If you’ve been diagnosed with smoldering multiple myeloma (SMM)—especially if you’ve been told you’re high-risk—you’ve likely wondered: Should I treat my smoldering disease right now, or do I need to wait until it’s active myeloma?
This question was at the heart of a recent meeting held by the Oncologic Drugs Advisory Committee (ODAC) on May 20. ODAC is a group of experts, most of whom are oncologists, who help the FDA decide whether new cancer treatments should receive FDA approval.
At this meeting, ODAC reviewed whether Darzalex Faspro® (a version of daratumumab given as a quick shot under the skin) should be approved as the first treatment for people with high-risk smoldering myeloma.
During detailed discussions of a key clinical trial (the AQUILA study), the committee heard from clinicians, researchers, and advocates representing the FDA, Johnson & Johnson (the manufacturer of Darzalex Faspro), and the myeloma patient population on whether this new use of Darzalex could be beneficial for patients. Two very important questions drove the conversation:
AQUILA compared two groups of people diagnosed as high-risk SMM: One group received Darzalex Faspro early. The other group was monitored closely but without myeloma treatment.
The results showed that those who had received Darzalex were less likely to progress to active myeloma or die compared to those who didn’t receive any treatment.
So if AQUILA met its goals, why was there even a discussion?
While it’s true that the AQUILA study was properly executed, different concerns were raised at the ODAC meeting about how the results should be interpreted.
Were the patients in AQUILA truly high risk?
This depends. The definition of ‘high risk’ smoldering myeloma has evolved over time, with four different models having been developed the past 20 years. AQUILA did not use the most recent definition of high-risk in its protocol. In fact, by today’s standards, only 40% of patients in the study would be considered high-risk. Therefore, it is likely that many patients in this study were not likely to progress to active myeloma in the first place. This was in fact observed in the AQUILA study, as most patients in the control arm (who did not receive treatment) did not progress to active myeloma within two years.
What about side effects?
Several adverse reactions were associated with taking Darzalex. These included muscle pain, fatigue, diarrhea, sleep disorder, and rash. Above all, infections were twice as high in Darzalex treated patients compared to the control group. These included high grade, severe infections that required hospitalization. Given these side effects, is it worth it for patients to take Darzalex if they may not progress to MM at all?
For patients who testified at the ODAC, they preferred having a choice. Many discussed the stress of living with a smoldering multiple myeloma diagnosis and the empowerment they felt by being able to do something about it by getting treatment. Other patients discussed how their treatment appears to have kept their smoldering myeloma from progressing, and the relief they feel by being able to avoid active myeloma treatments and their potential toxicities.
After reviewing AQUILA results and hearing from doctors and patients, the ODAC voted 6 to 2 that the trial results provided enough evidence to support a favorable benefit-risk profile for Darzalex for patients with high-risk smoldering myeloma.
While this news indicates this ODAC is persuaded by current results, it does not mean the indication is approved by the FDA just yet.
The FDA will continue to analyze these study results and carefully consider the feedback from ODAC before an official decision is made.
In the meantime, more work is needed:
For patients, if you’ve been diagnosed with smoldering myeloma, ask your doctor:
You can also reach out to the MMRF Patient Navigation Center for more information.
