How Have Bispecific Antibodies Evolved in Multiple Myeloma?

In a conversation with CancerNetwork^®, Hans Lee, MD, director of multiple myeloma research at Sarah Cannon Research Institute in Nashville, Tennessee, spoke about the evolving role of bispecific antibodies targeting BCMA and GPRC5D in multiple myeloma. He described how these agents were initially approved in late-line disease for patients with at least 4 prior lines of therapy who were triple-class exposed to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Since then, randomized phase 3 trials have shown progression-free survival and overall survival benefits with bispecific antibodies compared with standard therapy in earlier relapse. Of note, the FDA approved teclistamab-cqyv (Tecvayli) in combination with daratumumab (Darzalex) after at least 1 prior line of therapy in March 2026.¹

Lee discussed common misconceptions about bispecific antibodies, how he weighs them against CAR T-cell therapy, what community practices need to safely deliver them, and where he sees the field heading. On top of efficacy, he framed broader community access as the defining challenge for bispecific antibodies in multiple myeloma over the next several years as these agents move into earlier lines of therapy.

CancerNetwork: Bispecific antibodies have moved quickly from late-line, heavily pretreated indications to being studied and even approved earlier in the treatment course. How would you characterize the current stage of that evolution across the field right now?

Lee: There [was] certainly a lot of excitement when bispecific antibodies targeting BCMA and GPRC5D were approved in late-line myeloma. Initial approvals were in patients with at least 4 prior lines of therapy, triple-class exposed to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. In the last year or so, we have seen multiple trial readouts looking at bispecific antibodies in randomized phase 3 studies, demonstrating that bispecific antibodies targeting BCMA and GPRC5D not only improve progression-free survival but also overall survival compared with standard conventional therapies in patients with early relapsed/refractory multiple myeloma. There are a number of pending phase 3 trial readouts in this space that we expect to be positive as well.

We are seeing a shift of bispecific antibodies into earlier-line myeloma. Now, we have teclistamab plus daratumumab approved [after] at least 1 prior line of therapy,¹ and we would expect more to come soon thereafter. In newly diagnosed myeloma, there are also many clinical trials evaluating bispecific antibodies, both as part of induction therapy and as part of consolidation; these trials are very promising and very exciting. It will only be a matter of time before we incorporate these agents in newly diagnosed patients as well.

What is the biggest misconception you still encounter, whether from patients or referring physicians, about what a bispecific antibody is and how it compares to other options?

Mainly, it is the monitoring of potential early toxicities including cytokine release syndrome [CRS] and, rarely, immune effector cell-associated neurotoxicity syndrome [ICANS], and of course late infection monitoring as well. In terms of the biggest misconception, I think it is that these agents can only be given at large academic centers rather than where patients are being treated locally; I really want to emphasize this. Because they are off-the-shelf, bispecific antibodies do not require a complex facility to manufacture and store cells the way CAR T-cell therapy does. Patients can get a highly effective T-cell–redirecting therapy in their local practice setting, and I really want to stress that this can indeed be given in the community oncology setting with outpatient step-up dosing and the appropriate organizational structure.

Beyond avoiding manufacturing wait times, what does an off-the-shelf therapeutic option actually mean for a patient’s day-to-day experience and treatment decision-making?

Off-the-shelf treatment options are basically drugs that are available immediately to patients in need of therapy, relevant to their disease status. Historically, all conventional oncology drugs have typically been off-the-shelf; you have a drug shipped to the treating facility, and it can be administered right away. What makes bispecific antibodies unique is that they are part of a new class of drugs from the last 5 to 7 years called T-cell–redirecting therapy, which largely encompasses bispecific antibodies and CAR T-cell therapies. There are off-the-shelf formats for CAR T-cell therapy currently being investigated, such as allogeneic CAR T-cell therapies and even in vivo CAR T-cell therapy, but in the current state, bispecific antibodies represent the major option for off-the-shelf T-cell–redirecting antibody therapy. This enables patients to have much better access to these highly effective therapies.

In the context of multiple myeloma, we have never seen response rates as high as we do with bispecific antibodies and CAR T-cell therapies. It’s also not just the response rates; it is the depth of response and the duration of response. These have been unprecedented. The challenge has been access; at the present moment, the majority of patients who are candidates for these therapies still do not have access to T-cell–redirecting therapies in their local treatment setting, although bispecific antibodies do present an opportunity for patients to have access because they are off the shelf and can be delivered, particularly in community oncology settings, in the local treatment setting.

How do you weigh the trade-off between a bispecific antibody’s more chronic, ongoing treatment burden vs CAR T-cell therapy’s single-infusion, front-loaded intensity?

