Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma

Br J Haematol. 2016 Nov;175(3):448-456. doi: 10.1111/bjh.14263. Epub 2016 Jul 19.

Abstract

Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM.

Keywords: elotuzumab; multiple myeloma; relapsed/refractory; signalling lymphocytic activation molecule family member 7; thalidomide.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Dexamethasone / administration & dosage
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / mortality
  • Multiple Myeloma / pathology*
  • Neoplasm Staging
  • Recurrence
  • Retreatment
  • Survival Analysis
  • Thalidomide / administration & dosage
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • elotuzumab
  • Thalidomide
  • Dexamethasone