Patients on immunotherapy treatments for lung cancer have experienced repigmentation of their formerly gray hair, according to a new report. Moreover, researchers say, all but one of the patients experiencing this effect also responded well to the therapy, suggesting that hair repigmentation could potentially serve as a marker of treatment response.

In a case series published online July 12 in JAMA Dermatology (2017. doi: 10.1001/jamadermatol.2017.2106 ), Noelia Rivera, MD, of the Universitat Autònoma de Barcelona and her colleagues report findings from 14 patients (13 male, mean age 65) receiving anti–programmed cell death 1 (anti–PD-1) and anti–programmed cell death ligand 1 (anti–PD-L1) therapies to treat squamous cell lung cancer or lung adenocarcinoma, with most (11) receiving nivolumab (Opdivo). All but one patient experienced a diffuse darkening of the hair to resemble its previous color, while the remaining patient’s repigmentation occurred in patches.

Anti–PD-1 and anti–PD-L1 therapies work by preventing tumors from escaping the immune system response and have been seen in other studies associated with skin events including cutaneous eruption, vitiligo, and pruritus. Patients receiving anti–PD-1 therapies for melanoma have been reported to develop vitiligo involving their hair. Hair repigmentation has previously been documented in association with a handful of other drugs used in cancer or rheumatology, including thalidomide, lenalidomide, erlotinib, adalimumab, and etretinate, but the mechanisms by which any of these agents affect hair or skin is poorly understood.

Dr. Rivera and her colleagues wrote in their analysis that gray hair follicles “still preserve a reduced number of differentiated and functioning melanocytes located in the hair bulb. This reduced number of melanocytes may explain the possibility of [repigmentation] under appropriate conditions.” But, there are competing theories as to why this should occur with cancer immunotherapy, they noted. One is that the drugs’ inhibition of proinflammatory cytokines acts as negative regulators of melanogenesis. Another is that melanocytes in hair follicles are activated through inflammatory mediators. Of the patients with hair repigmentation in the study, only one, who was being treated with nivolumab for lung squamous cell carcinoma, had disease progression. This patient was discontinued after four treatment sessions and died. The other 13 patients saw either stable disease or a partial response.

The study received no outside funding, but two investigators disclosed financial relationships with pharmaceutical manufacturers.


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