Should Physicians Treat Smoldering Multiple Myeloma?

Sagar Lonial, MD, FACP, of the Winship Cancer Institute at Emory University School of Medicine, and Keith Stewart, MBChB, MBA, of the Princess Margaret Cancer Centre, joined Chadi Nabhan, MD, MBA, FACP, host of The HemOnc Pulse, for a conversation on multiple myeloma (MM) treatments and trials at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition.

Drs. Lonial, Stewart, and Nabhan first discussed the plenary session at ASH, which included an abstract on the four-drug regimen of carfilzomib, lenalidomide, and dexamethasone (KRd) plus ixazomib.

Dr. Nabhan asked if there is a particular inhibitor that is superior for treating patients with MM. Dr. Stewart noted that while carfilzomib treatment is extremely effective, there is currently no regulatory approval for the drug in a frontline setting.

“There’s nowhere to use the drug…it feels futile to be doing all these studies without an endpoint,” Dr. Stewart explained.

Dr. Lonial then discussed the Eastern Cooperative Oncology Group trial, which compared KRd with bortezomib-lenalidomide (VRd) and dexamethasone in standard-risk patients with MM and found that progression-free survival was equal between the two treatment groups. Moving forward, they are hoping to see results from a study comparing the two treatment regimens in high-risk MM.

The trio also discussed the PERSEUS phase III trial, which compared daratumumab, VRd, transplant, consolidation, and daratumumab-lenalidomide maintenance with VRd, transplant, consolidation, and lenalidomide maintenance.

“One of the controversial things about the study is there is an assumption that daratumumab is helping…but there’s no randomized trial that proves that point,” said Dr. Stewart.

Finally, Drs. Lonial and Stewart engaged in a discussion about whether there should be a reason to treat smoldering MM.

As Dr. Lonial explained, there are two clinical trials in that setting. “We don’t treat people off study,” he said. “If you can change when a patient develops myeloma, or prevent them from developing myeloma, that’s the endpoint.”

“I don’t treat my smoldering myeloma patients, generally,” Dr. Stewart added. “I still tend to watch them. There are very aggressive attempts to get rid of smoldering myeloma, including KRd and transplant. To me, it wasn’t curing most people. Even if people need treatment in the next two or three years, they’re going to live 10 to 15 years, and the worst thing you can do is cause toxicity and even death.”