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BCMA in Early Relapsed MM
FAQs: Targeting BCMA in Early Relapsed/Refractory Myeloma

Released: June 26, 2026

Donald Moore
Donald Moore, PharmD, BCPS, BCOP, DPLA, FCCP, FASHP
Anthony Perissinotti
Anthony Perissinotti, PharmD, BCOP
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Key Takeaways
  • For patients with relapsed/refractory MM after 1-2 prior lines of therapy, FDA-approved BCMA-targeted treatment options now include ciltacabtagene autoleucel, idecabtagene vicleucel, belantamab mafodotin (with bortezomib and dexamethasone), and teclistamab (with daratumumab).
  • Short-term use of a BCMA-directed bispecific antibody as bridging therapy does not appear to reduce the effectiveness of subsequent BCMA-directed CAR-T cell therapy.

In this commentary, Donald Moore, PharmD, BCPS, BCOP, DPLA, FCCP, FASHP, and Anthony J. Perissinotti, PharmD, BCOP, address key questions posed by the audience during a recent webinar titled “Targeting BCMA in Early Relapsed/Refractory Myeloma: What Oncology Pharmacists Need to Know Now and in the Near Future”. During this webinar, Dr Moore and Dr Perissinotti reviewed the efficacy and safety of BCMA-targeted therapies for patients with relapsed/refractory (R/R) multiple myeloma (MM) who have received 1-3 prior lines of therapy to better manage toxicities and improve patient outcomes.

How do you select from the available BCMA-directed therapies for patients with early R/R MM?

Anthony J. Perissinotti, PharmD, BCOP:
For patients with R/R MM, there are currently 3 different classes of BCMA-directed therapies: bispecific antibodies, antibody–drug conjugates, and CAR T-cell therapies. Two BCMA-directed CAR T-cell therapies are approved by the FDA for use in patients with MM. Ciltacabtagene autoleucel (cilta-cel) is approved for patients with R/R MM who have received ≥1 prior line of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), and are refractory to lenalidomide. Idecabtagene vicleucel (ide-cel) is FDA approved for patients with R/R MM after ≥2 prior lines of therapy including a PI, an IMiD, and an anti-CD38 monoclonal antibody.

Regarding the BCMA-directed bispecific antibodies, 3 are FDA approved in MM: teclistamab, elranatamab, and linvoseltamab. Teclistamab is approved by the FDA in combination with daratumumab for patients who have received ≥1 prior line of therapy, including a PI and an IMiD. It is also FDA approved as monotherapy for patients who have received ≥4 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody. Elranatamab is indicated for patients with R/R MM who have received ≥4 prior lines of therapy, including a PI, an IMiD, and an anti-CD38 monoclonal antibody. Linvoseltamab is indicated for patients with R/R MM who have received ≥4 prior lines of therapy, including a PI, an IMiD, and an anti‑CD38 monoclonal antibody.

To date, belantamab mafodotin is the only BCMA-directed antibody–drug conjugate with FDA approval for patients with R/R MM who have received 2 or more prior lines of therapy, including a PI and an IMiD. Following a previous voluntary withdrawal from the market, the FDA reinstated approval for belantamab mafodotin for use in combination with bortezomib and dexamethasone for patients with R/R MM. However, the use of belantamab mafodotin requires careful monitoring for ocular toxicities.

The treatment options for patients with early R/R MM with disease progression after 1 prior line of therapy are cilta-cel and teclistamab plus daratumumab. At my institution, our treatment goal is to get most patients with early R/R MM to receive CAR T-cell therapy if they are eligible candidates. Once the manufacturing process is complete, patients only need to receive 1 infusion of the CAR T-cells. Fortunately, we have the ability to administer CAR T-cell therapy, whereas some cancer centers do not. So, when CAR T-cell therapy is not available at a cancer center, patients need to be referred to another institution with that capability. As such, the treatment decision between a CAR T-cell therapy and a bispecific antibody may be easier to make when CAR T-cell therapy is not available and when the closest treating cancer center with this capability is perhaps far from where the patient resides. That said, now that we have 2 trials (MajesTEC-3 and MajesTEC-9) evaluating teclistamab in early R/R MM, with excellent outcomes and seemingly better tolerability than cilta-cel, this decision has become much more challenging. Therefore, potential treatment options should be discussed with patients and their caregivers, and they should be actively involved in the treatment decision-making process.

After disease progression on 2 lines of therapy, ide-cel and belantamab mafodotin are available options. As previously stated, the other agents, elranatamab and linvoseltamab, are indicated after the failure of ≥4 lines of therapy.

In the early R/R MM setting (after progression on 1 or 2 prior lines of therapy), the treatment option is usually between a CAR T-cell therapy and a bispecific antibody. Belantamab mafodotin is typically reserved until after ≥2 lines of therapy, including a PI and an IMiD. Since the manufacturing of CAR T-cells may take weeks to months, considering the time to get approval from the patient’s health insurance company and the required workups, a bispecific antibody may be used as a bridge to CAR T-cell therapy after insurance approval.

