Hypersensitivity skin reactions in melanoma patients treated with vemurafenib after ipilimumab therapy.

Abstract

8515 Background: Ipilimumab (IPI) and vemurafenib (VEM) each improve overall survival for patients (pts) with metastatic melanoma. Both are FDA-approved and are being used in pts with BRAFV600E-mutated metastatic melanoma. We previously described cases of prominent skin eruptions associated with VEM in pts who had previously received IPI. Methods: We have updated our experience of BRAFV600E-mutated melanoma pts treated with VEM who had previously received IPI. Pts were treated at our center from January 2007 to January 2012. Data were collected under an approved IRB waiver. Results: Sixteen melanoma pts were treated with VEM after having received IPI. The most common drug-related adverse event (AE) associated with VEM was rash, occurring in 13/16 patients (81.3%, 95% CI 56.5-93.2). Four pts developed a severe, Grade 3, maculopapular rash within 8 days of starting VEM. Biopsies in 2 pts revealed spongiotic and perivascular dermatitis with eosinophils consistent with a drug hypersensitivity reaction. Hypersensitivity reactions did not progress to life-threatening reactions such as anaphylaxis or Stevens-Johnson syndrome, nor did they result in VEM dose discontinuation. Reactions were managed with corticosteroids and dose modifications. Grade 3 rash strongly correlated with initiating VEM within one month of IPI (Fisher’s exact test, p = 0.007) and was not associated with the dose of prior IPI, the number of prior doses, or immune-related AEs. The incidence of Grade 3 rash in this pt cohort was significantly higher than in pts treated on the phase III trial of VEM (4/16, 25% versus 28/336, 8%; χ2 = 5.13, Df = 1, p = 0.02). The objective overall response for VEM was 50% (95% CI 26.5-73.4), which is similar to response rates seen on the phase II and III trials. Conclusions: In pts receiving VEM who have previously received IPI, dermatologic AEs appear to be more common. This effect seemed most pronounced if VEM was given within one month of completing IPI. Although more data are necessary to confirm this apparent association, we speculate that the release of immune checkpoint inhibition by IPI may predispose pts to hypersensitivity skin reactions to VEM.