All things vitiligo

I developed the beginnings of vitiligo early (54 days after my first dose) in my nivo/Opdivo trial.  By dose 8 (102 days in) it was very apparent and increasing.  Here are some previous posts (starting with those most recently posted and going back to 2011!!):

Vitiligo: Again associated with response with anti-PD1 in melanoma patients

Itching and vitiligo associated with progression free survival after Pembro/Keytruda???!

ASCO 2015: Adverse effects from Nivo and how they are associated with survival

Vitiligo....a good prognostic indicator for melanoma!

Strength and beauty = Chantelle Brown-Young....and me???

Beauty...John Legend...Nobody in the World...he got it right!

Vitiligo and melanoma

Vitiligo...set # 2...Looking for Melanoma Answers!!

Vaccines, melanoma and vitiligo

Vitiligo

A whiter shade of pale

Now there are these:

Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis.  Teulings, Limpens, Jansen, et al.  J Clin Oncol. 2015 Mar.

Vitiligo-like depigmentation in patients with melanoma may be associated with more favorable clinical outcome. We conducted a systematic review of patients with stage III to IV melanoma treated with immunotherapy to determine the cumulative incidence of vitiligo-like depigmentation and the prognostic value of vitiligo development on survival.  We systemically searched and selected all studies on melanoma immunotherapy that reported on autoimmune toxicity and/or vitiligo between 1995 and 2013. Methodologic quality of each study was appraised using adapted criteria for systematic reviews in prognostic studies. Random-effect models were used to calculate summary estimates of the cumulative incidence of vitiligo-like depigmentation across studies. The prognostic value of vitiligo-like depigmentation on survival outcome was assessed using random-effects Cox regression survival analyses.  One hundred thirty-seven studies were identified comprising 139 treatment arms (11 general immune stimulation, 84 vaccine, 28 antibody-based, and 16 adoptive transfer) including a total of 5,737 patients. The overall cumulative incidence of vitiligo was 3.4%. In 27 studies reporting individual patient data, vitiligo development was significantly associated with both progression-free-survival and overall survival, indicating that these patients have two to four times less risk of disease progression and death, respectively, compared with patients without vitiligo development.  Although vitiligo occurs only in a low percentage of patients with melanoma treated with immunotherapy, our findings suggest clear survival benefit in these patients. Awareness of vitiligo induction in patients with melanoma is important as an indicator of robust antimelanoma immunity and associated improved survival.

Association of Vitiligo With Tumor Response in Patients With Metastatic Melanoma Treated With Pembrolizumab.  Hua, Boussemart, Mateus, et al.  JAMA Dermatol. 2016 Jan.

Vitiligo is an autoimmune skin disorder that reacts against melanocytes. The association of vitiligo with tumor response in patients with melanoma who undergo immunotherapy has been reported but is still controversial.  To prospectively evaluate the appearance of vitiligo in patients receiving pembrolizumab, a monoclonal antibody directed against the programmed death cell receptor.

This prospective observational study was conducted from January 1, 2012, through September 24, 2013, in a single tertiary care hospital with a unit dedicated to patients with melanoma. Sixty-seven patients with metastatic melanoma who received pembrolizumab treatment in the context of a phase 1 study were included and screened for the emergence of vitiligo. Data were collected from January 1, 2012, to February 28, 2014, and analyzed from February through December 2014.  Objective tumor response with regard to the occurrence of vitiligo in patients receiving pembrolizumab therapy. Correlation between vitiligo occurrence and overall survival was also estimated using the Kaplan-Meier product-limit method and compared with a log-rank test. To prevent guarantee- or lead-time bias, a landmark analysis approach after 12, 16, and 20 weeks of treatment was retained.

Of the 67 patients included in the study, 17 (25%) developed vitiligo during pembrolizumab treatment and 50 (75%) did not. An objective (complete or partial) response to treatment was associated with a higher occurrence of vitiligo (12 of 17 [71%] vs 14 of 50 [28%];). The time to onset of vitiligo ranged from 52 to 453 (median, 126) days from the start of treatment. Of the 17 patients with vitiligo, 3 (18%) had a complete response, 9 (53%) had a partial response, 3 (18%) had stable disease, and 2 (12%) had progressive disease at the final follow-up. All the patients treated with pembrolizumab who developed vitiligo were alive at the time of analysis, with a median follow-up of 441 days. Vitiligo, a clinically visible immune-related adverse event could be associated with clinical benefit in the context of pembrolizumab treatment.

Correlation between vitiligo occurrence and clinical benefit in advanced melanoma patients treated with nivolumab: A multi-institutional retrospective study.  Nakamura, Tanaka, Asami, et al.  J Dermatol. 2016 Aug 11. 

Vitiligo is occasionally seen in melanoma patients. Although several studies indicate a correlation between vitiligo occurrence and clinical response in melanoma patients receiving immunotherapy, most studies have included heterogeneous patient and treatment settings. The aim of this study is to investigate the correlation between the occurrence of vitiligo and clinical benefit of nivolumab treatment in advanced melanoma patients. We retrospectively reviewed unresectable stage III or IV melanoma patients treated with nivolumab. Of 35 melanoma patients treated with nivolumab, 25.7% (9/35) developed vitiligo during treatment. The time from the start of nivolumab treatment to occurrence of vitiligo ranged 2-9 months (mean, 5.2). Of nine patients who developed vitiligo, two (22.2%) had a complete response to nivolumab and two (22.2%) had a partial response. The objective response rate was significantly higher in patients with vitiligo than in patients without vitiligo (4/9 [44.4%] vs 2/26 [7.7%]). The mean time to vitiligo occurrence in patients achieving an objective response was significantly less than that in patients who showed no response (3.1 vs 6.8 months). Vitiligo occurrence was significantly associated with prolonged progression-free and overall survival. At the 20-week landmark analysis, however, vitiligo was not associated with a statistically significant overall survival benefit. The occurrence of vitiligo during nivolumab treatment may be correlated with favorable clinical outcome.

Wishing you a whiter shade of pale!!! And in case you were wondering, Chantelle Brown-Young (aka Winnie Harlow) is STILL strong and beautiful (see the 5th link above).  Here she is hanging with Bey at the VMA's!!! 

Here's to living large - no matter our skin! - c