A phase 1, open-label, dose-escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma

Tamara J. Dunn, Shira Dinner, Elizabeth Price, Steven E. Coutré, Jason Gotlib, Ying Hao, Caroline Berube, Bruno C. Medeiros, Michaela Liedtke*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used. Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m2 and intravenous bortezomib at a dose of 1·3 mg/m2 on days 1, 8 and 15 of each 4-week cycle. Eleven patients were enrolled and completed a median of two cycles. The maximum tolerated dose was 20 mg/m2. Two patients experienced dose-limiting toxicity of mucositis. The most frequent non-haematological toxicities were fatigue (55%) and mucositis (45%). There were three serious adverse events in three patients: rash, sepsis and hypotension. One patient (9%) had a very good partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and two (18%) had progressive disease. The median duration of response was 4 months, the median time to next treatment was 3·4 months and the median time to progression was 4 months. Pralatrexate, in combination with bortezomib, was generally safe and demonstrated modest activity in relapsed or refractory multiple myeloma. Clinicaltrials.gov identifier: NCT01114282.

Original languageEnglish (US)
Pages (from-to)253-259
Number of pages7
JournalBritish Journal of Haematology
Volume173
Issue number2
DOIs
StatePublished - Apr 1 2016

Keywords

  • Bortezomib
  • Multiple myeloma
  • Pralatrexate
  • Refractory
  • Relapsed

ASJC Scopus subject areas

  • Hematology

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