Peter Voorhees, MD
Triplet regimens have become the preeminent means of treatment for patients with relapsed multiple myeloma, and Peter Voorhees, MD, explained that the results of the phase III OPTIMISMM trial of bortezomib (Velcade) and dexamethasone with or without pomalidomide (Pomalyst) may give physicians yet another 3-drug regimen to use in earlier lines of therapy.
As the landscape continues to evolve, Voorhees said that physicians “need to refine the definition of high-risk disease, and in particular, better identify those patients who have ultra–high-risk disease.”
Additionally, Voorhees noted that the phase III trials that resulted in FDA-approved triplet therapies examined a very heterogeneous group of patients. He said more focus needs to be placed specifically on patients with high-risk cytogenetic subtypes.
“It’s hard to make clear, concrete conclusions when you're just looking at a very small population of the overall group,” said Voorhees, a physician at Levine Cancer Institute and an associate professor in the School of Medicine at University of North Carolina-Chapel Hill.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Voorhees discussed treatments for patients with early relapsed multiple myeloma and previewed future research efforts.
OncLive: Please provide an overview of your presentation.
: I spoke about treatment options for patients with early relapsed multiple myeloma, and by early relapse I mean patients in first- or second- relapse who require second- and third- line therapy. There are more available options for patients with relapsed multiple myeloma than there have ever been.
At this point, it's very clear that, just like in the frontline setting, triplet therapies consistently outperform doublet therapies. The perfect example of this are the lenalidomide (Revlimid) and dexamethasone triplets which include either ixazomib (Ninlaro), elotuzumab (Empliciti), daratumumab (Darzalex) or carfilzomib (Kyprolis). The third agent uniformly improves response rate, depth of response, and progression-free survival (PFS).
Now, we have more mature data showing an overall survival signal in the ASPIRE trial. The other thing that is important to recognize is that while it's important to avoid toxicity in frail patients, the monoclonal antibodies—in particular elotuzumab and daratumumab—are very easily added to backbone doublets of lenalidomide and dexamethasone. As such, many of our frail patients who we would typically reserve doublets for may be perfectly appropriate candidates for triplets in particular situations.
One of the challenges in the United States is that patients are typically on a lenalidomide-based therapy until disease progression as part of their first-line therapy, so a lot of these lenalidomide/dexamethasone regimens don’t pertain to that group of patients. In other words, those patients would have never been eligible for any of those phase III trials. There are a number of non–lenalidomide-based platforms, specifically carfilzomib and dexamethasone as a doublet; I [might give] bortezomib and dexamethasone. Daratumumab with bortezomib and dexamethasone outperforms bortezomib and dexamethasone, so those are certainly reasonable options.
Also, we are going to see an increase in the use of pomalidomide-based therapy in earlier lines of therapy. Mayo Clinic and Dana-Farber Cancer Institute presented very impressive results from phase I/II studies of pomalidomide, bortezomib, and dexamethasone. The phase III OPTIMISMM trial looked at bortezomib and dexamethasone with or without pomalidomide. We don't have the results of that at this point, but there was a press release a number of months ago demonstrating that it had met its primary endpoint of PFS. We're cautiously optimistic that pomalidomide, bortezomib, and dexamethasone will be yet another triplet that we can use in earlier lines of therapy for relapsed patients.
Do a high percentage of patients experience early relapse?
When I talk about early relapse, I'm talking about patients who are progressing either for the first time and need a second-line therapy, or are progressing for the second time and need a third-line therapy. Then, there are the patients who have a short remission following their initial therapy.