Bispecific Antibodies in Aggressive B-Cell Lymphoma: Real-World Insights and Future Directions

Summary

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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.

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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]

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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]

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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]

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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]

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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]

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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.

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

Transcript

[A]

Welcome to the American Society of Hematology Conversations with Blood Authors podcast. This episode is hosted by Dr. Laura Michaels. She discusses the real world outcomes of patients with aggressive B cell lymphoma treated with epcoritamab or Glofitamab with Dr. Taylor Brooks.

[B]

Welcome to the Bledge podcast. I'm Laura Michaels and I'm here with Dr. Taylor Brooks of the Cleveland Clinic. We're gonna discuss recent paper that he's the first author of on real world outcomes of patients with aggressive B cell lymphoma treated with coridamab or glofitamab. Sorry about that mispronunciation, Dr. Brooks. You can tell it's been a while since I've treated diffuse large B cell lymphoma as I'm not always sure how to pronounce these new therapies. Back in the day I remember about 50% of diffuse large B cell lymphoma patients would relapse or be refractory to first line therapy. Is that still the predictions? And can you talk a little bit about why it's important that bispecifics are now part of the treatment landscape for those patients?

[C]

Well, I can't hardly blame you because 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. But it is the case that we can still treat diffuse large B cell lymphoma very well with standard frontline therapies like R CHOP and chemo immunotherapy. But significant proportion of patients will still relapse. We think that maybe up to a third or a half of patients continue to relapse even after achieving a complete remission. And over the last five to 10 years, the available treatments for these patients has changed from what formerly was chemotherapy and stem cell transplant to things like CAR T cell therapy. And for patients who continue to relapse even despite these more effective, more modern treatments, bispecific antibodies have emerged as a novel class of medicines that has proven to be effective and useful in clinical trial settings. So what we attempted to do was to evaluate the real world effectiveness and safety of two bispecific antibodies, epcoritamab and glofitamab, in patients with relapsed or refractory diffused large B cell lymphoma across 21 US institutions.

[B]

How do those two agents differ from one another?

[C]

These are monoclonal antibodies targeting two targets. First is CD20, an important lymphoma cell surface marker, and the second is CD3, which is expressed on an individual's T cells. So they are slightly different from each other in their construction and their physical form, but essentially they perform the same action, which is to find malignant B cells and to bring an individual's own T cells into close proximity and to activate them to kill the B cell lymphoma.

[B]

Interesting. So in this kind of research, looking at real world evidence, what were you and your co authors interested in finding out that wasn't possible to derive from the registrational clinical trial results on these agents?

[C]

So we wanted to try to address a couple of important questions. First was how effective were epcoritamab and glofitimab in real world clinical practice and what was the safety profile of these medicines when used outside of trials? Because I think, as many people know, when patients are enrolled onto studies, the inclusion and exclusion criteria may be strict as to exclude a significant proportion of individuals who end up being treated in real world 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. And we felt that the answers to these questions could potentially help oncologists make informed decisions about treatment options and guide the management of their patients in actual practice.

[B]

Yeah, absolutely. Can you review some of the findings? What surprised you about the results? I was particularly taken by the discussion on the P53 mutated cohort.

[C]

Sure. We were able to get information from 245 patients. 156 received epcoritamab and 89 received lofitamab. About 60% of all of our patients had prior CAR T cell therapy. Almost half were what's referred to as primary refractory. Those who have never achieved any remission to their frontline therapy, which is one of the highest risk group of individuals. And almost 3/4 of patients would have been deemed ineligible for clinical trials, mostly due to comorbidities. And this was one of the main reasons why we wanted to do this, was to try to ascertain whether this more broad application of these medicines would potentially have different outcomes or different safety profiles in individuals who could not have been enrolled to the registrational studies. We found that the overall response rates for both of the medicines were quite similar to that reported in clinical studies, with about a 50% overall response rate between the two medicines and about a quarter to almost a third of patients having a complete response. But importantly, we found the survival outcomes, like progression free survival and overall survival were shorter than what was reported in the registrational studies. And 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. We looked at a number of subgroups of patients. As you mentioned, we tried to investigate patients who have TP53 mutations because of the known impact of TP53 on treatment outcomes in patients with lymphoma as well as other hematologic malignancies. And we found that about just over 90 of our patients had TP53 mutation status that was known and and that there were 25 of them who had TP53 mutations. Importantly, we found that there was no statistically significant differences in survival outcomes between these two groups of people. However, it should be noted that these were relatively small numbers of patients. 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. But this certainly serves as a NIDUS for future research in these individuals.

[B]

Is there anything that you would say just in these last couple of minutes about the unmet needs that this kind of work demonstrates to the larger community of treating physicians?

[C]

I think there's a couple of things that I would still like to see answered. First of all, our findings suggested that CD20 testing might be important when physicians are considering the use of these medicines. We found that there was a strong association between undetectable CD20 expression and poor outcomes, suggesting that pre treatment CD20 expression may be important to assess but before starting treatment with a bispecific antibody. Second, I think that it's going to be important to try to figure out how to incorporate bispecific antibodies into the treatment of the most high risk group of patients, which are patients with primary refractory disease or who progress very early after CAR T cell therapy, where we found that these individuals who had early progression after CAR T cell therapy had very poor outcomes even with bispecific antibodies. So there's a lot of ongoing studies that I think the results of, which will be very important for bispecific use, which include the combination of bispecific antibodies with chemotherapy and the combination of bispecific antibodies with other medicines like antibody drug conjugates, as well as incorporating them in earlier lines of therapy, which is ongoing as well. So these, I think will be the studies of the future for bispecific antibody use and will hopefully find other applications for a very useful and important class of medicines for these patients.

[B]

Thanks so much Dr. Brooks for participating in this podcast. Listeners can read the full paper on real world outcomes of patients with diffuse large B cell lymphoma treated with one or either of these bispecific antibodies is available in blood.

[A]

Thank you for listening to this episode of Conversations with Blood Authors. To read the articles, please visit bloodjournal.org this episode is copyrighted by the American Society of Hematology.