Personalizing Relapsed Multiple Myeloma Therapy: Amandeep Godara, MBBS

Sequencing therapy for relapsed/refractory (R/R) multiple myeloma has become increasingly nuanced as chimeric antigen receptor (CAR) T-cell therapy, bispecific antibodies, and cereblon E3 ligase modulatory drugs (CELMoDs) all compete for use at first relapse, Amandeep Godara, MBBS, of the Huntsman Cancer Institute, highlighted in an interview at a recent Institute for Value-Based Medicine® event in Salt Lake City, Utah.

He told The American Journal of Managed Care^® (AJMC^®) that patient age, comorbidities, distance from treatment centers, and disease burden all factor into treatment decisions. In particular, referral timing, travel distance, caregiver availability, and insurance preferences can delay access to CAR T-cell or bispecific therapies for rural patients. At the same time, Godara noted that clinical experience has allowed for more individualized treatment decisions rather than a fixed algorithm.

This transcript has been lightly edited for clarity.

AJMC: With the treatment landscape for R/R multiple myeloma continuing to expand, what patient- and disease-specific factors most influence how you sequence these therapies?

Godara: This is a burning question in our clinics with all these new therapies becoming available, especially when patients experience this first relapse. The discussion is becoming much more nuanced than it was a few years ago. We have the choice of choosing CAR T-cell therapy or bispecific combinations, and now we have a CELMoD agent that's FDA-approved for treatment of multiple myeloma at the time of first relapse.

The number of options available for somebody to treat at the time of the first relapse has grown quite a bit, and the data that we have available so far do seem to indicate that CAR T-cell therapy and bispecific therapy combinations are probably the most effective therapies out there at the time of these discussions, whenever available.

When it comes to patient considerations, we think about how old our patient is, what kind of other health problems they have alongside multiple myeloma, and how far they live from our center when it comes to thinking about setting up any of these immunotherapies. We think about the disease also in terms of how aggressive this disease relapse is and whether or not this patient has a significant disease burden that we will need to think about bridging therapy if you are going in the direction of CAR T-cell therapy.

Our role, I think, increasingly is to discuss all the options available. We discuss what the most effective therapies are at that line of treatment that we are considering here. We would like our patients to be as aware as possible about how well these therapies could work against multiple myeloma and all the logistical requirements that come around when it comes to using these therapies.

For example, CAR T-cell therapy is going to take some time to be ready. There's a period of time where we collect a patient's T cells, and then it's going to be several weeks for manufacturing before CAR T-cell therapy becomes available. This is a myeloma patient who has a lot of disease burden. These would be patients for whom we would have to think about: do I have an effective bridging therapy available? With the expanding treatment landscape of multiple myeloma, we have more choices available, where, in reality, all of my patients will have some bridging option available if I were to direct all of them in the direction of CAR T-cell therapy.

Bispecific antibody therapies come with their own advantages. We don't need any bridging therapy. They are off the shelf. They are ready the moment we have a patient consent and insurance authorization to move forward with them. These are more quickly available in our clinic and can be started at short notice, and that's one of the big advantages that come with it. At the same time, with more awareness around bispecific antibodies, the majority of the oncology practices that we collaborate with are able to do this locally once the initial ramp-up is done.

From a patient perspective, when it comes to CAR T-cell therapy, where they will be coming initially for apheresis and then afterward for lymphodepletion, CAR T infusion, and a few weeks of monitoring, the duration of time somebody would need to be in an academic center for bispecific therapy initiation is much shorter. We generally ask our patients to be there for 6 to 7 days, get this treatment going, and make sure that they are tolerating the initial period of this bispecific initiation, and then these patients are transferred quickly back over to their local oncologist.

I think beyond considering all the logistical elements that come into play, thinking about what CAR T-cell therapy and bispecific therapy are, what really also changed is that we are getting more and more data on how these therapies could compare to each other. We don't have a trial comparing one against the other, but if one were to look at trials across the board, CAR T-cell therapy and bispecific therapy, if you look at long-term efficacy, those results are very similar between cilta-cel [ciltacabtagene autoleucel; Carvykti; Johnson&Johnson/Legend Biotech], comparing that to daratumumab and a teclistamab combination.

