BCMA-Directed Bispecific Antibodies Navigating a New Era in Relapsed/Refractory Multiple Myeloma

The treatment landscape for multiple myeloma has undergone a rapid evolution, shifting from traditional therapies to highly targeted immunotherapies that have significantly improved patient outcomes. At the 67th American Society of Hematology Annual Meeting and Exposition, a panel of experts convened for an Around the Practice^® discussion, hosted by CancerNetwork, to explore the practical integration of BCMA-directed bispecific antibodies into clinical care.

Moderated by Sundar Jagannath, MBBS, professor of medicine at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Tisch Cancer Center, the panel featured: Ajay K. Nooka, MD, MPH, FACP, associate director of clinical research for Winship Cancer Institute of Emory University; Mohan Krishnamachary, MD, hematologist/oncologist from Suburban Hematology-Oncology Associates; Nisha Joseph, MD, associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine; and Donna Catamero, MSN, ANP-BC, OCN, CBCN, from Mount Sinai.

With the recent approval of linvoseltamab-gcpt (Lynozyfic) in July 2025,¹ clinicians now have 3 FDA-approved BCMA-directed bispecific antibodies at their disposal: teclistamab-cqyv (Tecvayli), elranatamab-bcmm (Elrexfio), and linvoseltamab. These “off-the-shelf” T-cell engagers have revolutionized the treatment of patients with triple-class refractory disease—those who have typically had 4 to 5 prior lines of therapy—by doubling historical response rates from 30% to between 60% and 70%.

Jagannath / We now have 3 FDA-approved BCMA-directed bispecific antibodies: linvoseltamab, teclistamab, and elranatamab. The addition of linvoseltamab has broadened our treatment landscape. We are gaining experience in the real world with these bispecific antibodies, and therefore, this conversation will be very timely for our clinicians. Let’s start with how these agents are being used in everyday practice. Just to get a high-level overview, what is the great excitement about the bispecific antibody, or T-cell engager, or T-cell redirection therapy—all these terminologies are used. What is the great excitement about these bispecific antibodies?

Nooka / You look at the treatment evolution of multiple myeloma therapies, Dr Jagannath: What we saw was a landmark response rate of around 30% for those patients with late relapsed myeloma. What the bispecifics brought to us is doubling those response rates all the way up to the 60% to 70% mark in those patients [who] are triple-class refractory, [who] have seen 4 to 5 prior lines of therapy, and that’s a big deal. That has changed the entire landscape of how we treat multiple myeloma, and now we are seeing these agents [being] so safely administered, and those could be given safely in combinations as well. There [are] early data coming in. This is paving a path for a completely new revolution in how to use these immunotherapies for bettering the outcomes of patients with multiple myeloma.

Jagannath / BCMA is an important target, and BCMA is used as a target, not only for bispecific or trispecific antibodies, but also for CAR [chimeric antigen receptor] T-cell therapy. How do bispecific antibodies differ from CAR T-cell therapy?

Joseph / One of the benefits of bispecific antibodies, potentially compared with CAR T-cell therapy, is that these are off-the-shelf products, so these don’t need to be manufactured. They’re ready to go. If you want the patient to start a bispecific, you can get them going in the next week. In contrast to that, what CAR T-cell therapy is [doing] instead of an off-the-shelf product, what we’re doing there is we’re still using and engaging T cells, but we’re using the patient’s own T cells that we take out. We then engineer them to express this receptor that then targets whatever we are targeting. In this case, the 2 FDA-approved CAR T-cell therapies we have target BCMA. That manufacturing process takes anywhere from 2 to 4 weeks, depending on the product, whether you’re using commercial [products] or something in trial; then you are infusing that product back into the patient. That’s much more of a process than how we would prescribe and then administer a bispecific antibody. There are similar and then different [adverse] effects, obviously, between the 2 products because of how they’re constructed and how we deliver them.

Jagannath / Ajay, could you just cover what [the differences are] between [the bispecifics] in terms of response rate, the frequency of administration, or the toxicity? When we come to the bedside, how and when to use these drugs, we can go in detail, but at least give us just the overall idea about the response rate and what is known about these 3 different drugs.