This is a conversation I have with patients every day. The thought is that patients should get some form of BCMA T-cell–redirecting therapy as early as possible in the relapsed/refractory setting, either a BCMA bispecific antibody or BCMA CAR T-cell therapy, whichever is available to the patient. There are trade-offs: a single infusion of CAR T-cell therapy [requires] a lot more upfront activation energy to get a patient to CAR T, including apheresis, manufacturing, infusion, and monitoring, especially in the short term after infusion. I would also say that while CAR T-cell therapy is considered one-and-done, there is still a lot of supportive care needed afterward. It is important to be realistic with patients in that discussion, including infection monitoring, intravenous immunoglobulin [IVIG] after CAR T-cell therapy, cytopenias that can occur, and other issues. It is important to recognize that there are still additional steps involved in the post-CAR T setting that are mainly supportive care.

With bispecific antibodies, since they are off-the-shelf, they can be administered right away, so the activation energy to get a patient started is much less than with CAR T-cell therapy. There still needs to be a plan and a process in the local practice setting for monitoring early potential adverse events [AEs], mainly CRS and, rarely, ICANS. The incidence and severity of CRS is lower with bispecific antibodies compared with CAR T-cell therapy. That’s one nice thing. We are also learning a lot more about how to mitigate these early AEs, such as giving prophylactic tocilizumab [Actemra] prior to the first step-up dose, which has decreased the incidence of CRS from 50% to 70% down to less than 10% to 15%, enabling outpatient step-up dosing.

In the long term, infection monitoring is critical with bispecific antibodies, and giving monthly IVIG is important. We are also learning that treatment until progression is probably not the path forward; we are looking at fixed-duration treatment approaches, giving perhaps a year or 2 of bispecific antibody-based therapy. [Because] these therapies can elicit deep and durable responses quickly, it is probably not necessary for patients to stay on therapy forever, as has been the historical paradigm in myeloma.

Given that CRS and ICANS risks are concentrated in an early step-up dosing window, what must be true about a community practice’s infrastructure and staff training before it’s ready to take that on safely?

Before a practice decides to incorporate bispecific antibodies into their treatment, it is important to assemble the key stakeholders in the practice to have a plan and a strategy for how to administer these drugs. That includes the physicians, advanced practice providers, pharmacists, nursing staff, particularly infusion nurses and triage nurses, and social workers and other ancillary staff. It is important to map out, step by step, what the process would be for a patient to get on a bispecific antibody, from getting insurance approval, to selecting inpatient vs outpatient step-up dosing, to how patients are monitored afterward in the initial step-up dosing period for CRS and ICANS.

I will emphasize that the majority of CRS with bispecific antibodies is grade 1, which is essentially a fever, and oncologists are very comfortable managing fever. It is important to recognize and be aware of the different severities CRS could evolve into, but by and large, most CRS is grade 1, particularly with mitigation strategies like prophylactic tocilizumab. These are AEs that can certainly be managed, even at smaller oncology practices; it is mainly about developing a plan of action upfront to implement the administration of these drugs.

How do you decide when a patient is ready to transition from an academic center to a community practice for ongoing bispecific administration? What would make you hold off?

If there is one take-home point I would want to make, it is that bispecific antibodies can be administered in the community practice setting. At the same time, I also recognize that it may still be difficult to do step-up dosing at certain practices, so there are hybrid models where step-up dosing is done at a larger community center or an academic center, and the patient then transitions back to the community center for maintenance dosing after cycle 1. The rationale is that the risk for early AEs such as CRS is typically limited to the step-up dosing period within the first couple of weeks. CRS and ICANS are exceedingly rare after cycle 1, so that is an appropriate time for patients to transition back to their local oncologist if step-up dosing is done elsewhere.

I do not see a reason why that transition could not happen. The only exception is that, with BCMA bispecific antibodies in particular, giving IVIG supportive care is critical. If there is some reason a patient could not get IVIG at their local practice setting, which would be unlikely, that might be a reason to stay at the larger tertiary center. But by and large, patients should at minimum be able to transition back to their local oncology practice after cycle 1. I would also encourage practices to explore giving step-up dosing in their local treatment setting because even needing to get step-up dosing at the academic center is itself a barrier to access, as some patients may not be able to travel to a larger tertiary center. We need to find ways for patients to have access to these agents where they live and are treated.

Looking ahead, do you think the field is moving toward bispecifics becoming a primarily community-delivered therapy, with academic centers reserved for CAR-T and clinical trials, or will the picture stay more mixed?

I think we are still in the very early days of bispecific antibodies in oncology, and specifically in multiple myeloma. My hope and anticipation is that, perhaps in 3 to 5 years, we will look back and say we were figuring out the optimal delivery mechanisms for these therapies. But with additional mitigation strategies, such as prophylactic tocilizumab prior to the first step-up dose, I do feel these will be a major component of treatment given in the community oncology setting. I think this will enable access for patients to a highly effective T-cell–redirecting therapy.

Especially as these agents in multiple myeloma move into earlier lines of therapy, including newly diagnosed myeloma, it will be imperative for oncology practices, particularly community oncology practices, to incorporate these agents into their repertoire of treatment options to offer patients because these will be the standard. These will form the standard backbone agents for multiple myeloma therapies for the foreseeable future.

Reference

FDA grants third approval under the National Priority Voucher Program. News release. FDA. March 5, 2026. Accessed August 19, 2026. https://tinyurl.com/45hhbpau