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

Douglas B Johnson; Erika K Wallender; Daniel N Cohen; Sunaina S Likhari; Jeffrey P Zwerner; Jennifer G Powers; Lisa Shinn; Mark C Kelley; Richard W Joseph; Jeffrey A Sosman

doi:10.1158/2326-6066.CIR-13-0092

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

Journal article

Open access

Peer reviewed

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

Douglas B Johnson, Erika K Wallender, Daniel N Cohen, Sunaina S Likhari, Jeffrey P Zwerner, Jennifer G Powers, Lisa Shinn, Mark C Kelley, Richard W Joseph and Jeffrey A Sosman

Cancer immunology research, Vol.1(6), pp.373-377

12/2013

DOI: 10.1158/2326-6066.CIR-13-0092

PMCID: PMC3905602

PMID: 24490176

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https://doi.org/10.1158/2326-6066.CIR-13-0092View

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Abstract

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.

Drug Eruptions - etiology

Guillain-Barre Syndrome - chemically induced

Skin Neoplasms - drug therapy

Humans

Middle Aged

Aminoquinolines - administration & dosage

Antibodies, Monoclonal - adverse effects

Antineoplastic Combined Chemotherapy Protocols - adverse effects

Programmed Cell Death 1 Receptor - antagonists & inhibitors

Indoles - administration & dosage

Indoles - adverse effects

Anaphylaxis - chemically induced

Antibodies, Monoclonal - administration & dosage

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Melanoma - drug therapy

Sulfonamides - adverse effects

Adult

Female

Sulfonamides - administration & dosage

Aminoquinolines - adverse effects

Details

Title: Subtitle: Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy
Creators: Douglas B Johnson - Vanderbilt University Medical Center
Erika K Wallender - Vanderbilt University Medical Center
Daniel N Cohen - Vanderbilt University Medical Center
Sunaina S Likhari - Vanderbilt University Medical Center
Jeffrey P Zwerner - Vanderbilt University Medical Center
Jennifer G Powers - Vanderbilt University Medical Center
Lisa Shinn - Vanderbilt University Medical Center
Mark C Kelley - Vanderbilt University Medical Center
Richard W Joseph - Mayo Clinic Jacksonville
Jeffrey A Sosman - Vanderbilt University Medical Center
Resource Type: Journal article
Publication Details: Cancer immunology research, Vol.1(6), pp.373-377
Publisher: United States
DOI: 10.1158/2326-6066.CIR-13-0092
PMID: 24490176
PMCID: PMC3905602
ISSN: 2326-6066
eISSN: 2326-6074
Grant note: K12 CA 0906525 / NCI NIH HHS K12 CA090625 / NCI NIH HHS
Language: English
Date published: 12/2013
Academic Unit: Dermatology
Record Identifier: 9984025471102771

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