title: Drug-induced cutaneous vasculitis in patients with non-Hodgkin lymphoma treated with the novel proteasome inhibitor bortezomib: a possible surrogate marker of response?
abstract: Bortezomib is the first proteasome inhibitor to be approved for use in haematological malignancies. Although a rash has been described as a common adverse event associated with the drug, it has not been well characterised. Based on three phase II studies of bortezomib in patients with non-Hodgkin lymphoma (140 assessable patients), we identified 26 patients who developed a unique erythematous maculopapular rash during treatment, six of whom underwent cutaneous biopsy. Punch biopsy in six patients revealed a perivascular lymphocytic infiltrate without evidence of lymphoma, consistent with a non-necrotising cutaneous vasculitis. The combined overall response rate was 41%. The response in the 26 patients who developed a rash was 73%, compared with 33% in patients who did not. The odds ratio for response given the development of a rash was 4.6 (95% CI, 1.7-12.4, P = 0.001). This is the first report to characterise a vasculitic rash associated with bortezomib, and to show a relationship between development of the rash and response to treatment. Unlike classic hypersensitivity type reactions, this vasculitic rash may not necessarily prompt cessation of drug. In fact, the development of an isolated cutaneous vasculitis may portend a better clinical response to bortezomib in some patients.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gerecitano
authors.forename: Andre
authors.initials: A
authors.lastname: Goy
authors.forename: John
authors.initials: J
authors.lastname: Wright
authors.forename: Barbara
authors.initials: B
authors.lastname: MacGregor-Cortelli
authors.forename: Ellen
authors.initials: E
authors.lastname: Neylon
authors.forename: Mithat
authors.initials: M
authors.lastname: Gonen
authors.forename: Dixie
authors.initials: D
authors.lastname: Esseltine
authors.forename: Anthony
authors.initials: A
authors.lastname: Boral
authors.forename: David
authors.initials: D
authors.lastname: Schenkein
authors.forename: Klaus
authors.initials: K
authors.lastname: Busam
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Dana
authors.initials: D
authors.lastname: Sachs
authors.forename: Owen A
authors.initials: OA
authors.lastname: O'Connor
mesh_terms: D000368:Aged; D001897:Boronic Acids / Q000009:adverse effects* / Q000627:therapeutic use; D000069286:Bortezomib; D004342:Drug Hypersensitivity / Q000473:pathology; D005260:Female; D006801:Humans; D016015:Logistic Models; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011480:Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D011719:Pyrazines / Q000009:adverse effects* / Q000627:therapeutic use; D012867:Skin / Q000473:pathology; D017445:Skin Diseases, Vascular / Q000139:chemically induced* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib