A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events

Swaminathan P. Iyer, Joseph Taddeus Beck, Alexander Keith Stewart, Jatin Shah, Kevin R. Kelly, Randi Isaacs, Sanela Bilic, Suman Sen, Nikhil C. Munshi

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

Dickkopf-1 (DKK1), expressed by myeloma cells, suppresses osteoblast function and plays a key role in bone disease in multiple myeloma. BHQ880, a human neutralizing IgG1 anti-DKK1 monoclonal antibody, is being investigated for its impact on multiple myeloma-related bone disease and as an agent with potential anti-myeloma activity. The primary objectives of this Phase IB study were to determine the maximum tolerated dose (MTD) of BHQ880 and to characterize the dose-limiting toxicity (DLT) of escalating doses in combination with anti-myeloma therapy and zoledronic acid. Twenty-eight patients were enrolled and received BHQ880 at doses of 3-40 mg/kg. No DLTs were reported, therefore, the MTD was not determined. The recommended Phase II dose was declared as 10 mg/kg, based mainly on saturation data. There was a general trend towards increased bone mineral density (BMD) observed over time; specific increases in spine BMD from Cycle 12 onwards irrespective of new skeletal-related events on study were observed, and increases in bone strength at the spine and hip were also demonstrated in some patients. BHQ880 in combination with zoledronic acid and anti-myeloma therapy was well tolerated and demonstrated potential clinical activity in patients with relapsed or refractory multiple myeloma.

Original languageEnglish (US)
Pages (from-to)366-375
Number of pages10
JournalBritish Journal of Haematology
Volume167
Issue number3
DOIs
StatePublished - Nov 1 2014

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zoledronic acid
Multiple Myeloma
Maximum Tolerated Dose
Bone Diseases
Bone Density
Spine
Therapeutics
Osteoblasts
Hip
Immunoglobulin G
Monoclonal Antibodies
Bone and Bones
BHQ880

Keywords

  • BHQ880
  • Multiple myeloma
  • Phase I
  • Skeletal-related event

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

Cite this

A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events. / Iyer, Swaminathan P.; Beck, Joseph Taddeus; Stewart, Alexander Keith; Shah, Jatin; Kelly, Kevin R.; Isaacs, Randi; Bilic, Sanela; Sen, Suman; Munshi, Nikhil C.

In: British Journal of Haematology, Vol. 167, No. 3, 01.11.2014, p. 366-375.

Research output: Contribution to journalArticle

Iyer, Swaminathan P. ; Beck, Joseph Taddeus ; Stewart, Alexander Keith ; Shah, Jatin ; Kelly, Kevin R. ; Isaacs, Randi ; Bilic, Sanela ; Sen, Suman ; Munshi, Nikhil C. / A Phase IB multicentre dose-determination study of BHQ880 in combination with anti-myeloma therapy and zoledronic acid in patients with relapsed or refractory multiple myeloma and prior skeletal-related events. In: British Journal of Haematology. 2014 ; Vol. 167, No. 3. pp. 366-375.
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