BETH FAIMAN: Welcome to this virtual roundtable about what's new in the administration of multiple myeloma agents, a case-based approach. My name is Beth Faiman, and I'm a nurse practitioner in the department of hematology and medical oncology at the Cleveland Clinic Taussig Cancer Institute. Joining me today for this discussion are two of my colleagues. Donna?
DONNA CATAMERO: Hi, I'm Donna Catamero. I'm the associate director for myeloma translational research, as well as a nurse practitioner at Mount Sinai Hospital in New York City.
FAIMAN: Tiffany?
TIFFANY RICHARDS: I'm Tiffany Richards. I'm a nurse practitioner at MD Anderson Cancer Center in the department of lymphoma-myeloma.
FAIMAN: In this virtual discussion, we'll review several different new therapeutic therapies with different routes of administration for patients with multiple myeloma. Our discussion will begin with an overview of the current treatment recommendations for multiple myeloma. Then, we will explore together the treatment selection of three different patients, including a patient with newly diagnosed disease, and two patients with relapsed disease.
Here on this slide, we have the faculty—Beth Faiman, Tiffany Richards, and Donna Catamero.
Here, I'd like to start with the introduction to the treatment of multiple myeloma. So, multiple myeloma, as you are well aware, is a cancer of the bone marrow plasma cells. There are various stages of multiple myeloma and many tests that are required to accurately diagnose and appropriately monitor disease. Basically, any patient with an abnormal overproduction of one clonal protein or a monoclonal protein can be classified as having at least MGUS. Smoldering and symptomatic myeloma require more monitoring and more laboratory studies to accurately monitor the disease. In terms of the treatment for multiple myeloma, we'll go over that in a few minutes. In terms of the primary treatment, maintenance therapy, and supportive therapies such as bisphosphonates, denosumab, and other supportive care.
As I mentioned on the previous slide, patients with multiple myeloma can be categorized as having MGUS, which occurs when patients have a low M-protein of less than 3 g/dL, clonal plasma cells greater than 10% in the bone marrow, or sometimes less than 10%, but no end-organ damage or amyloidosis attributed to an underlying disorder.
The second phase is smoldering myeloma. These patients are considered smoldering when they have a higher M-protein concentration in the serum or urine, and the clonal bone marrow plasma cells tend to be between 10% and 60%. But these patients still lack myeloma-defining events. Now we have updated criteria for high-risk smoldering myeloma, called the 22-20 staging system, which takes into account a higher M-protein percentage, a higher serum-free light chain percentage, and a higher bone marrow biopsy percentage. These patients are more likely to progress to requiring treatment for myeloma and should be monitored even closer.
Finally, patients are catapulted into the diagnosis of multiple myeloma if they have a high percentage of clonal bone marrow plasma cells or extramedullary plasma cytoma, and if they have SLiM CRAB criteria. So, again, the SLiM is a bone marrow biopsy of 60% or higher, an elevated light chain kappa-to-lambda ratio greater than 100, and an MRI with greater than one focal lesion. As you recall, the CRAB mnemonic with hypercalcemia, renal insufficiency, anemia, and bone disease, those patients will require emergent therapy and need to be treated ASAP.
In terms of the staging, we first had the Durie Salmon Staging System in the 1970s, and this was revised in the early 2000s for the ISS Staging System. This staging system took into account a serum albumin and a serum beta-2 microglobulin which were thought to be markers of high-risk or low-risk disease. The earlier staging system failed to capture the cytogenetic risk, which is sometimes right now very heavily relied on, and by adding the LDH and adverse FISH genetics, such as translocation 4;14, 14;16, or deletion 17p, those patients confer a particularly poor prognosis if they have single-, double-, or triple-hit disease, meaning they have more adverse genetic abnormalities.
So who is a transplant candidate in myeloma? Well, in many centers, everybody is considered a transplant candidate unless you have lots and lots of comorbid conditions, which might place you at risk for not doing well with that transplant in terms of physical, psychological, or functional status. So, the first step when patients are newly diagnosed is to say, are they fit or are they frail? Do they have sufficient organ function? Advanced age used to be a reason to rule out; however, I know there are patients in my institution well into their 70s who might really want to have that transplant as an option. It's important to refer to a stem cell transplant center to assess for the candidacy and have that discussion, because we know many studies that are ongoing show that transplant will lead to deeper remissions, which is a surrogate marker for overall survival.
When we look at the guidelines from the National Comprehensive Cancer Network, there are differences between the transplant-eligible patients, in whom we like to avoid melphalan that could be toxic to the stem cells, and patients that are transplant-ineligible, in whom those therapies often contain melphalan. We will discuss therapies throughout, so I'll save this discussion for later, but as you can see on this slide, there are so many different options available.
Basically, Category 1 recommendations with the strongest evidence in randomized phase III clinical trials for transplant-eligible patients include bortezomib/len-dex, and then bortezomib/thal-dex, which is used in Europe. We will learn that there are new daratumumab-containing formulations for transplant-eligible patients that are FDA approved in the United States, which we will be hearing about. The transplant-ineligible patients can receive VRd, daratumumab, or any number of combination therapies with the goal to eradicate the plasma cell clone.
So, in terms of follow-up and surveillance, I think it is super important for the practitioner to have the discussion with the patients upfront, that treatment should continue indefinitely. As long as patients are responding to therapy, we will continue therapy to eradicate that stem cell clone in many different situations.
Maintenance therapy in transplant-eligible patients will occur after that stem cell transplant, and it is important to monitor CBC, blood glucose, electrolytes, renal function, liver function, etc., and assess for relapse disease, which is a serial increase of 25% from the lowest absolute measurement of the monoclonal cell. It will also include imaging with CAT scans, MRI, etc.
In terms of treatment for relapsed refractory multiple myeloma, relapsed or progressive disease includes treatment with systemic second-line therapy, perhaps a second stem cell transplant or a stem cell transplant if they have never had one, or participation in a clinical trial.
This next slide highlights current second-line treatments, and as you'll hear from our panelists today, there are different mixing and matching of classes of drugs, which is how we treat myeloma in 2020 and beyond, by using proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies to successfully control the disease.
Category I recommendations in relapsed disease include carfilzomib-based regimens, daratumumab-based regimens, elotuzumab-based regimens, and all oral regimens, including ixazomib, lenalidomide, and dexamethasone.
