Elotuzumab with lenalidomide and dexamethasone for Japanese patients with relapsed/refractory multiple myeloma: phase 1 study

Int J Hematol. 2017 Mar;105(3):326-334. doi: 10.1007/s12185-016-2138-4. Epub 2016 Nov 15.

Abstract

Elotuzumab is an immunostimulatory monoclonal antibody that binds to SLAMF7, a type-1 transmembrane protein expressed on myeloma and natural killer cells. We report a phase 1 study (NCT01241292) in which we evaluated the safety, efficacy and pharmacokinetics of elotuzumab combined with lenalidomide and dexamethasone in Japanese patients with relapsed/refractory multiple myeloma (RRMM). In 28-day cycles, patients received: elotuzumab (intravenously), lenalidomide (25 mg orally) and weekly dexamethasone (elotuzumab days: 28 mg orally plus 8 mg intravenously; non-elotuzumab days: 40 mg orally). Elotuzumab dose was initially 10 mg/kg (Cohort 1, n = 3) and, if no dose-limiting toxicities (DLTs) occurred, increased to 20 mg/kg (Cohort 2, n = 3). No DLTs occurred in the six patients treated. Maximum (median) durations of study therapy were 36.6 (35.2) months in Cohort 1 and 28.3 (9.2) months in Cohort 2. Leukopenia and lymphopenia were observed in all patients. No adverse events led to treatment discontinuation. Overall response was 83% (n = 5): one complete response, three very good partial responses, one partial response. Three patients are still undergoing treatment, with responses maintained. Expression of SLAMF7 was immunohistochemically detected in all patients. We find that elotuzumab combined with lenalidomide and dexamethasone exhibited acceptable safety/tolerability in Japanese patients with RRMM, with durable efficacy.

Keywords: Elotuzumab; Phase 1; Relapsed/refractory multiple myeloma.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Dexamethasone / administration & dosage
  • Drug Therapy, Combination / methods*
  • Drug Therapy, Combination / standards
  • Female
  • Humans
  • Lenalidomide
  • Leukopenia / chemically induced
  • Lymphopenia / chemically induced
  • Male
  • Middle Aged
  • Multiple Myeloma / complications
  • Multiple Myeloma / drug therapy*
  • Recurrence
  • Salvage Therapy / adverse effects
  • Salvage Therapy / methods*
  • Signaling Lymphocytic Activation Molecule Family / metabolism
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • SLAMF7 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • elotuzumab
  • Thalidomide
  • Dexamethasone
  • Lenalidomide

Associated data

  • ClinicalTrials.gov/NCT01241292