Hair depigmentation as an indicator of durable response to CTLA-4 therapy.

Abstract

8571 Background: Treatment with CTLA-4 monoclonal antibodies for metastatic melanoma has been known to induce immunologically related adverse events. It is unclear if these events correlate with clinical responses. We report here, for the first time, the occurrence of hair depigmentation following therapy with CTLA-4 monoclonal antibodies that correlate with durable clinical responses. No non-responders developed any hair depigmentation. Methods: Patients (pts) enrolled onto 2 clinical trials at NYU using either ipilimumab (ipi) or tremelimumab (treme) for metastatic melanoma were evaluated. 43 pts were accrued (33-ipi and 10-treme). 11 pts achieved long-term, durable responses (3 complete responses and 8 partial responses) lasting over a median of 24 months. 5F:6M Age range: 37-78. All had normal baseline LDH levels. Results: Six pts developed sudden hair depigmentation starting with the eyebrows. Median time to depigmentation was 10 months. All 6 pts have continued to have either complete depigmentation of all body hair or the development of diffuse vitiligo. All of these pts have remained with stable disease or complete resolution of disease ranging from 24-36 months. Five of 6 had normal baseline total lymphocyte counts. One with low baseline lymphocyte counts normalized following therapy. All pts had prior therapies including biologics, immunotherapy and/or chemotherapy. All 6 pts also developed other immunologic-related toxicities including rash (6), pruritis (4), diarrhea (4), grade III hypophysitis (2). The remaining 5 pts without hair depigmentation remain with stable disease ranging from 24-48 months. Immune related toxicities in these include rash (4), pruritis (3), diarrhea (2) and myalgias (1). Tumor tissue from all 11 responders are being analyzed for tumor infiltration with CD3 T cells, infiltrating TILs, microRNA and SNPs. Blood samples drawn before and after response to therapy will be evaluated for anti-NY-ESO-1 antibodies. Conclusions: To our knowledge, this is the first report of immune related hair depigmentation in metastatic melanoma patients treated with CTLA-4 monoclonal antibodies who achieve durable responses. Scientific correlates being performed on blood and tissues and will be presented. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Pfizer