With New Bispecific Antibodies in Multiple Myeloma, Nurses Need To Know How to Manage CRS

Elizabeth Aronson, MSN, FNP-BCN, OCN

It is exciting that there are more targetable proteins in multiple myeloma, according to Elizabeth Aronson, MSN, FNP-BCN, OCN.

“In years past, I think myeloma [specialists] sometimes were jealous of other malignancies, because they had a lot of great different protein targets for therapies,” she said. “Now everyone else is going to be jealous of us because not only do we have BCMA—we have GPRC5D, and soon [we may have] FCRH5. It is just exciting.”

Specifically, in August 2023, the FDA approved 2 novel bispecific antibodies to treat patients with relapsed or refractory disease.

On August 10th, 2023, the FDA granted accelerated approval to talquetamab-tgvs (Talvey), a bispecific antibody therapy, to treat patients with relapsed or refractory multiple myeloma who have already received at least 4 lines of treatment, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. On August 14th, 2023, the FDA granted accelerated approval to elranatamab-bcmm (Elrexfio) to treat adults with relapsed or refractory multiple myeloma who have already undergone 4 prior lines of treatment, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

In an interview with Oncology Nursing News®, Aronson, who is a clinical nurse practitioner specializing in bone marrow transplant and immune effector cell therapies at Mount Sinai Hospital, spoke to the significance of these approvals. She offered her opinion on the supporting data and her perspective on what best nursing practices are going to look like with these new agents.

Oncology Nursing News: What stands out to you about the MagnetisMM-3 trial?

Aronson: For elranatamab, the pivotal clinical trial that led to FDA approval is the MagnetisMM-3 trial (NCT04649359). This particular target, B cell maturation antigen [BCMA], is very popular. We have 2 CAR T-cell therapy products that are approved, we have teclistamab, another bispecific antibody that has been approved that has the same target. It has a similar route of administration. All the bispecifics that are currently approved are administered subcutaneously—teclistamab (Tecvayli), talquetamab—are all given subcutaneously with some little differences in the dosing schedule—either weekly or every two weeks.

What stands out about the MagnetisMM-3 trial is that this population was even more heavily pretreated; over 90% of patients were in the triple-class refractory [setting]. So that means they had [received] our standard-of-care drugs, and their myeloma continued to progress. What is particularly notable is that many studies with treatments that target BCMA do not allow patients who had already been exposed to BCMA-directed therapies to participate in the trial, but the MagnetisMM-3 trial did.

As we get more and more therapies on the market, the question coming up a lot is, do BCMA –[directed] therapies work on somebody who has received them before? How do we sequence them? This data is particularly relevant the more BCMA therapies we have.

The overall response rate (ORR) was around 64%, that is the percentage of patients who had some degree of response and that was comparable to other bispecific antibodies that have been approved targeting BCMA.

When you have 2 drugs that are kind of falling into similar categories, you are going to look at risk profile. The risks of bispecific antibodies are similar to CAR T-cell therapies insofar as those immune effector cell toxicities. The things that we usually focus on are cytokine release syndrome (CRS), and neurotoxicity. The rate of CRS was around 67%, so 67% of patients had some degree of cytokine release syndrome, which is comparable to the other bispecific antibodies in the market right now, and most of these were grades 1 or 2. [This is] very manageable. We are looking at acetaminophen and tocilizumab (Actemra) supportive care. These patients were not going to the intensive care unit (ICU) or having severe CRS.

The other thing that's notable when we are comparing products, particularly for BCMA-directed therapies, is that the risk of infection is very high. Especially with teclistamab, [where] it seems like that risk of infection is not only significant, but it seems to go up over time.

Elranatamab is a new medication, but it seems to have a lower overall rate of severe infections. That might be something to consider.

Can you unpack the data behind the MonumenTAL-1 study (NCT04634552)?

Our center participated in the MonumenTAL trial, and we enrolled the highest number of patients, which we are proud of.

We are all really excited about talquetamab. Talquetamab is the first therapy approved that targets GPRC5D. In some ways, it is very similar to the other bispecifics that we talked about. It is given subcutaneously, we use a step-up dose schedule to mitigate CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), we use premedications to mitigate those toxicities, and the response rates are similar.

