, to ultimately develop management guidelines for these pts. Methods: This retrospective, international, multicenter database, included pts who either were diagnosed with advanced melanoma (newly diagnosed or recurrent) during pregnancy (group 1) or conceived while on systemic tx for melanoma (group 2) between 01/2011–06/2023. Patient, primary tumor and advanced melanoma characteristics, intervention/tx during pregnancy, and outcomes of mother and fetus were collected using a standardized, de-identified form. Results: 68 pts from 7 countries were included, with a total of 72 pregnancies: 60 pregnancies in group 1 and 12 in group 2, including 5 twin pregnancies. Median age at time of pregnancy was 32 (19-42). In group 1, advanced melanoma diagnosis occurred during the 1st trimester in 38%, followed by 3rd (32%), 2nd (22%) and unknown (8%) trimester. 2% had stage II melanoma, 48% stage III, and 50% stage IV. 76% were cutaneous melanoma, 7% mucosal, and 17% other subtypes. BRAF mutations were seen in 70%. Pregnancy was terminated in 15% of cases, and miscarriage occurred in 1 case. Of the 50 live births, 68% were induced and 56% were preterm (38% vaginal, 54% C-section). Median gestational age (MGA) was 34 wks (27-40). Systemic tx was initiated during pregnancy in 8 pts (targeted therapy [TT, 63%], immunotherapy [IT, 37%]). 90% switched or initiated new systemic tx after pregnancy (median time to start of therapy: 28 days; IT 65%, TT 27%, chemo 8%). 5-year overall survival (OS) was 49% (95%CI 34-69), with a median follow-up (MFU) of 26m. In group 2, 82% had cutaneous melanoma and 18% an unknown primary. 91% had a BRAF mutation. 42% of pts received systemic tx for stage III melanoma and 58% for stage IV (IT 75%, TT 25%). 33% of pregnancies were terminated, 8% ended in miscarriage. Of the 8 live births, 43% were preterm, 29% were induced (43% vaginal, 29% C-section). MGA was 35 wks (32-39). Half the pts initiated new or continued tx after pregnancy (IT 50%, TT 50%). 5-year OS was 78% (95%CI 55-100), with MFU of 48m. Of the 57 live births, 1 child born at 26w died after 3 days. No children developed melanoma, despite 5 placentas with melanoma involvement. 4 unexposed children had congenital deficits: prematurity-related (n=3) and congenital hypothyroidism (n=1). 1 child with 3rd trimester Vemurafenib exposure had heart malformations, and 2 experienced toxicity after in uteroIT exposure. Conclusions: This is the largest contemporary dataset of pts diagnosed with advanced melanoma during pregnancy and pts who became pregnant on systemic melanoma therapy, and provides a basis for developing clinical guidelines for this challenging population.