Sunday, September 4, 2016

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


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


  1. Came to bring words of confort for those with vitiligo and melanoma.

    I had a mole removed 8 years ago in a public hospital here in Brazil and never went pick the resultus.

    4 years later i developed vitiligo on my face and chest. tought it was becouse of stress..

    last year I had an injury at the gym and my lymph nodes had swollen to the size of a tenis ball. I that time thought it was becouse of the injuty, it was painless, and I spent 4 more months without going to the doctor...and still working out everyday. Doing high intensity exercises...

    When I went to the doctor we dicovered about the mole, that I lived 7 years with melanoma and that the vitiligo was becouse of it.

    I had 31 lymphnodes ressected, which 13 was melanoma postive. Did radiotherapy for 30 days.

    When I began treatment Ipilimumab was not "brazilian fda" approved. So I am curretly on my 15th month of High dose PegInterferon...

    So far I dont have no signs of Melanoma in my body. Amazing, I think. By what happened I shoud be stage IV. Not IIIc.

    I hate a relation o gratitude and hate about vitiligo.

    I started depigment on pourpse what is left of melanin on my face whin Monobenzone at 20%...There are some studies that tries to mimic the effect of vitiligo using Monbenzone against melanin in general and melanoma cells...In vitro.

    My depigmentation with Monobenzone is purely for cosmetic reason today. To have an even tone in my face ( about 90% of my face has no pigment due to vitiligo)...Dont want to get better from vitiligo, really. So why not expend it a little bit.

    For the doctors reading this I am using Monobenzone during my HD Interferon treatment. My doctor is not aware of my Monobenzone usage. Side effects have worsen, but is tolerable.

    Thats it. Luck to you guys.

    Rodrigo Faria

  2. Sorry that you are dealing with this. It shows the importance of dealing with melanoma sooner rather than later, though you may have had no other treatment options at the time of your original dx other than 'watch and wait'. From what you describe you would indeed be Stage III. I am glad the resection and radiation have eradicated the positive nodes. I hope you have had scans to determine the status of the rest of your body. Unfortunately, interferon has been proven to have little significant impact on melanoma and NO effect on overall survival. Hence forth I hope you remain vigilent and can attain a better systemic therapy should you need it. I wish you well.

    1. Hi Les, how are you?

      Yes, I know, there is no impact on overal survival, the treatment with Intrerferon.

      All these medicines including Ipilimumab was not allowed to be used in the adjuvant setting. Stage III patients could only be offered Interferon, unfortunally.

      My luck is that vitiligo with any therapy I think has a promisse of a better outcome. Including the treatment with Interferon. There is a pretty famous study that I can share with you:

      Prognostic Significance of Autoimmunity during Treatment of Melanoma with Interferon:

      Now I have Nivolumab available for me, but my insurance plan wont pay it yet bacause I am not a metastatic patient.

      I have scans done every 3 months. No signs of the disease.

      Got to know your blog searching for new researches on melanoma and. vitiligo.

      Les, good luck tou you and thanks for putting up good information on your blog.

      Abraços do Brasil.

    2. I understand. Adjuvant treatments are sorely lacking in most countries, including here in the United States, and drives me crazy! You can only do the best you can and it sounds as though you are. Additionally, as noted in the links to many articles noted above...yes...vitiligo is generally a good prognostic sign. Bon suerte, mi amigo. C