So, I think this is becoming a real question: we have therapies that are inherently different but at the same time have comparable efficacies. They have a different toxicity profile, and they have different asks. It's a more nuanced discussion that's becoming more common in our clinics.

AJMC: What does the referral pathway look like when a rural community oncologist identifies a CAR T– or bispecific-eligible relapse? Where does it usually stall?

Godara: From a program standpoint, our goal is that the moment we get these referrals, especially if it is for CAR T-cell therapy or bispecific therapy initiation, we assume from the get-go that these patients are probably in need of these therapies yesterday. We work with that hypothesis in getting these patients into our clinic as quickly as possible. Ideally, we would like to see these patients at the time when they are maybe starting to show that biochemical progression, or these are patients where they have just started a new line of therapy, and we know the response from this new line of therapy is going to be a brief, definite duration, and they are going to need one of the immunotherapies as a later line, of course.

Having plugged in with that patient to talk about the next line of therapies, to talk about efficacy and toxicities, and based on a patient preference, what would be their preference for the next line of therapy? There are many such considerations that we would like to have that conversation as early as possible in the clinic.

When it comes to what slows this process down, a lot of times it's about whether this therapy needs to be done immediately vs it being more of a future consideration. That's thing number 1. Thing number 2 is that 1 thing that we realized quite early in this process is that if we were to ask every single patient to come down here 6 hours, 8 hours, away to Salt Lake City and see us in the clinic and then talk about these therapies, we are going to lose important time. It might be somewhat of a barrier in access to these patients when they're not able to travel that far of a distance.

The one way we overcame that limitation was to have licenses, medical licenses, in the neighboring states. Many times, these conversations are not happening in person in the clinic; they are happening virtually. That helps overcome the access situation, where patients can quickly get into a conversation about these treatments with us virtually through our clinics. Once they have all the information, once we provide them all the logistical elements that would be needed for this therapy, patients make a decision. They get back to us, and we decide what the next course of action will be.

But there are certainly situations where someone doesn't have a caregiver available, and that happens quite a lot; people are working, and their caregivers are busy with their own lives. For both CAR T-cell therapy and bispecific therapy, we do have requirements for having a caregiver available, at least for the initial period of the therapy. Sometimes that can stall the pathway to these CAR T-cell therapies or bispecific antibodies. Sometimes, insurance equations come into play as well when it comes to CAR T vs bispecific decision-making. Some insurance companies may prefer a bispecific antibody to be used at the time of first relapse vs using CAR T-cell therapy. A lot of these extra diseases, extra patient elements can sometimes slow down this process.

AJMC: How do you approach treatment and toxicity management for patients who may be older, frailer, or have more comorbidities than those enrolled in clinical trials?

Godara: I think this is one of the things we have become better at in the last few years with all the hands-on experience we have had with CAR T-cell therapy and bispecific antibody therapy, that we can really individualize these treatment decisions rather than following some type of algorithm in deciding the next line of therapy. Knowing our patients, knowing their disease, can really help us choose the right next treatment for these patients.

For patients who are older in my clinic or who have a lot of comorbidities or any of the major health issues that make me worried about their tolerance for CAR T-cell therapy or tolerance for any toxicities that may happen after CAR T-cell therapy, my preference is to discuss bispecific antibodies with them. With bispecific antibodies, too, we had, initially, a very high rate of cytokine release syndrome when these therapies were initiated. But with the ramp-up being instituted and with the availability of prophylactic use of tocilizumab, there's a lot of toxicity mitigation we can plan for and choose to do when we are starting these types of therapies.

When we talk to our patients about, for example, starting bispecific antibodies, we talk to them about “These are the toxicities. What are the ways we are going to mitigate them?" Then, we also talk about, "What will the plan look like when they return home?" We want our patients to be on prophylaxis against shingles and prophylaxis against pneumonia. We want them to be prophylaxed again. We want them to get prophylaxis against infections through monthly intravenous immunoglobulin.

Our dream protocol is that we make this discussion; we start the patient on these new therapies, and then we share what their monitoring as well as prophylaxis regimen should look like when they return home. We hope that the results that we see in our own patients who are treated fully at our institution can be replicated even for a patient who lives in Idaho or who lives in Montana so that we can provide the same level of care across the board.