IN SPITE of the high response rates and lack of progression to active disease with the regimens described at the 2018 American Society of Hematology Meeting & Exposition, several myeloma experts interviewed by The ASCO Post said the data do not yet move them to routinely intervene in high-risk smoldering disease, largely because the studies are small and lack controls. Several experts also pointed out that a toxic death occurred (in a diabetic patient on elotuzumab, lenalidomide, and dexamethasone) on study.

Thierry Facon, MD, of the Hospital Claude Huriez in Lille, France, said he cannot embrace data from a phase II uncontrolled study. “Usually when you do a phase II study with one regimen for smoldering myeloma, you’ll show that a few patients might have disease progression, but none will die. In the Ghobrial study, two did die, one from sepsis. That’s the back side of the story. If you want to develop a regimen for smoldering disease, it has to be as safe as possible,” he commented.

His main concern, at this point, would be changing practice based on preliminary findings from a small study. “You have to design a phase III study and show with a control arm that you’re doing better with another treatment.”

Kenneth Shain, MD, PhD, Director of the Myeloma Working Group at Moffitt Cancer Center, Tampa, emphasized that such treatment should only be given in an academic center and on a clinical trial, probably one with an aggressive treatment arm vs a “simple, cost-effective treatment,” he said.

“We still don’t know precisely what ‘smoldering’ is. Although we know what ‘high risk’ might be, we have a number of algorithms defining it, and not all agree. It is important to note that even with smoldering myeloma, patients can have a high disease burden and not require treatment for many years. As such, it’s important to figure out better ways to identify patients with smoldering disease vs those destined to become active [require therapy],” he commented.

Peter M. Voorhees, MD, of the Levine Cancer Institute and Atrium Health in Charlotte, North Carolina, also said he is not yet treating patients with smoldering myeloma outside of a clinical trial, and he is “cautious about interpreting the results” of the current small studies with different eligibility criteria.

“I think it’s a little different for patients with clear evidence of disease evolution over time. For patients with intermediate- to high-risk smoldering myeloma whose M spike or light-chain parameters are continually getting worse over time, I do think a lot of us have lowered our threshold for starting definitive myeloma treatment,” he said. ■

DISCLOSURE: Dr. Facon has served as an advisor/consultant/speaker for Sanofi, Celgene, Janssen, Takeda, Amgen, Karyopharm, and Oncopeptides. Dr. Shain has served as an advisor or consultant for Celgene, Janssen, Takeda, and Bristol-Myers Squibb and has received grant funding from AbbVie. Dr. Voorhees reported financial relationships with Bristol-Myers Squibb, Amgen, Celgene, Novartis, and Janssen.