Kenneth H. Shain, MD
The best opportunity to control multiple myeloma long-term is determining how to optimize treatment upfront, explained Kenneth H. Shain, MD, PhD.
Additionally, Shain said that the FDA approval of daratumumab (Darzalex) in combination with bortezomib, melphalan, and prednisone (VMP) may not have a high clinical impact but has opened the door for future approvals with the CD38 inhibitor, which will be a valuable asset moving forward.
In an interview during the 2018 OncLive® State of the Science SummitTM on Hematologic Malignancies, Shain, an assistant member at Moffitt Cancer Center, discussed the evolution of treatment for patients with newly diagnosed multiple myeloma and how physicians are leveraging data with CAR T-cell therapy and minimal residual disease (MRD) negativity to improve outcomes.
OncLive: How has treatment for patients with newly diagnosed multiple myeloma evolved?
Shain: There are certain things that are now standard of care, and new therapies and interventions we can utilize to improve outcomes. There is also the sequencing of therapy in transplant-eligible patients versus more reduced therapy in patients who are ineligible for transplant or high-dose therapy. [It is also important to think about] what maintenance therapy does and how it has changed how well we can take care of our patients in this setting.
What agents have emerged as a standard of care?
We think of lenalidomide, bortezomib, and dexamethasone as the primary triplet therapy of choice. Now, we’re talking about carfilzomib as a new proteasome inhibitor with some very outstanding data looking at response rates. It's a little early to tell if it will replace bortezomib as an upfront therapy. One of the things that we're talking about more is the approval of the first upfront monoclonal antibody therapy: daratumumab in combination with VMP. [Its approval was based on] a very interesting and profound study. Its implications for the United States are a little bit of a question. We don't know what to do with that approval because not many people give VMP in this country.
Where did the push for the approval come from?
The approval for VMP plus daratumumab really revolves around the fact that daratumumab is such an exciting drug. We want to find ways we can start utilizing it in different aspects of myeloma, not just in the relapsed/refractory setting—which is where it was approved previously. Can we show that adding this monoclonal antibody will benefit our patients upfront? That's the power of the study. Again, its direct application to a United States population is very low, but it really opens the door for its utilization. Hopefully, [it enables subsequent approvals of] daratumumab and other combinations that are much more aligned with our current strategy, such as lenalidomide and dexamethasone (Rd), or RVd.
What studies are examining those combinations?
Those studies are ongoing. There is daratumumab plus bortezomib and low-dose dexamethasone (Vd) and daratumumab plus RVd versus Vd. We just finished a phase II trial called the GRIFFIN study. We'll see how the data mature. These are going to be exciting studies to lead the field forward in terms of quadruplet versus triplet therapy. The hope is that we can introduce the fourth drug without a huge amount of toxicity and gain a lot more in terms of response rates, depth of response, and MRD negativity. I want that to translate into longer outcomes and control of disease for our patients.
How do you determine what your optimal sequence is, and how will subsequent approvals impact that?
It's a question we have all been asking as we have all these new therapies. Daratumumab is just one of them. Elotuzumab (Empliciti) and ixazomib (Ninlaro) are therapies that have been introduced in the relapsed setting. How do we continue to utilize these as we move forward from newly diagnosed to relapsed? We have to figure out how to control the disease upfront because that's the best and first time to control the disease long-term.
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