VIDEO: 'Guiding principles' to help navigate multiple myeloma treatment landscape

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I think it's extremely important to keep in mind that because of the many, many treatment options available, myeloma treatment has become more of a — I would say — an art. Although I think that's a misnomer because a lot of times that means that people think that they can kind of modify the treatment in a lot of different ways.

I think in my mind, personally, there are two or three guiding principles that I really keep in mind. Number one, to be able to create the best possible outcome or mimic the results of a clinical trial based on which I'm using a drug, I need to try to recreate that clinical trial's criteria. So, whoever qualified for that trial, how the treatment was given, the regimen, the schedule. If I can recreate that thing, I can expect that the patient is going to derive the maximal benefit out of that. So that is one guiding principle — try to stick to the clinical trial recipe.

But when it comes to sequencing treatment or navigating the landscape, I broadly consider three groups of factors, and take them into account to come up with a decision for that patient at that time. And number one would be patient-related factors. What is the age? What is the comorbidity? What are the sociodemographic factors that decide whether or not they can come to treatment frequently? Patient preferences, their goals of treatment, caregiver support, etc. So patient characteristics. What are the comorbidities? For example, also with them, any side effects that are still lingering from the previous treatments, neuropathy, diarrhea, whatever. So, all of that has to be kept into mind about the next treatment option.

The second group of factors is disease-related factors. Was it high risk? What all treatments have been given before? Did the patient respond to them or not? Is it just a biochemical progression happening? Is it a clinical progression happening? Is there any major myeloma related event happening that we need to treat urgently — kidney failure, fractures, hypercalcemia, etc? So that's disease-related factors. And then treatment-related factors, which would be, what are the side effect profile of the drugs? What's an IV drug, subcutaneous, oral only? Again, taking into account patient preferences and also the benefit lined up. When we put all of this together, like I said, we try to take the right decision for the right patient at the right time.

Another kind of important guiding principle is, in my mind, BCMA-targeted therapy is a standard of care. Every patient must get at least one legitimate shot at a BCMA-targeting therapy, and sometimes even more than one. We have many, many patients who are going after — we're going after BCMA with different agents. Another very important thing to consider — I'm a huge proponent of clinical trials. If there is a clinical trial option available, patients should be aware of that. So that said, we are always trying that our traditional agents like the proteasome inhibitors, the [immunomodulatory agents (IMiDs)], the monoclonal antibodies, CD38 monoclonal antibodies, they are best given as triplet regimens. Those triplet regimens should be continued for as long as possible. The dexamethasone typically stops providing additional benefit after 8, 10, 12 months. And then somewhere about a year or so mark, the patients can go to some kind of a maintenance kind of a schedule. And those regimens should be continued for as long as they benefit the patient. Generally after four lines of therapies, when CAR-T and bispecific antibodies are available. CAR-T tends to provide more benefit when it is given in a BCMA-naive setting — means the patient has not had a prior BCMA therapy.

So, if they are a candidate for CAR-T, CAR-T should be their first BCMA-targeting drug. And then subsequently they could get to, we talked about talquetamab, which is a GPRC5D-targeting agent. Or they could again go to BCMA-targeting agent with teclistamab or elranatamab. Selinexor [Xpovio, Karyopharm Therapeutics] is used every now and then in different combinations. We prefer to use selinexor with proteasome inhibitors. It's side effect profile is a little bit tricky. But when we use appropriate, supportive care can be used and we tend to use a lower dose and a weekly regimen. So, these are kind of just some guiding principles, I would say. I don't think one size fits all. But when we take these guiding principles into account, again, I would say we're trying to come up always with the right decision for the right patient at the right time.