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Updated: Feb 4, 2026

Establishment of a Human Multiple Myeloma Xenograft Model in the Chicken to Study Tumor Growth, Invasion and Angiogenesis
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A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without Bortezomib in Subjects with

Jacob P Laubach1,2, Chia-Jen Liu1, Noopur S Raje3

  • 1Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|October 4, 2018
PubMed
Abstract

Insights

Evofosfamide shows clinical activity in relapsed/refractory multiple myeloma, with disease stabilization in over 80% of patients. The recommended dose is 340 mg/m² twice weekly, with or without bortezomib.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Hypoxia in bone marrow is a therapeutic target for multiple myeloma.
  • Evofosfamide is a hypoxia-activated prodrug of a DNA alkylator.

Purpose of the Study:

  • To investigate evofosfamide in combination with dexamethasone, and with bortezomib and dexamethasone in relapsed/refractory multiple myeloma.
  • To determine the maximum tolerated dose (MTD), toxicity, and efficacy of evofosfamide regimens.

Main Methods:

  • Phase I/II study involving 59 patients with heavily pretreated multiple myeloma.
  • Two treatment arms: evofosfamide + dexamethasone, and evofosfamide + bortezomib + dexamethasone.
  • Assessment of MTD, dose-limiting toxicities, adverse events, and response rates.

Main Results:

  • MTD established at 340 mg/m² evofosfamide + dexamethasone; MTD for the triplet regimen was also 340 mg/m² with no dose-limiting toxicity.
  • Common grade ≥3 adverse events included thrombocytopenia, anemia, and neutropenia. Skin toxicity occurred in 71% of patients.
  • Over 80% disease stabilization observed, with a median overall survival of 11.2 months.

Conclusions:

  • Evofosfamide can be safely administered at 340 mg/m² twice weekly with or without bortezomib.
  • Clinical activity was noted in heavily pretreated relapsed/refractory multiple myeloma patients.
  • Evofosfamide represents a promising therapeutic option for this patient population.

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