April 30, 2014

Potential mechanism for myeloma drug’s variable toxicity

A genetic variant is associated with toxicity of the chemotherapy drug melphalan, and could guide individualized dosing for the medication.


The chemotherapy drug melphalan is a standard treatment for multiple myeloma – particularly in high doses with autologous stem cell transplantation (ASCT). Dose-limiting toxicities of melphalan include myelosuppression and gastrointestinal injury, but the occurrence and severity of these side effects vary between individuals.

Stephen Brandt, M.D., and colleagues investigated whether genetic variation in the transporters that ferry melphalan into cells contributes to inter-individual differences in gastrointestinal complications. They analyzed genetic variation in two transporter genes (SLC7A5 and SLC7A8) in 135 patients with multiple myeloma who were all treated with high-dose melphalan and ASCT, and compared genetic variation to the need for total parenteral nutrition (intravenous feeding suggesting gastrointestinal injury).

The investigators found an association between a single change in SLC7A5 and the need for total parenteral nutrition. The results, published in Biology of Blood and Marrow Transplantation, suggest that variability in transport of melphalan into cells impacts mucosal injury after high-dose treatment and could help individualize melphalan dose.

This research was supported by CTSA award TR000445 from the National Center for Advancing Translational Sciences of the National Institutes of Health.

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