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BsAbs in Follicular Lymphoma
Integrating Bispecific Antibodies in Follicular Lymphoma: Practical Insights on Sequencing, Safety, and Patient Selection

Released: March 31, 2026

Loretta J. Nastoupil
Loretta J. Nastoupil, MD
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Key Takeaways
  • Differences in specific binding epitopes on CD20 may bypass resistance mechanisms to prior CD20-directed therapy.
  • Early, protocol-driven toxicity management may prevent severe events requiring hospitalization.
  • Rates of ICANS with the approved CD20 bispecific antibodies are relatively low and more often described as headaches or tremor.

With the evolving treatment landscape for follicular lymphoma (FL) and approval of bispecific antibodies (BsAbs), individualized treatment plans are becoming increasingly dependent on prior therapies, remission duration, disease burden, and patient-specific factors. In this commentary, Loretta J. Nastoupil, MD, addresses questions taken from meetings held across the country at various cancer centers and provides practical considerations for integrating BsAbs into the care of patients with FL. She also highlights key management principles for real-world practice, such as baseline risk assessment, toxicity monitoring, and patient selection.

How do structural differences among the various BsAbs translate into clinical differences?
Different epitopes may inform selection when there are several approved options for the same indication. Such differences can influence target binding affinity, resistance patterns, and T-cell–mediated cytotoxicity. Type II antibodies often induce less CD20 internalization than type I, which may sustain target presence and increase activity. Resistance to CD20-targeting antibodies may arise from CD20 mutations, so sequencing CD20-targeting agents that bind different epitopes may provide some reassurance if patients are progressing on a previous CD20 therapy or have low CD20 expression. 

Is there any benefit to preemptively giving outpatients a prescription for dexamethasone to have on hand in case they start exhibiting symptoms of cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) outside of a care facility?
Each center will likely develop its own guidelines for managing patients at risk for CRS and ICANS. Personally, I think it is helpful to provide a prescription for dexamethasone to be filled prior to the first infusion with clear guidance on how and when to use it and when to notify the treating center. Early intervention may help mitigate progression to higher-grade toxicity that could require hospitalization. 

Are there specific baseline labs that should be checked before starting a BsAb in patients with FL?
BsAbs deplete B-cells. Therefore, similar to what is recommended prior to any CD20-directed therapy, I advocate for evaluating the risk of viral reactivation. It is also a good idea to check IgG levels, as hypogammaglobulinemia and the risk of infection can be associated with these therapies, and the risk may be mitigated with prophylactic IVIG. Risk for tumor lysis syndrome may be individualized and should be monitored accordingly following standard recommendations. 

How should we counsel patients regarding ICANS risk with BsAbs?
Fortunately, the rates of ICANS with the approved CD20 BsAbs are relatively low, and they are generally described more frequently as headaches or tremor. Nevertheless, it is still important to counsel patients and family members regarding the potential risk. Supportive care interventions, including corticosteroids, can be helpful at the first signs of toxicity. 

Are there patient presentation profiles that make BsAbs preferable over other regimens for patients with previously treated FL?
BsAbs may be more widely available to patients with relapsed/refractory FL or diffuse large B-cell lymphoma than cellular therapy. Therefore, larger patient populations can likely be considered for these treatments. Having these therapies available "off the shelf" without the need for leukapheresis and manufacturing may increase their exposure to patients with rapidly growing tumors or primary refractory disease. Patients still need good social support to ensure these procedures can be done safely, particularly for outpatient treatment. Thus far, these therapies appear effective in both high- and low-risk disease-specific populations. 

Does prior bendamustine exposure affect patient outcomes with subsequent BsAbs?
We currently lack robust prospective data to conclude that prior bendamustine exposure impacts subsequent BsAb outcomes. Retrospective analyses, when reported, lacked sufficient numbers to determine the impact, but thus far, no major concern is evident. Retrospective real-world data suggest that a longer duration between bendamustine exposure and T-cell–directed therapy, particularly if >9 months, does not significantly impact outcomes. Less is understood about more recent exposure. 

Your Thoughts
What questions do you have related to using BsAbs for your patients with FL that you would like to ask an expert? Do you have any experiences with BsAbs in this setting that you would like to share with the community?

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How often do you consider prescribing dexamethasone for patients with FL before their first BsAb infusion?

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