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CAR T and Bispecific Antibodies in RR MM
FAQs: CAR T-Cell Therapy and Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma

Released: April 28, 2026

Salyka Sengsayadeth
Salyka Sengsayadeth, MD
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Key Takeaways
  • There is no defined age cutoff for eligibility for CAR T-cell therapy for patients with relapsed/refractory multiple myeloma.
  • Patients with “borderline” organ function may be considered for CAR T-cell therapy on a case-by-case basis.
  • Teclistamab in combination with daratumumab is now approved by the FDA for patients with relapsed/refractory multiple myeloma after 1 or more previous lines of therapy, including a proteosome inhibitor and an immunomodulatory agent.

In this commentary, Salyka Sengsayadeth, MD, addresses key questions posed by the audience during a series of workshops in an education curriculum titled “Combating Myeloma: Improving Access and Outcomes With CAR T-Cell and Bispecific Antibody Therapies in Veterans With Relapsed/Refractory Multiple Myeloma”.

How do you select between idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) for your patients with relapsed/refractory (R/R) multiple myeloma (MM)
The FDA approval for cilta-cel in R/R MM was based on the results of the CARTITUDE-1 trial (after ≥3 prior lines of therapy) and the CARTITUDE-4 trial (after 1-3 prior lines of therapy) (NCT03548207, NCT04181827). In both CARTITUDE-1 and CARTITUDE-4, the 30-month overall survival (OS) rates with cilta-cel in the as-treated patient population were ≥68%. The median OS rate in CARTITUDE-1 was 60.7 months, and the median OS in CARTITUDE-4 has not yet been reached after a median follow-up of 34 months. The 30-month progression-free survival (PFS) rates were 54.2% and 68.4% in CARTITUDE-1 and CARTITUDE-4, respectively.

On the other hand, the FDA approval of ide-cel in R/R MM was based on the results of the KarMMa-3 trial for patients who had received ≥2 prior lines of therapy. In this trial, the median PFS with ide-cel was 13.8 months, and the median OS with ide-cel in the intention-to-treat population was 41.4 months after a median follow-up of 30.9 months.

With full consideration that these agents were studied in different trials with varying patient populations, from my clinical perspective, cilta-cel appears to elicit better efficacy compared with ide-cel. However, ide-cel seems to be better tolerated, especially among older and frail patients for whom neurologic adverse events are of concern. Of note, cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) are adverse events associated with CAR T-cell therapies, and the timing of onset of CRS and ICANS with ide-cel and cilta-cel are different. With ide-cel, CRS generally occurs within 1-2 days after CAR T-cell infusion, whereas with cilta-cel, CRS usually starts later, approximately 7 days after CAR T-cell infusion. This may be a concern for some patients/caregivers, and as such may contribute to the treatment choice between these 2 CAR T-cell therapies. The treatment center’s approach to monitoring CRS and ICANS can also drive treatment selection, especially if CAR T-cell therapy is administered in an outpatient setting.

Overall, it is important to carefully weigh and discuss the benefits vs the risks of each treatment option with the patients and their caregivers before making treatment recommendations. The patients’ preferences and treatment goals need to be discussed and incorporated into the decision-making process.

Is age an important factor to consider when determining eligibility for CAR T-cell therapy?
Yes, age is an important factor to consider, but there is no definitive age cutoff. If a patient meets the eligibility criteria to receive CAR T-cell therapy and is considered to be fit and otherwise healthy, CAR T-cell therapy is an option. Many centers, including the VA Tennessee Valley Healthcare System (TVHS)/Vanderbilt School of Medicine, will often consider CAR T-cell therapy for patients in their 70s and 80s if they are fit.

