Episode Overview

Title: Bispecific Antibodies in Aggressive B-Cell Lymphoma: Real-World Insights and Future Directions
Podcast: Blood Podcast (American Society of Hematology)
Host: Dr. Laura Michaels
Guest: Dr. Taylor Brooks, Cleveland Clinic
Date: November 6, 2025

This episode delves into the real-world outcomes of patients with aggressive B-cell lymphoma treated with the bispecific antibodies epcoritamab and glofitamab. Dr. Taylor Brooks, first author of a recent multicenter study, discusses findings related to efficacy, safety, and future directions for these therapies outside the constraints of clinical trials.

Key Discussion Points and Insights

1. Shifting Treatment Landscape in Diffuse Large B-Cell Lymphoma (DLBCL)

[01:06]

• Standard frontline therapies (e.g., R-CHOP) remain effective but up to 33–50% of DLBCL patients relapse.
• Over the past 5–10 years, treatment options have shifted from traditional chemotherapy and stem cell transplants to more modern approaches like CAR T-cell therapy.
• Emergence of Bispecific Antibodies: Epcoritamab and glofitamab are now available options, showing promise particularly in patients who relapse after CAR T-cell therapy.

“Bispecific antibodies have emerged as a novel class of medicines that has proven to be effective and useful in clinical trial settings.”
— Dr. Taylor Brooks [01:51]

2. Mechanisms and Key Differences between Epcoritamab and Glofitamab

[02:27]

• Both are monoclonal antibodies targeting CD20 on B-cells and CD3 on T-cells.
• Key mechanism: Tether T-cells to malignant B-cells, triggering immune-mediated cell kill.
• Construction/formulation differences exist, but both ultimately serve the same therapeutic function.

“They find malignant B cells and bring an individual’s own T cells into close proximity and activate them to kill the B cell lymphoma.”
— Dr. Taylor Brooks [02:42]

3. The Value of Real-World Evidence

[03:02]

• Real-world data addresses limitations of clinical trials, whose strict inclusion criteria often exclude patients with comorbidities or high-risk features.
• Study across 21 US institutions focused on:
  • Comparing outcomes and safety of the two antibodies in broader patient populations
  • Factors influencing response and survival
  • Applicability of clinical trial efficacy and safety to day-to-day practice

“We also wanted to try to determine were there any differences in outcomes between these two medicines, which patient characteristics might influence treatment success or failure.”
— Dr. Taylor Brooks [03:48]

Study Findings

4. Patient Characteristics and Cohort Specifics

[04:25]

• Total: 245 patients (156 receiving epcoritamab, 89 receiving glofitamab)
• 60% had prior CAR T-cell therapy
• Nearly 50% were “primary refractory” (never responded to frontline treatment)—considered highest risk
• 3/4 would have been ineligible for clinical trials, mainly due to comorbidities

5. Efficacy and Safety Results

[05:12]

• Response Rates: ~50% overall response, 25–33% complete response — similar to clinical trial data
• Survival Outcomes: Progression-free and overall survival were shorter than in trials, likely due to broader, higher-risk population inclusion.

“We found that the overall response rates for both of the medicines were quite similar to that reported in clinical studies...But importantly, we found the survival outcomes...were shorter than what was reported in the registrational studies.”
— Dr. Taylor Brooks [05:19]

6. TP53 Mutation Subgroup Analysis

[05:54]

• Explored the impact of TP53 mutations (known negative prognostic factor).
• 90+ patients had known TP53 status; 25 with the mutation.
• No statistically significant difference in survival between TP53-mutated and wild-type patients, but numbers are small.

“If true, this might suggest that novel medicines with different mechanisms of action separate from chemotherapy might have the ability to circumvent the poor outcomes associated with p53 mutations.”
— Dr. Taylor Brooks [06:49]

Memorable Quotes and Notable Moments

• “Things are changing so fast that it is hard to keep up with the names and the medicines and how things are being used nowadays.”
  — Dr. Taylor Brooks [01:07]

• “We believe that this is because of the wider application of these medicines to patients who might have additional comorbidities or may have more difficult to treat disease.”
  — Dr. Taylor Brooks [05:46]

Important Segments & Timestamps

• DLBCL Relapse Rates and Changing Landscape: [01:06–01:51]
• Mechanisms of Action of Bispecific Antibodies: [02:27–03:02]
• Design and Purpose of Real-World Study: [03:02–03:48]
• Patient Demographics and Clinical Realities: [04:25–05:12]
• Efficacy and Survival Data: [05:12–05:46]
• TP53 Subgroup Findings: [05:54–06:49]
• Unmet Needs and Future Research: [07:09–08:55]

Unmet Needs and Future Research Directions

[07:09]

• Importance of pre-treatment CD20 expression testing: Strong link between undetectable CD20 and poor outcomes; may guide selection and sequencing of therapies.
• Primary refractory and post-CAR T-cell therapy patients: These highest-risk groups still fare poorly, highlighting the need for new strategies.
• Future trials: Combinations with chemotherapy, antibody-drug conjugates, and use in earlier lines of therapy are being explored.

“There’s a lot of ongoing studies ... combination of bispecific antibodies with chemotherapy ... with other medicines like antibody-drug conjugates, as well as incorporating them in earlier lines of therapy ... I think will be the studies of the future.”
— Dr. Taylor Brooks [08:08]

Conclusion

This discussion highlights the promise, limitations, and future potential of bispecific antibodies in relapsed/refractory DLBCL patients — especially when extending use to populations not served by clinical trials. Real-world insights and ongoing research will further shape treatment strategies for these challenging cases.

To read the full study and related articles: Visit bloodjournal.org
Copyright: American Society of Hematology