title: Resimmune, an anti-CD3ε recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma.
abstract: Resimmune is a second-generation recombinant immunotoxin composed of the catalytic and translocation domains of diphtheria toxin fused to two single chain antibody fragments reactive with the extracellular domain of CD3ε. We gave intravenous infusions of Resimmune 2.5 - 11.25 μg/kg over 15 minutes to 30 patients (25 with cutaneous T-cell lymphoma, 3 with peripheral T-cell lymphoma, 1 with T-cell large granular lymphocytic leukemia and 1 with T-cell prolymphocytic leukemia) in an inter-patient dose escalation trial. The most common adverse events were fever, chills, hypotension, edema, hypoalbuminemia, hypophosphatemia, and transaminasemia. Among the 25 patients with cutaneous T-cell lymphoma, there were nine responses for a response rate of 36% (95% CI, 18%-57%) including four complete remissions (16%, 95% CI, 5%-36%). The durations of the complete remissions were 72+, 72+, 60+ and 38+ months. There were five partial remissions lasting 3, 3, 3+, 6+ and 14 months. Of 17 patients with a modified skin weighted assessment tool score <50, 17 patients with stage IB/IIB, and 11 patients with both a score <50 and stage IB/IIB, nine (53%), eight (47%), and eight (73%) had responses, respectively. Further studies of Resimmune in patients with low tumor burden, stage IB-IIB cutaneous T-cell lymphoma are warranted. This trial is registered at clinicaltrials.gov as #NCT00611208.
authors: University of Texas Southwestern Medical Center, Dallas, TX arthur.frankel@utsouthwestern.edu.
authors: Arthur E
authors: AE
authors: Frankel
authors: Baylor Scott & White Health, Temple, TX.
authors: Jung H
authors: JH
authors: Woo
authors: University of Texas Southwestern Medical Center, Dallas, TX.
authors: Chul
authors: C
authors: Ahn
authors: Yale University School of Medicine, New Haven, CT.
authors: Francine M
authors: FM
authors: Foss
authors: The University of Texas MD Anderson Cancer Center, Houston, TX.
authors: Madeleine
authors: M
authors: Duvic
authors: Angimmune, LLC, Bethesda, MD, USA.
authors: Paul H
authors: PH
authors: Neville
authors: Angimmune, LLC, Bethesda, MD, USA.
authors: David M
authors: DM
authors: Neville
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017252:CD3 Complex / Q000276:immunology*; D015331:Cohort Studies; D004167:Diphtheria Toxin / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000008:administration & dosage* / Q000009:adverse effects; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D007262:Infusions, Intravenous; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction / Q000379:methods; D014652:Vascular Diseases / Q000139:chemically induced; D055815:Young Adult
chemical_list: D017252:CD3 Complex; C115335:CD3E protein, human; D004167:Diphtheria Toxin; D007128:Immunoglobulin Fragments; D000922:Immunotoxins; D011994:Recombinant Proteins