Have a Cocktail: Using Multiple Drugs to Treat Myeloma

Cocktails of three, four or even five drugs of various classes are turning myeloma into a chronic condition.
“We can test patients at baseline, and then see how their disease changes over time. We’re learning that multiple myeloma cells have many mutations that vary from patient to patient,” explains Brian Durie, M.D., chairman of the IMF. “We’re characterizing disease at the cellular level. We’re developing tests than can detect just a few multiple myeloma cells, one myeloma cell in a million, what we call ‘minimal residual disease.’”


Meanwhile, research teams around the world are looking at completely new ways to kill myeloma:

Selinexor targets nucleotide transport, what goes in and out of myeloma cells. Based on promising early results, trials of this agent are being expanded.

CB-5083, an oral drug in very early trials, inhibits p97, a protein that acts like a pump, carrying loads of unfolded proteins of each cell. In their frenzied growth, cancer cells create a lot of these botched proteins, which could interfere with the cell’s functions if not removed. By interfering with the pump, it’s hoped that the drug will kill the myeloma cells.

Filanesib (ARRY-520) interferes with “kinesin spindle proteins” which are essential when cells divide. Obviously, messing with a cancer cell’s ability to divide is a good thing.

Ibrutinib inhibits “Bruton’s tyrosine kinsase” (BTK), interfering with the cell signaling pathways of myeloma cells, hopefully accelerating their demise.

In research that experts caution is still in very early stages, some teams are focusing on CAR-T cells, essentially engineering certain immune system T-cells to attack cancer cells.

“There are a lot of good, new drugs in trials now,” Berenson says. “I used to say, ‘Don’t go on a trial until it’s time for the Hail Mary pass.’ Now, we are enrolling many new patients on trials.

“Increasingly, in our studies, we’re trying to capture patients that have really aggressive disease, designing drugs and combinations to treat those patients,” says Shaji Kumar, M.D., of the Mayo Clinic in Minnesota, who has conducted numerous studies on oral proteasome inhibitors for multiple myeloma. “For the patients, the key thing is this: We have made this a chronic disease. Having enough drugs to keep the myeloma under control is the key thing. The longer we keep someone on a drug, the closer they are to something new that might be on the horizon, something that might cure this disease. Our next goal is to start exploring the possibility of a cure for the disease. This will eventually come from the judicious combinations of the effective drugs we have been blessed with, as well as determining the right time to intervene.”

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