Bispecific Antibody Use After CAR-T Failure for B-Cell Lymphoma | Megan Melody, MD, MS | #ASH24

Hi, my name is Megan Melody and I'm an assistant professor at the University of South Florida, Tampa General Hospital Cancer Institute. And I actually, this year we'll be presenting data stemming from a consortium of 14 institutions led by Northwestern University. Through this consortium, we examined 830 patients treated with CAR T-cell therapy, about 50% of whom have experienced disease relapse after CAR T-cell therapy, which is in line with the pivotal clinical trials examining this therapy for the management of relapse or refractory large B-cell lymphoma. And about 64 of these patients went on to receive bispecific antibodies, either Glofidimab, Epcaridimab or mozonituzumab. And we looked at clinical and patient characteristics and variables in order to determine factors that may impact response to therapy in the post-CAR T-cell setting. Obviously, patients who are relapsing after CAR T-cell therapy have seen at least two pretty intensive lines of therapy. And so these patients, you know, were really optimistic that we can even get their disease under control with further lines of therapy. And bispecific antibodies were actually shown to be effective in this setting with complete response rates of about 35%, which is in line with the pivotal phase one to clinical trials examining Epcaridimab and Glofidimab in this setting. So the main side effects we get concerned about for bispecific antibodies is a syndrome called cytokine release syndrome, which is a hyperinflammatory syndrome that can cause low blood pressure, hypoxia and fevers, as well as ICANS, which is a neurotoxicity which can cause confusion and tremors and sometimes more severe side effects. The good news is that with the role of bispecific antibodies or the application of bispecific antibodies in the post-CAR T-cell setting, there was actually a very, very low rate of both CRS and ICANS and no severe grade or greater than grade three toxicity seen at all. So this was actually one of our primary points in our conclusion of this abstract. And there were actually a few factors based mostly on the patient's disease that impacted whether or not a patient may be quite as responsive to bispecific antibodies and compared to patients without these factors. And so those factors included the presence of a lot of disease burden or what we call bulky disease, which is a tumor greater than 10 centimeters at the time of bispecific antibody administration, an elevated LDH, which is a serum laboratory test we check that can sometimes tell us how active the lymphoma is turning over. The presence of something called double hit lymphoma, which is a genetic test we look for that is a characteristic of the lymphoma. And then two things about sort of the response to therapy. So patients who are unable to achieve a response to frontline chemoimmunotherapy, so even prior to CAR T-cell therapy, those patients were less likely to respond to bispecific antibodies as well in the post-CAR T-cell setting. And those patients who are unable to achieve a response or who relapse within 90 days post-CAR T-cell therapy, those patients were also less likely to respond well to bispecific antibodies. These characteristics just kind of confer a more aggressive disease. I think it's really important to consider the patient themselves. These patients, when we're talking about bispecific antibodies in the post-CAR T-cell setting, that means that these patients have most likely seen at least six cycles of frontline chemoimmunotherapy, most of these patients have. Then they've been hospitalized for a month or two for CAR T-cell therapy. And now we're asking them to come back and forth to the hospital and often as a major academic center for treatment frequently with these bispecific antibodies. And so I think just simply the logistics is often difficult. I think the other thing that we definitely need to look more into are infection rates post-CAR specific antibodies in the post-CAR T-cell setting, but this was not something our abstract actually examined. But knowing that CAR T-cell therapy itself can be very immunosuppressive and reduce a patient's ability to produce immunoglobulins and fight infection. And now we're giving a subsequent therapy in this setting that can also do that. I think logically we know that these patients are at risk for pretty severe infections and this is something I'm very passionate about investigating in the future. I think bispecific antibodies is a really wonderful and novel therapy that's been developed. I think honestly within the next few years this abstract may be a little irrelevant as bispecific antibodies move into the frontline therapy and I'm very excited that my patients are going to be exposed to T-cell engaging therapies sooner to the time of diagnosis as I think that this is a really, really helpful treatment modality that offers our patients a better chance of cure.