Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy

• Published in: Cancer immunology research Vol. 1; no. 6; p. 373
• Main Authors: Johnson, Douglas B, Wallender, Erika K, Cohen, Daniel N, Likhari, Sunaina S, Zwerner, Jeffrey P, Powers, Jennifer G, Shinn, Lisa, Kelley, Mark C, Joseph, Richard W, Sosman, Jeffrey A
• Format: Journal Article
• Language: English
• Published: United States 01.12.2013
• Subjects: Adult; Aminoquinolines - administration & dosage; Aminoquinolines - adverse effects; Anaphylaxis - chemically induced; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Drug Eruptions - etiology; Female; Guillain-Barre Syndrome - chemically induced; Humans; Indoles - administration & dosage; Indoles - adverse effects; Melanoma - drug therapy; Middle Aged; Programmed Cell Death 1 Receptor - antagonists & inhibitors; Skin Neoplasms - drug therapy; Sulfonamides - administration & dosage; Sulfonamides - adverse effects; vemurafenib; anti-PD-1; Melanoma; immunotherapy
• ISSN: 2326-6074
• DOI: 10.1158/2326-6066.cir-13-0092

Immune checkpoint inhibitors such as ipilimumab and targeted BRAF inhibitors have dramatically altered the landscape of melanoma therapeutics over the past few years. Agents targeting the programmed cell death-1/ligand (PD-1/PD-L1) axis are now being developed and appear to be highly active clinically with favorable toxicity profiles. We report two patients with BRAF V600E mutant melanoma who were treated with anti-PD-1 agents as first-line therapy without significant toxicity, followed by vemurafenib at disease progression. Both patients developed severe hypersensitivity drug eruptions with multi-organ injury early in their BRAF inhibitor treatment course. One patient subsequently developed acute inflammatory demyelinating polyneuropathy (AIDP) and the other developed anaphylaxis upon low-dose vemurafenib rechallenge. Further investigation of the immune response during combination or sequences of melanoma therapeutics is warranted. Furthermore, clinicians should maintain a high index of suspicion for these toxicities when vemurafenib is administered following an anti-PD-1 agent.