Otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR(™) therapeutic protein, for relapsed or refractory NHL patients

Br J Haematol. 2015 Jan;168(1):38-45. doi: 10.1111/bjh.13099. Epub 2014 Aug 22.

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.

Keywords: antiCD37; clinical trial; non-Hodgkin Lymphoma; otlertuzumab.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use*
  • Lymphoma, Non-Hodgkin / diagnosis
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Lymphoma, Non-Hodgkin / pathology*
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / therapeutic use*
  • Recurrence
  • Tetraspanins / antagonists & inhibitors
  • Treatment Outcome

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • CD37 protein, human
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • TRU 016
  • Tetraspanins