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ASH 2024 | Predictors of outcomes with CD3 x CD20 bispecific antibodies after CAR-T failure in B-cell lymphoma
Megan Melody, MD, Cancer Center of South Florida, Palm Springs, FL, comments on the efficacy and predictors of outcomes with CD3 x CD20 bispecific antibodies post-CAR T-cell failure for aggressive B-cell lymphoma. Dr Melody highlights several patient and disease characteristics of those at a higher risk of not responding to bispecific antibodies and emphasizes that survival following progression of disease after bispecific antibodies in the post-CAR T-cell setting is quite dismal. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript
Basically, CAR T-cell therapy is approved for the treatment of relapsed/refractory large B-cell lymphoma, with three CAR T-cell constructs approved in this space. However, response rates with these drugs range anywhere from 50 to 80 percent, but about 40 to 60 percent will experience disease relapse post-CAR T-cell therapy. So there have been two novel bispecific CD3 x CD20 bispecific antibodies approved in the space for relapsed/refractory large B-cell lymphoma, epcoritamab and glofitamab...
Basically, CAR T-cell therapy is approved for the treatment of relapsed/refractory large B-cell lymphoma, with three CAR T-cell constructs approved in this space. However, response rates with these drugs range anywhere from 50 to 80 percent, but about 40 to 60 percent will experience disease relapse post-CAR T-cell therapy. So there have been two novel bispecific CD3 x CD20 bispecific antibodies approved in the space for relapsed/refractory large B-cell lymphoma, epcoritamab and glofitamab. And they’ve demonstrated response rates anywhere from about 40 to 50 percent. However, in each pivotal Phase I/II clinical trial, they included about 60 patients or a small subset of patients who had previously been treated with CAR T-cell therapy. There’s limited data known about this subset of patients, including prior treatment exposure and disease characteristics. So utilizing a consortium of 14 academic institutions, we compiled data on over 830 patients treated with CAR T-cell therapy, about 50% of which who did relapse after CAR-T, and 64 patients who then went on to be treated with bispecific antibodies. We looked at patient and disease characteristics to identify patients who may be at a higher risk of not responding to bispecific antibodies. And what we found was actually that elevated LDH, bulky disease defined as greater than 10 centimeters at the time of bispecific antibody administration, early relapse, so defined as less than 90 days after CAR T-cell therapy, the presence of primary refractory disease, meaning that those patients were unable to achieve a complete response to frontline chemoimmunotherapy even prior to CAR T-cell therapy, and the presence of double-hit lymphoma by FISH, all correlated with an increased risk of, or lower response rate to bispecific antibodies. Additionally, we found that overall response rates and complete response rates actually did align with the Phase I/II pivotal clinical trials looking at epcoritamab and glofitamab. But that survival following progression of disease after bispecific antibodies in the post-CAR T-cell setting was quite dismal at about 75 days.
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