ASH 2016: Thinking Outside the Box in Myeloma with a New Delivery and Target

BY ERIC HANSEN There is a new drug in clinical trials now which uses a totally new mechanism of action to kill myeloma cells.  Right now we have IMIDs, which enhance and mobilize our immune systems to fight myeloma.  Then there are the proteasome inhibitors; and monoclonal antibodies, and CAR-T therapies in the pipeline which target proteins on the surface of myeloma cells.  We really have been fortunate to see all these drugs joining our arsenal which can keep myeloma at bay for years.  But there is still a need for something new, something that kills myeloma cells that may survive these types of treatments.  One possibility is a drug called I-131-CLR1404 which is being tested in Wisconsin with 7 patients who had relapsed after taking both an IMID and a proteasome inhibitor. Researchers found that the membrane on myeloma cells is distinctly different from normal cells (it has unique lipids and other features) and therefore, cells with this membrane can be targeted for treatment.  The current trial uses a new drug delivery method as well, with specific up-take and retention by myeloma cells.  The new drug carries a payload of a molecular radioisotope, iodine-131, into the cell thereby killing it.  In this first small trial all patients achieved stable disease; one had >30% reduction in serum m-protein; and three had >50% reduction in free light chains, according to the abstract of the trial reported at ASH.  The drug  will be going into phase II which is scheduled for early 2017.  For now however, it is very encouraging to see progress ‘outside the box’ which may result in another valuable new treatment.  CLR-131 has orphan drug status and is supported by a grant from the NCI. For information about the trial go to: CLR1404 Clinical Trial