Repurposing leflunomide for relapsed/refractory multiple myeloma: a phase 1 study

Abstract

The inexpensive, well-tolerated, immunomodulatory agent leflunomide, used extensively for the treatment of rheumatoid arthritis, has been shown to produce significant activity against multiple myeloma (MM) in pre-clinical studies. We conducted a phase 1 study (clinicaltrials.gov: NCT02509052) of single agent leflunomide in patients with relapsed/refractory MM (≥3 prior therapies). At dose levels 1 and 2 (20 and 40 mg), no dose-limiting toxicities (DLTs) were observed. At dose level 3 (60 mg), one patient experienced elevated alanine aminotransferase; an additional three patients were enrolled at this dose level without further DLTs. Overall, toxicities were infrequent and manageable. Nine out of 11 patients achieved stable disease (SD), two subjects experiencing SD for nearly one year or longer. The tolerable safety profile of leflunomide, combined with a potential disease stabilization, is motivating future studies of leflunomide, in combination with other MM drugs, or as an approach to delay progression of smoldering MM.

Keywords:

• Leflunomide
• clinical trial
• relapsed/refractory
• multiple myeloma

Disclosure statement

MR is on the speaker’s bureau for Celgene and Takeda. JP is a consultant for Gilead. AK is a consultant for Celgene, serves on the speaker’s bureau for Celgene, Amgen, and Takeda, and has stock ownership in Celgene. This work has been presented in part at the 2016 and 2017 meetings of the American Society of Hematology in San Diego and Atlanta, respectively.

Additional information

Funding

This work was supported by the National Institutes of Health Biostatistics and Mathematical Modeling, Analytical Pharmacology, Integrated Genomics and Bioinformatics, and Pathology Cores (under P30 CA033572).