A Phase Ib/II Trial of the First-in-Class Anti-CXCR4 Antibody Ulocuplumab in Combination with Lenalidomide or Bortezomib Plus Dexamethasone in Relapsed Multiple Myeloma

Clin Cancer Res. 2020 Jan 15;26(2):344-353. doi: 10.1158/1078-0432.CCR-19-0647. Epub 2019 Oct 31.


Purpose: Ulocuplumab (BMS-936564) is a first-in-class fully human IgG4 monoclonal anti-CXCR4 antibody that inhibits the binding of CXCR4 to CXCL12.

Patients and methods: This phase Ib/II study aimed to determine the safety and tolerability of ulocuplumab alone and in combination with lenalidomide and dexamethasone (Arm A), or bortezomib and dexamethasone (Arm B), in patients with relapsed/refractory multiple myeloma.

Results: Forty-six patients were evaluated (median age, 60 years; range, 53-67). The median number of prior therapies was 3 (range, 1-11), with 70% of subjects having received ≥3. This trial had a dose-escalation and a dose-expansion part. Using a 3+3 design on both arms of the trial, ulocuplumab's dose was escalated to a maximum of 10 mg/kg without reaching MTD. The most common treatment-related adverse events (AE) were neutropenia (13 patients, 43.3%) in Arm A and thrombocytopenia (6 patients, 37.5%) in Arm B. No deaths related to study drugs occurred. The combination of ulocuplumab with lenalidomide and dexamethasone showed a high response rate (PR or better) of 55.2% and a clinical benefit rate of 72.4%, even in patients who had been previously treated with immunomodulatory agents (IMiD).

Conclusions: This study showed that blockade of the CXCR4-CXCL12 axis by ulocuplumab is safe with acceptable AEs and leads to a high response rate in combination with lenalidomide and dexamethasone in patients with relapsed/refractory myeloma, making CXCR4 inhibitors a promising class of antimyeloma drugs that should be further explored in clinical trials.

Publication types

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

MeSH terms

  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bortezomib / administration & dosage
  • Dexamethasone / administration & dosage
  • Humans
  • Lenalidomide / administration & dosage
  • Maximum Tolerated Dose
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / pathology
  • Patient Safety
  • Receptors, CXCR4 / antagonists & inhibitors*
  • Receptors, CXCR4 / immunology
  • Survival Rate
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • CXCR4 protein, human
  • Receptors, CXCR4
  • Bortezomib
  • ulocuplumab
  • Dexamethasone
  • Lenalidomide