Attacking Multiple Myeloma on Multiple Fronts

The inner makeup of myeloma looks like more than one disease.

In recent years, scientists have determined that tumors are a mixture of genetic mutations. A 2012 study in the New England Journal of Medicine, for example, revealed wide genetic variation within a single mass of kidney cancer cells. Now, a recent Cancer Cell study unveils similar genetic complexities in multiple myeloma. Physicians believe the findings can have immediate implications for treatment strategies.

“What this new work shows us is that when we treat an individual patient with multiple myeloma, it’s possible that we’re not just looking at one disease, but at many,” said co-senior author Todd Golub, the Broad Institute’s chief scientific officer and Charles A. Dana investigator in human cancer genetics at the Dana-Farber Cancer Institute, in a press release.

Looking at tumor samples from more than 200 multiple myeloma patients, the researchers found a vast array of the usual suspects of mutations linked to cancer. But several of these mutations were only found in a small percentage of the cells from a given patient.

This study reveals the genetic complexity of multiple myeloma and highlights just how tricky it is to treat. The findings may also help explain why many patients often relapse following successful treatment.

Not everyone is entirely surprised. “We’ve known for several decades that myeloma cells have many chromosomal abnormalities,” said Brian G.M. Durie, MD, on his blog for the International Myeloma Foundation (IMF), noting that the tumors were even more diverse than previously appreciated. But the study underscores for him the need to change tactics in treatment approach.

“The sobering data from this study…,” he said, “demonstrate why the promise of individual therapies targeted against individual genes is fading.”

Such targeted therapies, which seek out specific genetic defects to fight tumor cells, are currently being tested for myeloma. But the new findings suggest they may leave behind other flavors of the tumor cells, changing up the target entirely.

“There’s clearly potential for these drugs in some patients with multiple myeloma, but we show that there are also potential problems for others,” Jens Lohr, MD, PhD, a co-author on the study, said to ASCO Post.

To hit on all these different populations, therapies that attack the disease on multiple fronts have a better chance. And future treatments might revolve around a cocktail—possibly including immune and cellular therapies—delivered simultaneously or sequentially. But more research is still needed. Durie points to the IMF’s Black Swan Research Initiative, which aims to cure myeloma using several approaches that already account for the idea that myeloma is a genetic melting pot.

At least the new findings may have spurred additional interest from scientists who like a challenge. “In a sense, you have different diseases within a patient,” said Mohamad Hussein, vice president of scientific affairs at Celgene. “Everyone realizes myeloma is a very interesting disease. And we are getting closer to understanding its complexities.”