Nooka / The teclistamab, which was the first approved [of these 3 drugs], was based on the phase 2 MajesTEC-1 trial [NCT04557098]², and this led to a response rate of close to 61%. So what you’ve seen across the board—whether it is elranatamab approved based on the phase 2 MagnetisMM-3 trial [NCT04649359]³ or the linvoseltamab approved on the phase 1/2 LINKER-MM1 trial [NCT03761108]⁴—all these have resulted in response rates of 60% to 70% and the highest response rate, as we see, was with linvoseltamab, which is the most recently approved one, in July [2025].

What are the toxicities that come with each of these antibodies? There are 3 main things that one can talk about, [which are] the immediate toxicities of cytokine release syndrome [CRS]: the neurotoxicity and the cytopenia and the infections. I would combine the cytopenia and infections, and we can have a good discussion about what the differentiating factors between all 3 of them are, but the cytokine release syndrome, if you look at each of these 3 agents.

Teclistamab was the one that was first approved. It had higher [toxicity] rates, almost 55% to 60% CRS rates, but the majority of these are grade 1 toxicities. The CRS happens in around 15% of the patients. Now, if you look at the elranatamab, the numbers are decreased. We look at the LINKER-MM1 trial with linvoseltamab, and the numbers are quite decreased. The CRS rates are in the range of around 40%; if you start to look at the infection profile, the same numbers exist. Unfortunately, some of those earlier trials were done at the time of COVID-19, at the time when there was a huge pandemic going on; there was a lot of toxicity with COVID-19…. Grade 3 infections occurred in close to 55% of patients who received teclistamab in the MajesTEC-1 trial. That number has come down when we start to look at the elranatamab range of around 40% with the LINKER-MM1 trial with linvoseltamab; that number has further decreased.

There are several factors that happen simultaneously. We started to look for it proactively, and started to have consensus on how to safely administer these agents, and started to give these patients prophylactic IVIG [intravenous immunoglobulin] and make sure that the patients have decreased risk of infections. We have been proactively doing this over time. What you see is the [result]: There is the new antibody that was recently approved, linvoseltamab, having the least infection risk [and] high-grade infection risks. Similarly, the cytopenias also pan out during the same time.

Jagannath / Donna, what is needed in terms of preparing the team [to give a] bispecific antibody?

Catamero / There’s a lot of coordination of care and transition of care. Is this patient coming from the community to an academic center, where I’m going to have to transition the patient back to the community? I want to make sure I have that communication with the referring center but also educate the patient on CRS. We haven’t even talked about prophylactic tocilizumab, which makes it even easier to give; it affords us the opportunity to give these drugs as outpatient, so we talk about the main [adverse] effects. CRS should be expected. However, if we’re giving prophylactic tocilizumab that significantly decreases and then gives us that opportunity to give this as an outpatient. Neurotoxicity is less common with bispecifics, but we do want to make sure that there is a care partner involved, so that if the patient is getting outpatient dosing, someone is monitoring the patient. The most important thing we need to educate patients on is infection. As providers, we’re good at managing CRS, even neurotoxicity. They’re self-limiting. We have steroids and tocilizumab to manage CRS, but infections can be tricky, and so [we mitigate] this with IVIG, monthly prophylaxis, making sure our patients are up to date on their seasonal vaccines, and educating patients when to inform their providers. There’s a big component of transition of care. If I’m returning someone to the community, [I am] making sure that I’m communicating what the follow-up plan is and how we proceed with care for that patient.

Jagannath / When you are taking care of a patient, what do you do in terms of vaccinations and use of IVIG, etc, in your practice?

Krishnamachary / The one thing [that] perhaps was done, which is missing, is stem cell transplantation. It did not feature in this, but we have a vaccination schedule that we use post transplant, 6 to 9 months post transplant, which is standard, and we implement that. Apart from the seasonal vaccine, we follow the regular CDC guidelines. In terms of the infection prophylaxis, most of them are on antivirals, and antivirals are given indefinitely. Once the diagnosis is made, and once we start their treatment, it’s on indefinitely, and PJP [Pneumocystis jirovecii pneumonia] prophylaxis also [is given] during the initial induction phase, we keep it on, and in the maintenance phase, we drop it. This is a patient where we would put them back on PJP prophylaxis, and the monthly IVIG, and a good number of patients, even prior to this, would have already received IVIG simply because of the increased risk of infections.

