AT AAD 2015

SAN FRANCISCO (FRONTLINE MEDICAL NEWS) – Pregnancy increases the risk of poor outcomes in melanoma, according to a review of melanoma cases at the Cleveland Clinic.

The effect of pregnancy on melanoma has been debated for more than a decade. Some studies have found evidence of worse outcomes, but others have not. That prompted Dr. Natasha Mesinkovska, a dermatologist at the clinic, and her colleagues to review their own melanoma outcomes over the past 20 years. They compared 49 women who were pregnant or within a year of pregnancy at diagnosis, with 418 women of childbearing age who were not pregnant. All the patients had at least 2 years follow-up.

Mortality (20% vs. 10.3%; P = .06); recurrence (12.5% vs. 1.4%; P < .001); metastasis (25% vs. 12.7%; P = .03); and the use of radiation and chemotherapy were all more common in the pregnancy group. On logistic regression, women who were pregnant or recently pregnant at the time of melanoma diagnosis were 5.1 times more likely to die of the disease than those who weren’t (P = .03), Dr. Mesinkovska reported at the annual meeting of the American Academy of Dermatology.

The findings prompted the investigators to compare histologic specimens from 17 pregnant and 14 nonpregnant women to find an explanation.

Pregnancy melanomas had reduced PD-1 [programmed cell death] expression (18.3 vs. 45 cells per high-power field [hpf]); decreased CD-3 [cluster of differentiation 3] (191.7 vs. 265.7 cells/hpf); and increased CD-3/PD-1 ratios (57.4 vs. 8.3).

The findings were statistically significant and may have treatment implications for the use in recently pregnant women of antibodies against PD-1 cell-surface receptors, a class of biologics that include nivolumab and pembrolizumab, both approved in 2014 for advanced melanoma. With reduced expression of PD-1, tumors arising around pregnancy might not be as sensitive to such agents.

Labeling for both biologics, however, note the risk of fetal harm, and advise the use of effective contraception while on the agents and for several months after their discontinuation. Both agents should also be discontinued during breastfeeding.

“Immune ignorance may predominate in melanoma specimens in pregnancy. Most novel melanoma therapies target immune modulation. There’s a need in some pregnant women for neoadjuvant treatment prior to immunotherapy to convert them to an inflamed phenotype,” Dr. Mesinkovska said.

Dr. Mesinkovska said she has no relevant financial disclosures.


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