What Does the Future Hold for Bispecific Antibodies in Multiple Myeloma?

As part of a visit to Columbia University Irving Cancer Research Center, CancerNetwork^® sat down with Rajshekhar Chakraborty, MD, to learn about developments and potential future initiatives for the use of bispecific antibodies and other cellular therapies for patients with multiple myeloma and other plasma cell disorders. Chakraborty discussed strategies for adopting novel treatment strategies more prominently across community practices and reviewed key clinical trial data that may impact the paradigm.

According to Chakraborty, an assistant professor of medicine in the Division of Hematology/Oncology at Columbia University Irving Medical Center, improving access to bispecific antibodies in the community setting may come down to factors including physician education, Risk Evaluation and Mitigation Strategies (REMS) certification, and long-term management of potential toxicities. Additionally, he broke down “remarkable” results from studies like the phase 3 MajesTEC-3 trial (NCT05083169), which led to the FDA approving teclistamab-cqyv (Tecvayli) plus daratumumab hyaluronidase-fihj (Darzalex Faspro) for patients with relapsed/refractory multiple myeloma.¹

CancerNetwork: What are bispecific antibodies stand out to you, especially in the management of multiple myeloma and other plasma cell disorders?

Chakraborty: Bispecific antibodies have been a great asset in the treatment armamentarium of multiple myeloma and other plasma cell disorders. When we think about bispecific antibodies, we usually think about them as different targets. For example, we have the BCMA bispecific antibodies. We have the GPRC5D bispecific antibodies. Then, there are some other targets that are still in the pipeline. For example, FcRH5. The 2 targets that are already FDA-approved [include] BCMA bispecific antibodies, among which there are 3: teclistamab, elranatamab-bcmm [Elrexfio], and linvoseltamab-gcpt [Lynozyfic]. Of GPRC5D bispecific antibodies, talquetamab-tgvs [Talvey] is the only one that's currently FDA-approved. We are using them a lot in our treatment for relapsed/refractory multiple myeloma and in other plasma cell disorders like AL amyloidosis and monoclonal gammopathy of renal significance [MGRS].

What can be done to improve the adoption of bispecific antibodies in the community setting? What barriers or obstacles need to be addressed to improve access to treatment in this setting?

This is a great unmet need because so many of our patients are on bispecific antibodies and patients don’t like to drive to an academic medical center. They want these therapies close to home. [Usually], I see [the barriers] as 2 or 3 different buckets. One is education about bispecific antibodies in the community; that’s still an unmet need. They are now available in earlier lines of treatment. For example, the teclistamab and daratumumab combination [is] FDA approved for patients with 1 prior line of therapy.¹ Similarly, single-agent teclistamab [may also be approved]. Now, they will be in earlier lines of therapy. There needs to be increased education among community oncologists that bispecifics can be given earlier.

The second barrier I see is having community oncologists universally REMS certified for all these bispecific antibodies, given there is still a fear factor for cytokine release syndrome [CRS] and immune effector cell–associated neurotoxicity syndrome [ICANS]. That’s from the CAR-T literature. But now we know that [for] patients who get bispecific antibodies in clinical trials, several large, randomized trials have been done and very few patients have developed clinically significant CRS. Most of the CRS is grade 1; grade 2 CRS is very low, and grade 3 and higher [CRS] is pretty much nonexistent. That education needs to happen in the community. CRS with bispecifics is very manageable. It’s rarely serious and almost never life-threatening.

The third thing I would say is the long-term management, with stringent infection prophylaxis, management of infections, and early assessment for signs or symptoms of infection. That’s where it’s usually less challenging to me because when patients are in long-term follow-up, they’re also sometimes being followed at an academic medical center once every 3 months or once every 6 months. We can guide that part of the care and can guide the community physicians as to what infection prophylaxis patients need to be on. But the first 2 parts—starting the education about the efficacy and the safety, getting all the community oncologists REMS certified, and removing the cloud from the fear factor regarding CRS and ICANS—are the main barriers.

How can clinicians optimize the management of adverse effects that may occur with the use of novel cellular therapies like bispecifics?

For bispecific antibodies, if we first focus on CRS, one of the things that we have learned is the use of prophylactic tocilizumab [Actemra]. Several studies have shown that the use of prophylactic tocilizumab decreases the risk of CRS. Now, we do not have any randomized data yet, but from the single-arm trials, it looks promising. For us, the more important part is that using prophylactic tocilizumab can enable the administration of these agents in the outpatient setting because we would even want to potentially prevent grade 1 CRS to avoid any unnecessary [emergency room] visits or patient anxiety. That’s number 1.

The second is, once patients get CRS or once patients have a fever, we typically give supportive care [with] early tocilizumab. It also helps in preventing the CRS from escalating into grade 2 or grade 3. These are predominantly for CRS.

