Revlimid Reduces Risk of Smoldering Multiple Myeloma Progressing Into Cancer

Using Revlimid (lenalidomide) as a preventative treatment for smoldering multiple myeloma significantly reduced the risk for the precursor disease to progress into cancer, compared with just observation, according to findings from the phase 2/3 E3A06 trial to be presented at the 2019 ASCO Annual Meeting.

Smoldering multiple myeloma is an early precursor to multiple myeloma and produces certain proteins — measured in the blood and urine – that show up before a person has any symptoms of the disease. Since, most people with smoldering multiple myeloma eventually develop myeloma, the current strategy is to monitor these patients.

“We typically see two types of patients — those who are anxious and want to do something to prevent cancer from developing, and those who are more cautious and are willing to watch and wait,” lead study author Dr. Sagar Lonial, chief medical officer at Winship Cancer Institute of Emory University in Atlanta, said in a press release. “It’s gratifying to know that especially for the first group of patients there may now be a viable treatment option.”

In the randomized phase 2/3 trial, led by the ECOG-ACRIN Cancer Research Group and sponsored by the National Cancer Institute, the researchers evaluated the efficacy and safety of Revlimid compared with observation in patients with asymptomatic high-risk smoldering multiple myeloma to determine the reduction in risk and two-year progression-free survival (the time from treatment to disease progression).

At three years of follow-up, in 87% (phase 2) and 91% (phase 3) of patients with smoldering multiple myeloma who received Revlimid, the condition did not progress to cancer compared with 66% of people who underwent observation (phase 3).

Overall, Revlimid induced a 72% reduction in the risk for progression to symptomatic disease. Moreover, the time to develop multiple myeloma was delayed with the agent compared with observation.

While the researchers found a 72% reduction in the risk for progression of smoldering multiple myeloma to symptomatic disease with organ damage, they also discovered this benefit was consistent across low, intermediate and high-risk groups — highlighting the potential for future study.

“What is really quite interesting is that each group appeared to benefit almost equally with early intervention with lenalidomide as a single agent, suggesting that while the high-risk group may be the group that we target now, this may be a fertile area for further investigation in the intermediate-risk group as well, which no trial has ever demonstrated benefit for the prevention of smoldering (disease) from developing into symptomatic myeloma,” Lonial said during a presscast held ahead of the meeting.

In addition, he noted that about 50% of patients had an objective response to Revlimid in both the phase 2 and phase 3 trial. Moreover, in the phase 2 portion of the study, 78% of the 44 patients enrolled did not progress to myeloma, with a median follow-up of over five years.

“With a similar-risk group of patients, one would expect that 50% to 60% of those patients would have converted to myeloma in that same time frame, suggesting that we would have prevented the development of organ damage and symptomatic myeloma in a large fraction of patients — not just in the randomized trial, but also in the smaller portion – and that is occurring with just some (side effects),” he added.

Side effects included low white blood cell count, infections, dermatologic/skin effects, shortness of breath, fatigue, hypertension and low potassium levels.

“It is pretty clear that many of us would argue that early intervention with a prevention strategy — not a treatment strategy – can reduce the risk of conversion to symptomatic myeloma,” Lonial concluded.

Multiple myeloma expert Dr. Joshua Richter, an assistant professor of medicine at The Tisch Cancer Institute at Mount Sinai in New York City, agreed, highlighting the importance of these trial findings.

"The majority of patients with smoldering disease in this country are followed with observation alone with a small percentage enrolling into interventional clinical trials. The findings of this study support an improvement in progression free survival with an acceptable toxicity profile."

In addition, ASCO president Dr. Monica M. Bertagnolli, applauded the researchers’ efforts. “Living with the uncertainty of whether cancer will develop is very difficult, so it’s exciting to be able to tell patients at high risk of multiple myeloma that they can take a pill to prevent or delay cancer,” she said. “This approach is not for everyone, however, because it comes with potentially heavy side effects and costs, so watching and waiting still has clear advantages that every patient should discuss with their doctor.”