Donald Moore, PharmD, BCPS, BCOP, DPLA, FCCP, FASHP:
I agree. Treatment decisions should be made with the involvement of the patient and the caregivers after careful explanations of the benefits vs risks of each potential treatment. The treatment decision should fully consider the patient’s preferences, treatment goals, contraindications, and preexisting comorbid conditions.

In the early R/R MM setting, particularly after progression on 1 prior line of therapy, cilta-cel plays an important role, and there are many available bridging therapy options. Also, I have anecdotally found that many patients are able to tolerate cilta-cel better when used earlier in the disease course following effective bridging therapy, leading to a lower burden of disease compared with when cilta-cel is used later in the disease course when the patient has a higher burden of disease. Of note, CAR T-cell therapy usually involves hospitalization for multiple days (which may be up to 14 days), and for this reason, some patients may prefer treatment with teclistamab plus daratumumab. Also, to receive cilta-cel, the patient must be lenalidomide refractory.

In the third-line or later setting, it is important to note that belantamab mafodotin is used in combination with 2 other agents, whereas ide-cel is received as a single infusion once the CAR T-cells have been manufactured. So, appropriately sequencing these agents with the patient’s preferences and treatment goals in mind is of critical importance.

Anthony J. Perissinotti, PharmD, BCOP:
Yes, I agree. Other important factors to consider are the toxicities associated with the use of each of these agents. CAR T-cell therapies and bispecific antibodies are commonly associated with cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome. For patients receiving treatment at community centers, there is a limited capability to monitor for these associated adverse events, which in some institutions may involve hospitalization. So, for some patients receiving treatment at community centers, belantamab mafodotin may be preferred.

Does the use of a BCMA-directed bispecific antibody as bridging therapy reduce the effectiveness of BCMA-directed CAR T-cell therapy?

Anthony J. Perissinotti, PharmD, BCOP:
I think this is often oversimplified. The use of a BCMA-directed bispecific antibody as short-term bridging therapy before BCMA-directed CAR T-cell therapy does not appear to meaningfully compromise the activity of subsequent CAR T-cell therapy, based on the available data. However, this needs to be separated from the different clinical scenario of a patient who has a frank progression or relapse after receiving a highly effective BCMA-directed therapy.

In that setting, the patient’s disease has already demonstrated biologic resistance under strong therapeutic pressure. Those patients are inherently more challenging to treat, regardless of what therapy is used next. Therefore, inferior outcomes with subsequent BCMA-directed CAR T-cell therapy after relapse on a BCMA bispecific should not automatically be interpreted as evidence that CAR T-cell therapy “does not work after a bispecific antibody” or that CAR T-cell therapy must always be used first.

How do you manage infections associated with bispecific antibodies? 

Donald Moore, PharmD, BCPS, BCOP, DPLA, FCCP, FASHP:
The use of BCMA-directed bispecific antibodies leads to significant hypogammaglobulinemia as well as impaired humoral immunity. Hence, the use of antiviral prophylaxis against herpes simplex virus and varicella zoster virus is recommended for all patients. All patients should also be screened for the risk of hepatitis B virus reactivation. Colony-stimulating factor is strongly recommended for individuals with severe neutropenia. Of importance, CDC guidelines should be followed for vaccinations such as influenza, pneumococcus, or COVID-19.

At my institution, all patients receive antizoster prophylaxis with acyclovir. We also give pneumocystis prophylaxis, preferably sulfamethoxazole and trimethoprim. Alternatively, pentamidine or dapsone (after confirming that the patient does not have glucose-6-phosphate dehydrogenase deficiency) may be considered. For patients receiving teclistamab plus daratumumab, we administer monthly IVIG as primary prophylaxis against hypogammaglobulinemia to mitigate infectious complications.

It is important to note that severe viral and bacterial infections can trigger CRS. The nonrandomized phase II Optec/Optal trial evaluated the use of prophylactic tocilizumab in patients with R/R MM receiving teclistamab or talquetamab using the approved step-up treatment schedule in the outpatient setting. This study demonstrated that a single dose of prophylactic tocilizumab before step-up dose 1 of teclistamab or talquetamab lowered the incidence of CRS without impacting efficacy or safety. The Optec/Optal study has been amended to include an arm to assess the effect of prophylactic dexamethasone on the occurrence of CRS in patients receiving teclistamab (NCT05972135). It will be interesting to see the results from this arm.

Your Thoughts
What other operational challenges do you face regarding the incorporation of BCMA-directed therapies in your practice?

Coming Soon! Watch for our new Interactive Decision Support Tool for R/R MM. (https://deceraclinical.com/education/program/hematology/optimizing-bsabs-in-rr-mm/54938). With just a few clicks to answer a few quick questions about your actual or hypothetical patient, we will show you how your approach compares with treatment recommendations from 5 experts!

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