Randomized phase 2 study of otlertuzumab and bendamustine versus bendamustine in patients with relapsed chronic lymphocytic leukaemia

Br J Haematol. 2017 Feb;176(4):618-628. doi: 10.1111/bjh.14464. Epub 2016 Dec 15.

Abstract

Otlertuzumab (TRU-016) is a humanized anti-CD37 protein therapeutic that triggers direct caspase-independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles and IV bendamustine (70 mg/m2 ) on Days 1 and 2 of each cycle for up to six 28-day cycles or bendamustine alone. Thirty-two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone. Overall response rate according to the International Workshop on Chronic Lymphocytic Leukaemia criteria was 69% in the otlertuzumab and bendamustine arm and 39% in the bendamustine alone arm (P = 0·025). Median progression-free survival (PFS) was 15·9 months in the otlertuzumab and bendamustine arm and 10·2 months in the bendamustine alone arm (P = 0·0192). There was a higher incidence of pyrexia (34% vs. 12%) and neutropenia (59% vs. 39%) with the combination but this did not result in a higher incidence of severe (grade 3/4) infections (13% vs. 27%). This combination significantly increased the response rate and prolonged the PFS over single agent bendamustine in patients with relapsed or refractory CLL.

Keywords: CLL; bendamustine; otlertuzumab.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Alkylating
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bendamustine Hydrochloride / administration & dosage*
  • Bendamustine Hydrochloride / therapeutic use
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Fever / chemically induced
  • Humans
  • Immunoglobulin G / administration & dosage*
  • Immunoglobulin G / therapeutic use
  • Leukemia, Lymphocytic, Chronic, B-Cell / complications
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Male
  • Middle Aged
  • Neutropenia / chemically induced
  • Recombinant Fusion Proteins / administration & dosage*
  • Recombinant Fusion Proteins / therapeutic use
  • Recurrence
  • Remission Induction
  • Salvage Therapy / adverse effects
  • Salvage Therapy / methods

Substances

  • Antineoplastic Agents, Alkylating
  • Immunoglobulin G
  • Recombinant Fusion Proteins
  • TRU 016
  • Bendamustine Hydrochloride