A phase 1, open‐label, dose‐escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma. (4th April 2016)

• Record Type: Journal Article
• Authors: Dunn, Tamara J.; Dinner, Shira; Price, Elizabeth; Coutré, Steven E.; Gotlib, Jason; Hao, Ying; Berube, Caroline; Medeiros, Bruno C.; Liedtke, Michaela
• Is Part Of: British journal of haematology. Volume 173:Number 2(2016)
• Page Start: 253
• Page End: 259
• Publication Date: 2016-04-04
• Subjects: multiple myeloma -- pralatrexate -- bortezomib -- relapsed -- refractory; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.13946
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: 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/m 2 and intravenous bortezomib at a dose of 1·3 mg/m 2 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/m 2 . 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.