But in my mind, again, the more important toxicity with bispecific antibodies is infection because that is something that we have to deal with over the long term, especially with continuous treatment. Several agencies—for example, the International Myeloma Working Group, the International Myeloma Society, and the CoMMit Consortium—have published guidelines on infection prophylaxis, and we just need to make sure that those are followed exactly with stringent infection prophylaxis. All patients must be on primary [intravenous immunoglobulin (IVIG)] prophylaxis, [Pneumocystis jirovecii pneumonia[ prophylaxis, and HSV prophylaxis. That needs to be followed for proper supportive care, and to prevent high-grade infections from happening in the first place.

How do you see findings from the MajesTEC-3 and MajesTEC-9 trials (NCT05572515) impacting multiple myeloma therapy in the long term?

MajesTEC-3 was just presented at ASH 2025, and there was a simultaneous publication in the New England Journal of Medicine.^2,3 It was one of the most remarkable results that we have seen in relapsed/refractory multiple myeloma thus far.

In the MajesTEC-3 trial, we saw a big difference in progression-free survival, as well as overall survival [OS] at a 3-year median follow-up. There were a couple of things that struck me and differentiated it from other regimens that we have in relapsed/refractory myeloma. First, for the progression-free survival [PFS] curve in the [teclistamab/daratumumab] arm, there is almost a plateau beyond the first 9 to 12 months. That is remarkable. We have not seen that kind of plateau even with randomized trials of CAR T-cell therapy in the experimental arm.

The second [thing] is at 3 years, we saw a PFS exceeding 80%; it was approximately 83% to 84% at 3 years with the teclistamab and daratumumab combination, which is, again, a remarkable result overall. One of the concerns that we all had was that [teclistamab/daratumumab] would have a high risk of infection and infection-related deaths. The results reassured us that, yes, there was a high risk of infection in the first 9 to 12 months, but once there was routine IVIG prophylaxis use towards the end of the trial, the infection risk did go down. Despite the infections and some unfortunate infection-related deaths, there was still an OS benefit. We think that as we translate these findings in the real world, we now know how to [perform] better prophylaxis for infection. We think that the risk of infection-related deaths will be much lower in the real world than what was in the trial.

Switching gears to MajesTEC-9, it was a slightly different trial that compared single-agent teclistamab to a control arm that could either be pomalidomide [Pomalyst], bortezomib [Velcade], and dexamethasone [PVd] or carfilzomib [Kyprolis] and dexamethasone [Kd]. A slightly different control arm here, and the patient population that MajesTEC-9 targeted was predominantly a daratumumab-refractory patient population, patients who had previously been exposed—and most of them were even refractory—to anti-CD38 monoclonal antibodies. This is a very high-risk patient population; in MajesTEC-3, almost none of the patients were daratumumab refractory.

[For] MajesTEC-9, we don't have the abstract or publication yet, but we did have a press release showing that there was a PFS and OS benefit with teclistamab over PVd or Kd.⁴ We are waiting for [more data at] upcoming meetings; they will hopefully be presented at ASCO or EHA. But the main area or niche where we are looking to position this is for patients who are relapsing on frontline daratumumab- and lenalidomide [Revlimid]-based regimens.

What other clinical trials in multiple myeloma or other plasma cell disorders do you anticipate having a big impact in the field?

Some of the clinical trials that are in the pipeline that we think have a potential to change the field in the upfront setting are the CARTITUDE-5 [NCT04923893] and CARTITUDE-6 trials [NCT05257083]. The CARTITUDE-5 trial is completely accrued, and it might read out any minute. It was a trial comparing CAR-T with ciltacabtagene autoleucel [cilta-cel; Carvykti] to bortezomib, lenalidomide, and dexamethasone [VRd]. Basically, in both the control and experimental arms, patients would get VRd for the first 6 cycles. After that, in the experimental arm, patients will get just 1 infusion of cilta-cell, then no treatment after that. There should be a long treatment-free interval, and in the control arm, they will get continuous [VRd]. CARTITUDE-5 is fully enrolled, and if it shows that a single infusion of cilta-cel after VRd induction is superior to continuous VRd, then it will impact our practice in both younger and older patients.

CARTITUDE-6 is a more contemporary trial; [it is] daratumumab [plus] VRd induction, which is the induction that we currently use. Then, patients are randomly [assigned] to either CAR-T vs transplant. That trial will take much longer to read out given the control arm is expected to do very well, so it will probably be longer before it reads out. I still don't know one way or the other whether CAR T will be superior to autologous transplant or not, but if it is, then it will replace autologous transplant for consolidation.

References

1. FDA grants third approval under the National Priority Voucher Program. News release. FDA. March 5, 2026. Accessed March 9, 2026. https://tinyurl.com/45hhbpau
2. Mateos MV, Bahlis N, Perrot A, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients (pts) with relapsed refractory multiple myeloma (RRMM): results of MajesTEC-3. Blood. 2025;146(suppl 2):LBA-6. doi:10.1182/blood-2025-LBA-6
3. Costa LJ, Bahlis NJ, Perrot A, et al. Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. 2025;394(8):739-752. doi:10.1056/NEJMoa2514663
4. TECVAYLI® monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide. News release. Johnson & Johnson. January 14, 2026. Accessed March 13, 2026. https://tinyurl.com/4unn4bn4