Severe cutaneous and neurologic toxicity in melanoma patients during vemurafenib administration following anti-PD-1 therapy.
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.
Vanderbilt University Medical Center.
Douglas B
DB
Johnson
Vanderbilt University Medical Center.
Erika K
EK
Wallender
Vanderbilt University Medical Center.
Daniel N
DN
Cohen
Vanderbilt University Medical Center.
Sunaina S
SS
Likhari
Vanderbilt University Medical Center.
Jeffrey P
JP
Zwerner
Vanderbilt University Medical Center.
Jennifer G
JG
Powers
Vanderbilt University Medical Center.
Lisa
L
Shinn
Vanderbilt University Medical Center.
Mark C
MC
Kelley
Mayo Clinic Jacksonville.
Richard W
RW
Joseph
Vanderbilt University Medical Center.
Jeffrey A
JA
Sosman
D000328:Adult; D000634:Aminoquinolines / Q000008:administration & dosage / Q000009:adverse effects; D000707:Anaphylaxis / Q000139:chemically induced; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D020275:Guillain-Barre Syndrome / Q000139:chemically induced*; D006801:Humans; D000077271:Imiquimod; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D008545:Melanoma / Q000188:drug therapy*; D008875:Middle Aged; D000077594:Nivolumab; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D012878:Skin Neoplasms / Q000188:drug therapy*; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects; D000077484:Vemurafenib
D000634:Aminoquinolines; D000911:Antibodies, Monoclonal; D007211:Indoles; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D013449:Sulfonamides; D000077484:Vemurafenib; D000077594:Nivolumab; D000077271:Imiquimod
Melanoma; anti-PD-1; immunotherapy; vemurafenib