Friday, April 20, 2018

Creating vitiligo with monobenzone to help melanoma patients????


We have known for some time that melanoma patients who develop vitiligo do better than those who do not.  Lot's of posts regarding vitiligo and melanoma can be seen here:  All things vitiligo

I've thought for a long time, that if we could figure out the exact cause of the development of vitiligo in some...and trigger it in others...it would certainly be a good thing!  Now, there's this ~

Anti-Melanoma immunity and local regression of cutaneous metastases in melanoma patients treated with monobenzone and imiquimod; a phase 2 a trial. Teulings, Tjin, Willemsen, et al. Oncoimmunology. 2018 Jan 15.
Vitiligo development in melanoma patients during immunotherapy is a favorable prognostic sign and indicates breakage of tolerance against melanocytic/melanoma antigens. We investigated a novel immunotherapeutic approach of the skin-depigmenting compound monobenzone synergizing with imiquimod in inducing antimelanoma immunity and melanoma regression. Stage III-IV melanoma patients with non-resectable cutaneous melanoma metastases were treated with monobenzone and imiquimod (MI) therapy applied locally to cutaneous metastases and adjacent skin during 12 weeks, or longer. Twenty-one of 25 enrolled patients were evaluable for clinical assessment at 12 weeks. MI therapy was well-tolerated. Partial regression of cutaneous metastases was observed in 8 patients and stable disease in 1 patient, reaching the statistical endpoint of treatment efficacy. Continued treatment induced clinical response in 11 patients, including complete responses in three patients. Seven patients developed vitiligo-like depigmentation on areas of skin that were not treated with MI therapy, indicating a systemic effect of MI therapy. Melanoma-specific antibody responses were induced in 7 of 17 patients tested and melanoma-specific CD8+T-cell responses in 11 of 15 patients tested. These systemic immune responses were significantly increased during therapy as compared to baseline in responding patients. This study shows that MI therapy induces local and systemic anti-melanoma immunity and local regression of cutaneous metastases in 38% of patients, or 52% during prolonged therapy. This study provides proof-of-concept of MI therapy, a low-cost, broadly applicable and well-tolerated treatment for cutaneous melanoma metastases, attractive for further clinical investigation.

Okay,  So, in this trial 25 Stage III/IV folks (though only 21 were evaluated in the end) had monobenzone and imiquimod applied to their skin on and around existing melanoma skin lesions.  At 12 weeks Partial Regression was noted in 8 patients and 1 had stable disease.  As treatment continued, a Clinical Response was noted in 11 patients and 3 had a Complete Response.  Vitiligo (depigmentation of the skin) was noted in areas NOT treated in 7 patients, implying a systemic response to this therapy.

What is not clear to me is whether or not these patients had been treated with any other therapy...like prior or concomitant immunotherapy.  I mean, if I were a Stage IV patient (Wait, I am!!!  HA!) I don't know that I would settle for just applying a cream.  On the other hand, if they would treat me systemically AND apply a cream....I would totally go for it!  It may be that these peeps had actual cutaneous lesions, almost like intrasit mets or something, given the way the authors describe the application process.  This condition is not something all Stage III/IV melanoma patients have.  Unfortunately, information about the exact sort of lesion and the prior or simultaneous systemic treatment of the patients included here is not divulged in this abstract.  Even so, monobenzone applied to the skin with imiquimod sounds like a low risk procedure with some positive results.  

Here's to a whiter shade of pale!!! Keep on teaching us, ratties! - c

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