This section called “CME Corner,” highlights, when available, relevant continuing medical education (CME) opportunities deemed to be of use to readers. Articles include an overview of a specific area where key opinion leaders have determined there to be an educational need and a link to the available CME program.
The CME program titled "Updates on Treatment Approaches Across the Multiple Myeloma Spectrum" is currently available on this topic until April 30, 2020.
The important thing when talking about relapse or refractory myeloma is to define, in large part, two things: (1) whether it is an early relapse or a first or second relapse; and (2) whether the individual is truly refractory, that is, are they relapsing while on therapy, even maintenance therapy?
There is no single standard of care. There are currently seven regimens that have been studied that led to Food and Drug Administration-approved agents in that exact space. There are many options in that first or second relapse space without head-to-head comparison of all of these different treatments.
For those patients who are relapsing, who are not currently on maintenance lenalidomide and not currently on treatment with lenalidomide, then the therapy that we typically would use is a combination of daratumumab, lenalidomide, and dexamethasone.
For those patients who are on lenalidomide as maintenance, our most common regimen is to use the combination of daratumumab, pomalidomide, and dexamethasone.
Pomalidomide is in the same class of medications as lenalidomide and works when lenalidomide does not work. Now, the clinical trial data for this combination is after two relapses, but in our daily practice we have moved this up to first relapse, particularly in those patients progressing on lenalidomide maintenance.
That is one option, but another very reasonable option, if a patient has not been on lenalidomide maintenance, is to do a combination of carfilzomib, lenalidomide, and dexamethasone—also a very active therapy—and then consider using a daratumumab regimen at the subsequent relapse.
If we use daratumumab at the first relapse, then often we will be using carfilzomib at the second relapse. In myeloma, none of these therapies, once the patients relapse, are curative. In large part, we are going to be using several combinations. Whether we use a combination is not really an “if” question; it is more of a “when” question.
Patient Factors
In terms of individual patient factors that must be considered when determining an approach, we consider the therapy they are currently on. The other thing that we will consider is the aggressiveness or the pace of disease. If a patient has a very aggressive disease, then you certainly want to do these therapies that have the highest response rates.
If a patient has more of an indolent progression, then you can choose a regimen that maybe has a little bit lower response rate overall but is more convenient from a dosing strategy. For example, using the combination of ixazomib, lenalidomide, dexamethasone—an all oral regimen. While, again, you cannot really compare studies because they are different patient populations, it appears that the overall response rate is lower. But in a patient who has a slower indolent relapse without high-risk features, you can consider a more convenient regimen before doing the more infusions that involve coming to the hospital or coming to the clinic.
Treatment in the Maintenance Setting
When we think about maintenance strategies, you have to divide patients before making decisions. First, you want to consider whether the patient has had a transplant or not. Then you want to think about risk status, ie, high risk or not high risk. In patients who have had a transplant and standard risk disease—independent of what induction therapy is—the standard is single-agent lenalidomide, which has shown to be very effective. There is debate within the field about whether to use continuous dosing of lenalidomide or to use 3 weeks on, 1 week off. Our approach, in general, is the latter. That dosing is associated with somewhat better tolerance and similar long-term benefits.
The other question that remains open in the field is the length of time to be on maintenance therapy. The original US studies showed positive outcomes, including the benefit of overall survival and treatment of lenalidomide to progression. Other people have had a limited time use of lenalidomide to one, two, or three years.
Now, the following question has emerged: “Could we use things like minimal residual disease status to help us to find the length of time that is appropriate for maintenance therapy?” In our high-risk patients, there has been a long history of positive data using bortezomib, particularly in patients with deletion 17p, as well as those patients with renal insufficiency. We incorporate bortezomib as part of our maintenance approach post transplant, again, using a combination of lenalidomide and bortezomib as a post-transplant strategy. When we think about maintenance or ongoing therapy in the nontransplant candidate, we use a slightly different approach because the nontransplant candidates do not have what I would call a “sentinel event” that defines the time at which you would end the initial therapy and think about maintenance.
A very good study was recently presented that showed that, in patients who started out with lenalidomide and dexamethasone after 9 months of len/dex, switching len maintenance alone was associated with good outcomes. I think that is a very reasonable approach.
Standardizing Evidence-Based Care at Winship Cancer Center
Our myeloma team meets regularly to discuss treatments, and twice a year we sit down to specifically create what I would call pathways. It is a multidisciplinary team with nurses, doctors, pharmacists, advance practice providers.
For newly diagnosed, high-risk transplant patients, we discuss what our treatment should be and then create a plan that everyone can use. Now, just because we have created a plan, does not mean that there is not flexibility within that plan or that you cannot treat individual
patients like individuals. We also have a pathway for treating patients in the newly diagnosed setting. It is much easier to create a pathway in the newly diagnosed setting. In the relapse setting, the variables are much larger. Treatment for that becomes more of a standard practice than a clear pathway.
After our team decides on a set pathway, we create a diagram of the pathway. We have published several of these iterations over the years in review articles. Today, those prior publications are likely out of date, but we have a history of publishing these pathways that we use.
Conclusion
It is an exciting time in myeloma. New drugs are being developed. We are still learning how to incorporate technology like minimal residual disease testing and still learning how to individualize therapy based on underlying biology. The large history of myeloma was to treat all myeloma patients the same. Our hope is that we can start to individualize this more, that is, individualize care by having clear biologies that drive plans.
The CME program titled "Updates on Treatment Approaches Across the Multiple Myeloma Spectrum" is currently available on this topic until April 30, 2020.