How do you select patients with R/R MM and borderline cardiac, renal, and pulmonary function for CAR T-cell therapy?
Most centers for CAR T-cell therapy, including the TVHS, have a set “standard of practice minimum”. However, exceptions can be made for fit patients who are otherwise healthy and who meet the criteria to receive CAR T-cell therapy. In particular, ide-cel is generally well tolerated even by patients with moderately reduced cardiac function and those with borderline renal and/or pulmonary function. Some centers will consider patients with an ejection fraction as low as 40% and those with reduced renal function for CAR T-cell therapy. Some centers will also consider some patients on dialysis if they are otherwise appropriate candidates for CAR T-cell therapy.

We will consider CAR T-cell therapy for a fit patient with borderline pulmonary function who is determined, overall, to be able to tolerate treatment. However,  we have minimum pulmonary function requirements. For instance, patients with R/R MM and an ejection fraction of <40% or those with severe lung dysfunction, such as those with a diffusing capacity of the lungs for carbon monoxide of <30%, CAR T-cell therapy is not an option.

What are the strategies that you use to reduce inpatient admissions for CRS associated with CAR T-cell therapy and bispecific antibodies?
Some centers have adopted an outpatient CRS monitoring approach for patients receiving CAR T-cell therapy. This approach incorporates vital sign monitoring and telemedicine visits to closely monitor patients and avoid potential unnecessary hospitalization. Some centers have also adopted the use of prophylactic steroids for patients, and this strategy has significantly helped to reduce inpatient admissions for CRS monitoring.

With regard to patients receiving bispecific antibodies, some cancer centers provide patients with prescriptions for dexamethasone for use in the outpatient or in-home settings. By so doing, patients have dexamethasone on hand for use as soon as symptoms of CRS are reported and appropriate vital sign monitoring indicates CRS. This approach helps to reduce inpatient admissions for CRS monitoring in many cancer centers.

Is it appropriate to switch to a different bispecific antibody after treatment failure of the previously administered bispecific antibody for patients with R/R MM?
Yes. It appears that the field is heading more towards the use of different bispecific antibody–based combinations, especially because the available and investigational bispecific antibodies have varying molecular targets. For example, teclistamab targets CD3 and BCMA and is now available for use in combination with daratumumab. On March 5, 2026, the combination of teclistamab and daratumumab received FDA approval for patients with R/R MM who have received ≥1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent. This approval was based on the results of the phase III MajesTEC-3 trial, which investigated teclistamab plus daratumumab vs daratumumab plus pomalidomide and dexamethasone or daratumumab plus bortezomib and dexamethasone for patients with R/R MM (NCT05083169). The phase III MonumenTAL-3 trial is investigating the utility of talquetamab, a bispecific antibody that targets both CD3 and GPRC5D, in combination with daratumumab with or without pomalidomide vs daratumumab plus pomalidomide and dexamethasone for patients with R/R MM (NCT05455320).

Based on encouraging results from the phase I/II trial RedirectTT-1 trial that investigated teclistamab plus talquetamab (NCT04586426), the phase III MonumenTAL-6 trial is investigating the efficacy and safety of combining talquetamab with either pomalidomide or teclistamab vs elotuzumab plus pomalidomide and dexamethasone or pomalidomide plus bortezomib and dexamethasone for patients with R/R MM who have received 1-4 prior lines of therapy including an anti-CD38 antibody and lenalidomide (NCT06208150).

So, targeting different antigens as well as switching between drug classes are effective treatment strategies in R/R MM. Finally, I am excited about the evolving treatment landscape, including ongoing investigations of another CAR T-cell therapy, anitocabtagene autocleucel, as well as other drug classes that are in the clinical pipeline for patients with R/R MM. Anitocabtagene autoleucel is particularly interesting because of its mechanism of action, which includes the use of a novel D-Domain binder that may allow for more effective treatment with less immunotoxicity based on recent promising clinical trial results.

Your Thoughts
What other questions do you have about administering CAR T-cell therapy and bispecific antibodies for patients with R/R MM in the Veterans Healthcare System? Please answer the polling question and join the conversation by submitting your questions and comments in the discussion box below.

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How often do you refer older patients with R/R MM or those with “borderline organ function” who may be eligible for CAR T-cell therapy to centers for further evaluation?

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