title: Otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR(™) therapeutic protein, for relapsed or refractory NHL patients.
abstract: CD37 is cell surface tetraspanin present on normal and malignant B cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic. Patients with relapsed or refractory follicular non-Hodgkin lymphoma (FL), mantle cell lymphoma (MCL), or Waldenström's macroglobulinaemia (WM) received otlertuzumab at 20 mg/kg administered intravenously once a week for up to 8 weeks followed by 4 monthly doses. Sixteen patients were treated; median age was 62·5 years (range, 41-81), and median number of prior regimens was 4 (range, 1-7). Twelve patients were refractory to prior treatment, 5 were refractory to rituximab. The mean terminal half-life was 9·5 days. Lymph node reduction of ≥50% by computerized tomography scan measurements was seen in 3 of 12 patients, including one FL patient who had a partial response. One WM patient had a minor response. The most frequent adverse events were neutropenia, fatigue, nausea, thrombocytopenia, diarrhoea, and peripheral oedema; most were grade 1/2. Otlertuzumab treatment appears to have been well tolerated by the patients in this study. Clinical activity was observed in this small heterogeneous cohort of highly refractory, heavily pretreated B-cell non-Hodgkin lymphoma patients. These data suggest that further clinical investigation in non-Hodgkin lymphoma is warranted.
authors.affiliation: Fred Hutchinson Cancer Research Center, University of Washington, Seattle, WA, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Spurgeon
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.forename: Farrukh T
authors.initials: FT
authors.lastname: Awan
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.forename: Mark C
authors.initials: MC
authors.lastname: Lanasa
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Eisenfeld
authors.forename: Scott C
authors.initials: SC
authors.lastname: Stromatt
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology / Q000627:therapeutic use*; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012008:Recurrence; D059470:Tetraspanins / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C059071:CD37 protein, human; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; C547387:TRU 016; D059470:Tetraspanins
keywords: antiCD37; clinical trial; non-Hodgkin Lymphoma; otlertuzumab