title: Clinical efficacy of zanolimumab (HuMax-CD4): two phase 2 studies in refractory cutaneous T-cell lymphoma.
abstract: The efficacy and safety of zanolimumab in patients with refractory cutaneous T-cell lymphoma (CTCL) have been assessed in two phase 2, multicenter, prospective, open-label, uncontrolled clinical studies. Patients with treatment refractory CD4(+) CTCL (mycosis fungoides [MF], n = 38; Sézary syndrome [SS], n = 9) received 17 weekly infusions of zanolimumab (early-stage patients, 280 and 560 mg; advanced-stage patients, 280 and 980 mg). The primary end point was objective response (OR) as assessed by composite assessment of index lesion disease activity score. Secondary end points included physician's global assessment (PGA), time to response, response duration, and time to progression. ORs were recorded for patients in both CTCL types (MF, 13 ORs; SS, 2 ORs). In the high-dose groups (560 and 980 mg dose groups), a response rate of 56% was obtained with a median response of 81 weeks. Adverse events reported most frequently included low-grade infections and eczematous dermatitis. Zanolimumab showed marked clinical efficacy in the treatment of patients with refractory MF, with early onset of response, high response rate, and durable responses. The treatment was well tolerated with no dose-related toxicity other than the targeted depletion of peripheral T cells. A pivotal study has been initiated based on these findings.
authors.affiliation: Multidisciplinary Cutaneous Lymphoma Program, Stanford Comprehensive Cancer Center, 875 Blake Wilbur Drive, Stanford, CA 94305, USA. younkim@stanford.edu
authors.forename: Youn H
authors.initials: YH
authors.lastname: Kim
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
authors.forename: Erik
authors.initials: E
authors.lastname: Obitz
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
authors.forename: Lars
authors.initials: L
authors.lastname: Iversen
authors.forename: Anders
authors.initials: A
authors.lastname: Osterborg
authors.forename: Sean
authors.initials: S
authors.lastname: Whittaker
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Illidge
authors.forename: Thomas
authors.initials: T
authors.lastname: Schwarz
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.forename: Kevin
authors.initials: K
authors.lastname: Cooper
authors.forename: Kim M
authors.initials: KM
authors.lastname: Knudsen
authors.forename: Steen
authors.initials: S
authors.lastname: Lisby
authors.forename: Ole
authors.initials: O
authors.lastname: Baadsgaard
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015704:CD4 Antigens / Q000737:chemistry*; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016410:Lymphoma, T-Cell, Cutaneous / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000628:therapy; D011446:Prospective Studies; D012751:Sezary Syndrome / Q000628:therapy; D012878:Skin Neoplasms / Q000628:therapy*
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015704:CD4 Antigens; C520522:zanolimumab