A solvent used extensively for both industrial as well as pharma­ceutical pur­poses may have substantial anti-myeloma activity.

This is the conclusion of a recent study by an international team of re­searchers, which carried out a wide range of pre-clinical investigations of the solvent N-methyl-2-pyrrolidone (NMP).

The scientists looked at the effect of NMP on myeloma cells in laboratory cul­tures as well as in mice implanted with myeloma cells. Their testing indicates that safe doses of NMP may have anti-myeloma activity com­pa­ra­ble to – if not better than – Revlimid ^[1] (lena­lidomide).

The research team that investigated NMP's anti-myeloma activity was led by scientists from the Peter MacCallum Cancer Centre in Melbourne, Australia.  It also included researchers from the Mayo Clinic in Scottsdale, Arizona, and several additional cancer centers in Australia and New Zealand.

NMP’s activity against multiple myeloma appears to be the result of two separate but complementary pro­cesses.

First, in a manner similar to the "immunomodulatory" drugs Rev­limid and thalidomide ^[2] (Thalomid), NMP makes the body’s own immune system more effective in fighting multiple myeloma.

Second, NMP also affects processes within myeloma cells that allow them to survive. In this regard, NMP functions similarly to a class of drugs known as bromodomain inhibitors. These drugs, which include the compound JQ1, have attracted attention in recent years as potential treatments for a range of different cancers, including multiple myeloma.

NMP, however, may be active against myeloma cells that have developed resistance to drugs such as Revlimid and thalidomide.  This is because mechanisms known to create resistance to existing im­muno­modu­la­tory myeloma therapies do not seem to play a role in NMP’s anti-myeloma activity.

NMP’s potential as a myeloma treatment was first noticed several years ago by Australian researchers. While testing other potential anti-myeloma therapies that had been dissolved in NMP, the scientists ob­served that the solvent, on its own, seemed to counteract myeloma cells.

NMP is currently used in a variety of different ways. It can be found in nail polish remover, paint stripper, patches to deliver drugs through the skin, orthopedic cements (including cements used for vertebroplasty ^[3]), and as a solvent for injected drugs.

Although NMP is considered to be relatively safe at commonly used concentrations and exposure levels, it is listed by the state of California as having “reproductive toxicity.”

Because NMP is already widely produced, it has the potential to be not only a new myeloma therapy, but also an inexpensive new myeloma therapy.

The authors of the current study plan to start a phase 1 clinical trial of NMP in up to 30 Australian multiple myeloma patients later this year.  Funding for the trial has been secured from Australia's National Health and Medical Research Council after peer-review of a funding proposal.

Even if NMP performs well in its initial clinical trial involving multiple myeloma patients, it would still need to undergo additional clinical trials to confirm both its safety and efficacy. These trials are required before an application could be filed with regulatory authorities – such as  the U.S. Food and Drug Administration (FDA) – for permission to sell the drug for use outside of clinical trials.

Overall, it typically takes more than five years for a cancer drug to go from its initial clinical trials to final reg­u­latory approval.  In the case of Kyprolis ^[4] (carfilzomib), for example, FDA approval occurred almost seven years after the start of the drug's first clinical trial.

For more information about the NMP study, please refer to Shortt, J., et al., “The drug vehicle and solvent N-methyl­pyr­rol­i­done is an immunomodulator and antimyeloma compound,” Cell Reports, 2014, dx.doi.org/10.1016/j.celrep.2014.04.008 (full text ^[5]).