Skin reactions in a subset of patients with stage IV melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 monoclonal antibody as a single agent.
OBJECTIVE
To describe the clinical and histologic manifestations of skin reactions incidentally noted in patients with stage IV melanoma who were treated with up to 9 mg/kg of a humanized monoclonal antibody reactive against human cytotoxic T-lymphocyte antigen 4 (anti-CTLA-4) as a single agent every 3 weeks.


METHODS
Single-institution prospective study.


METHODS
Patients treated with anti-CTLA-4 as a sole agent were prospectively referred for clinicopathologic characterization of skin reactions occurring during treatment.


METHODS
Specific clinicopathologic features were determined by means of a detailed history, a physical examination, conventional histologic analysis, antibody staining, and complete blood cell counts.


RESULTS
Nine (14%) of 63 consecutive patients treated with anti-CTLA-4 as a sole agent developed skin eruptions that were attributed to anti-CTLA-4 in 8 of them. Skin lesions consisted primarily of discrete, pruritic, erythematous, minimally scaly papules that typically coalesced into thin plaques on the trunk and extensor surfaces of the extremities. Extensive alopecia was also noted in 1 patient. Histologically, a superficial, perivascular CD4+-predominant T-cell infiltrate with eosinophils in the dermis, rare dyskeratotic cells, and mild epidermal spongiosis were present. An increase (compared with pretreatment values) in the peripheral blood eosinophil frequency was observed in patients at the time of skin eruptions (P = .006).


CONCLUSIONS
Specific features of the skin eruption dermatitis with increased tissue and peripheral blood eosinophil levels in a subset of treated patients. Specific features of skin eruption associated with anti-CTLA-4 resemble those described for maculopapular reactions to medications.
Jaber
Samer H
SH
Dermatology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1908, USA.
Cowen
Edward W
EW
Haworth
Leah R
LR
Booher
Susan L
SL
Berman
David M
DM
Rosenberg
Steven A
SA
Hwang
Sam T
ST
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology*; D001706:Biopsy; D060908:CTLA-4 Antigen; D003875:Drug Eruptions / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009367:Neoplasm Staging; D011446:Prospective Studies; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human