Joseph / If I could just make a point about IVIG quickly, it is in contrast to how we use IVIG in other contexts. In multiple myeloma, where you might be waiting for that IgG level to drop or be driven by recurrent infections in a season, we recommend and use IVIG monthly, regardless of IgG level, while the patient is on a bispecific antibody. Even if you discontinue that bispecific antibody, you would want to think about continuing that potentially for a few months before you because you don’t see the constitution right away. That’s an important piece, instead of waiting for something to happen, being proactive and making sure that patients are getting monthly IVIG while they’re on bispecific therapy, and that continues. In contrast to CAR T-cell therapy, where that immunocompromised state is a little bit more self-limited, this would be something that we’d have to continue as long as patients are on bispecifics, and that has been one of the reasons we’ve seen other reasons, schedule and other things, but that we’ve seen a decrease in the clinical setting of the infections that we see as compared with some of the early trials.

Jagannath / I would like to have a dialogue between Donna and Dr Krishnamachary [about] when it’s a matter of transitioning patients from academic center to the community center. What is it you are educating? What is it he would like to know from when the patient gets transitioned from, say, Emory University to him after a step-up dosing? What is it you think about?

Catamero / There’s logistics, and there’s patient management. First, with the logistics, the patient comes to my academic center. If we’re doing an inpatient dosing, I want to make sure there’s insurance that comes into this, too. If a patient switches from my institution to your institution, that’s 2 different insurance approvals, and you don’t want to delay the next dose when they go back to their community provider. You need to make sure that’s in the works. We can time things out, so I know when I’m going to finish my step-up dosing. You make sure that the next appointment is already scheduled at the community center, and then that communication handoff, which I think often lacks between the academic center and the community. How did the patient tolerate the step-up dosing? Were there any concerns? How to manage the patient, moving forward with the IVIG, the infection risk, making sure that those appointments are understood in the community, what is needed for that community handoff? Because we were so reliant on our electronic medical records, that documentation, making sure all the key components of what is needed for patient care [would] be communicated to the sites.

Krishnamachary / I practice in a location where we are very lucky, we have a very good tertiary care hospital, and we know the doctors personally, and we rely not just on the electronic medical records, but also, we call and we speak. By the time I’m already sending them to a tertiary center to get the step-up dose of bispecifics, I know the patient very well. I have a good understanding of their social history and so on. I have a good understanding of their medical history. What I’m relying on at the tertiary care center is, when are you giving the drugs? I would need the dates of when they’re [being administered], how much they’re getting, and how they were able to tolerate [them], and that direct communication between the 2 teams is very critical. I’m thinking of this as a pilot program where I involve my supervisor, our clinic managers, and our pharmacy directors to communicate directly with the tertiary care center. We have a lot of back-and-forth communication that way. One of my patients is going to start one of the bispecifics, and we are already prepared for the third dose.

Catamero / That appointment should be booked before that patient gets discharged. It’s that…nurse-to-nurse communication to make sure that the patient is set up and making sure the insurance [is taken care of]. Because it’s a different approval from one institution to the next, that can delay a patient from getting their next dose.

References

1. FDA grants accelerated approval to linvoseltamab-gcpt for relapsed or refractory multiple myeloma. FDA. July 2, 2025. Accessed February 12, 2026. https://tinyurl.com/3ubmzw83
2. Garfall AL, Nooka AK, van de Donk NWCJ, et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42(suppl 16):7540. doi:10.1200/JCO.2024.42.16_suppl.7540
3. Prince HM, Bahlis NJ, Rodríguez-Otero P, et al. MagnetisMM-3: long-term update and efficacy and safety of less frequent dosing of elranatamab in patients with relapsed or refractory multiple myeloma. Blood. 2024;144(suppl 1):4738. doi:10.1182/blood-2024-208192
4. Bumma N, Richter J, Jagannath S, et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42(22):2702-2712. doi:10.1200/JCO.24.01008