The overall response rate in monumenTAL—they broke it down into patients who received either biweekly or weekly dosing—but approximately 70% of patients had a degree of response, regardless of which cohort they were in. Again, just like with elranatamab, this was a heavily pretreated population. Approximately three quarters of the patients were triple-class refractory, and [had a] similar median numbers of lines of therapy. Unlike the teclistamab study, they allowed patients with prior BCMA-directed therapies, which makes sense, [since with talquetamab] we are using a different target.

It was given either weekly or biweekly subcutaneously. Approximately three quarters of patients had cytokine release syndrome, but anything more than a grade 2 was rare.

What makes talquetamab unique is the toxicities—which are unique to the GPRC5D—being expressed in keratinized tissues, so fingernails, the surfaces of the palms and soles. All of the bispecifics have some incidence of injection site reactions, but with talquetamab, dermatologic toxicities look a little bit different. Patients sometimes require steroid creams or even small doses of oral steroids.

Aside from the dermatologic toxicities, the taste changes were significant. We are still figuring out how those taste changes evolve if they persist for the duration of treatment. For the majority of patients, when they stopped treatment, their taste returned to normal, but as we treat more patients, especially in the real-world setting, I think we will get a lot more information about how to manage those toxicities and how they evolve over time.

For those who do not work in clinical research but are interested in the latest evidence-based practice, how would you interpret the data?

With multiple myeloma, the first question you should ask yourself is what the patient population looks like. For bispecific and novel therapies, typically, we are looking at a relapsed and refractory population, so patients that have been exposed to all the drugs we have currently available and their disease has continued to progress. Looking at the patient population, and how many lines of therapy they have had gives you an idea of how valuable these treatments are, because a relapsed/refractory population typically [includes] patients who would have a very poor prognosis and limited expected survival.

Then, of course, we get excited about the ORR. That number tells you what percentage of those patients had any response. It will further be driven down into patients who had a complete response, or a partial response, and things like that, but the high point is that ORR. Then, of course, we are always interested in the route of administration and the dosing schedule, because that impacts patient quality of life. Finally, I would say the safety profile: what are the risks involved?

Both bispecific antibodies have been granted accelerated approval for patients with relapsed or refractory disease. How do you anticipate that they may be incorporated into the treatment fold?

What stands out is the infectious risk. Talquetamab does not seem to have this risk of severe infections and it is significant with teclistamab. Although it is a lot less with elranatamab, it is still significant. Patients often die from infections before they die from multiple myeloma so that is something that will contribute to people's decision making.

When these [treatments] move into the community setting, people may need to pick and choose which BCMA-directed therapy [is appropriate for them], and talquetamab is standing out in its own category.

Right now, especially working in the cellular therapy setting with CAR T-cell therapy, a lot of times, patients are progressing before or sometimes progressing in between collection and administration of their CAR-T cells. There are questions about T cell exhaustion and other factors when we are using multiple immune effector cell treatments. But talquetamab, having a different target, may be really a valuable tool to bridge patients to CAR T. We do not know the answer to [whether] that will be an effective strategy, but I think there is a real potential there.

When integrating these agents into clinical use, what do you think will be important to keep in mind from a logistical standpoint?

It is so important that we have good upfront treatment strategies and triage strategies, and nurses and nurse practitioners are crucial to that. What is exciting about this is that [with] some of these more unique side effects, like CRS and ICANS, we have gotten a lot better at management. A real opportunity lies in developing good frameworks for managing these toxicities in outpatient settings, implementing pathways in emergency settings, and implementing triage by nurse navigators and nursing staff in the clinic setting.

What we have seen is that toxicities with bispecifics are significantly lower grade. It is rare that patients need an ICU admission. [However,] expertise in managing those toxicities is necessary because we are having so many approvals with drugs that have a similar adverse event profile. This is kind of the new neutropenia, or the new chemotherapy-induced nausea and vomiting. Oncology nurses are going to need to have this in their tool belt: a toolkit for understanding CRS and triaging it and managing it. What I have seen since I have been working with CAR T, since 2017, is that the better we manage CRS and ICANS, the better patients do.