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BsAbs in MM
A Quick Guide to Bispecific Antibodies for the Treatment of Relapsed/Refractory Multiple Myeloma

Released: September 24, 2024

Expiration: September 23, 2025

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Key Takeaways
  • In recent years, we have seen an expansion of the treatment armamentarium for multiple myeloma, including the approval of bispecific antibodies in the relapsed/refractory setting.
  • With key toxicities including infection and neurotoxicity, multidisciplinary care of patients receiving bispecific antibodies for myeloma is essential.

Currently, 3 bispecific antibodies are approved for relapsed/refractory (R/R) multiple myeloma (MM), with 2 therapies (elranatamab and teclistamab) directed at BCMA and 1 (talquetamab) targeting GPRC5D. All are indicated after 4 or more prior lines of therapy including a proteasome inhibitor, immunomodulatory drug, and CD38 monoclonal antibody. In this commentary, Caitlin Costello, MD, answers key questions related to the current role of bispecific antibodies in the treatment of R/R MM, notable toxicities, the importance of multidisciplinary care, and how the treatment of myeloma is evolving.

Are there any particular challenges you are currently facing in clinical practice regarding the implementation of bispecific antibodies for the treatment of MM?

The greatest challenge with bispecific antibodies is ensuring that this therapy is an option for all eligible patients, which encompasses logistics and supportive care. Administering the bispecific antibodies in the safest way when patients are at risk for novel toxicities, such as cytokine-release syndrome (CRS) and neurotoxicity, is a challenge that most clinics face, in particular for clinics and hospitals that are already experiencing significant strain on their resources because of high patient volume, limited staffing, or other logistical challenges. The second consideration is how to ensure a careful balance between effective therapies that decrease the burden of MM while keeping patients safe from adverse effects such as infections, dysgeusia, and hair and nail changes, which are toxicities that are commonly seen with these different targeted bispecific antibodies.

What are some factors that you consider when deciding among bispecific antibodies?

The greatest factors that we consider when choosing among available bispecific antibodies are: (1) the target antigen, (2) the associated toxicity, and (3) efficacy. We want to provide the safest therapies that are most effective while recognizing the toxicities that are relevant to each individual medication and select the optimal treatment for each individual patient.

How are you sequencing bispecific antibodies, including with other therapies such as CAR T-cell therapy?

As with any relapse, we consider specific criteria when selecting the next line of therapy. This includes the patient’s medical comorbidities, the biology of the disease as it relapsed, any prior therapy-related toxicities, and social dynamics. When we take into consideration all of those factors, in the ideal setting, we think that CAR T-cell therapy administered first followed by bispecific antibody therapy second makes the most sense biologically. However, when looking at any individual patient’s pattern of relapse, we sometimes do not have the luxury of choice and need to intervene quickly with a treatment such as a bispecific antibody when we may not be able to wait for CAR T-cell manufacturing time.

Which toxicities are most important to highlight with use of bispecific antibodies?

The toxicities associated with bispecific antibodies are specific to the antigen that is being targeted. We know that BCMA-targeted bispecific therapies carry the highest risk of infections in addition to the known CRS and low but real risk of neurotoxicity that can be seen with any bispecific antibody. By contrast, talquetamab, a GPRC5D-directed T-cell engager, is known for its on-target, off-tumor effects on hair, skin, taste buds, and nails that can lead to a different toxicity profile including dysgeusia and hair and nail changes.

What is the role of multidisciplinary care teams, including infectious disease, emergency medicine, and neurology, in the management of patients receiving bispecific antibodies for MM?

The incorporation of multiple care teams is paramount to successful treatment with bispecific antibodies. We know that patients receiving these therapies can develop adverse effects that may require them to be admitted to the hospital, may require them to be seen by our critical care teams, and may require the expertise of our neurology or infectious disease specialists to help manage some of these adverse effects. Because some of the adverse effects of therapy can be so all-reaching across different disease specialties, having a multidisciplinary approach to patient care is critical for patients with MM receiving bispecific antibodies.

Are there any upcoming data that you are looking forward to?

There are many ongoing trials exploring combination approaches with bispecific antibodies together (RedirecTT-1 [NCT04586426]) and also in combination with other commonly used treatments such as pomalidomide or bortezomib (MonumenTAL-3 [NCT05455320]; MonumenTAL-6 [NCT06208150]), for example. I think combination therapies will be of great interest in MM, in particular as we see bispecific antibodies moving to earlier lines of therapy.

How do you see the treatment of MM evolving in the near future?

Treatment for MM continues to evolve as we aim to determine the optimal sequence and therapy for each patient so that we can administer treatments that allow for deep and durable responses and someday offer patients treatment-free intervals.

For more information on the use of bispecific antibodies for the treatment of MM, please check back as more information is added: “Refining Therapeutic Approaches in R/R MM: Expert Guidance on Bispecific Antibody Therapy Optimization.”

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