The research provides insights into real-world CAR T-cell therapy and the use of bispecific antibodies in DLBCL

In a lecture in 42nd Annual Chemotherapy Foundation Symposiuman event hosted by Physicians’ Education Resource, LCC, Jennifer Amengual, MD, shared insights into the benefits of CAR T-cell therapy and bispecific antibodies for patients with diffuse large B-cell lymphoma (DLBCL) in a real-world treatment setting.

“With bispecific (antibodies), there are fewer upfront challenges than with CAR T-cell therapy because (bispecific antibodies) are a standard option for immunological therapy,” Amengual said in an interview with OncLive^® following her lecture.

In the interview, she discussed treatment with CAR T-cell therapy and bispecific antibodies in the real-world setting of patients with DLBCL, the differences in treatment outcomes between these agents in clinical trials and real-world populations, and differences in treatment processes between these agents.

Amengual is the Herbert Irving Assistant Professor of Medicine in the Division of Hematology and Oncology at the Herbert Irving Comprehensive Cancer Center, part of the Columbia University Irving Medical Center in New York, New York.

OncLive: What have real-world findings shown about the use of CAR T-cell therapy in patients with DLBCL?

Amengual: There have been some important real-world publications on CAR T-cell therapy in recent years. (An examined) race and ethnicity in the (United States) in real-world patients (with B-cell lymphomas, predominantly DLBCL) who had received CAR T-cell therapy and (compared these results) with Phase 1 results /2 ZUMA-1 (NCT02348216) and phase 3 ZUMA-7 trials (NCT03391466).

Most results were consistent with clinical trial data, except for some underrepresented ethnic and racial minority groups. Compared to all other ethnic groups, non-Hispanic black patients experienced a significant reduction in overall response rate (ORR), complete response rate, and progression-free survival. This could be partly due to a smaller number of patients enrolled in clinical trials with this background. There were also less favorable, although not significant, (survival outcomes) in Hispanic patients (compared to other ethnic groups). This is an underrepresented (group) in the clinical trials.

This argues that we as a country need to do a better job of incorporating clinical trials more so that we can apply these findings in the real world. As more data becomes available, we will likely find that the effects (of CAR T-cell therapy) are reasonably similar (across all patient populations), but this requires further study.

What is the benefit of CAR T-cell therapy in older patients with DLBCL?

The (oncology community) has often been hesitant to give CAR T-cell therapy to older patients. (In) a nice real-world evaluation of older patients between the ages of 65 and over 75 who received CAR T-cell therapy, the patients did well. They tend to be hospitalized for a similar number of days (as younger patients). There are not as many emergency room visits or rehospitalizations as one might fear.

The toxicities were manageable and the results were similar to what we see in clinical trials. CAR T-cell therapy is a treatment modality that has historically been underused in older patients. However, B-cell lymphoma is a disease of older patients and we should be prepared to treat these patients with CAR-T cell therapy if necessary.

What are the key considerations for bispecific antibody treatment in patients with DLBCL?

The challenge lies in coordinating stepwise dosing, which can be complicated and slightly different for each of the available bispecific agents. (Another challenge is) monitoring cytokine release syndrome (CRS); (Patients) sometimes require (hospital) admission during one of these treatments. Once patients get through the first month or so, the first or second cycle (their treatment) goes smoothly and easily, but getting through the first few weeks of treatment can be challenging.

Do real-world data with the bispecific antibody glofitamab-gxbm (Columvi) in patients with DLBCL support the widespread use of this agent?

I was encouraged by the real-world data I read about the use of the glofitamab bispecific antibody in DLBCL in relapsed patients. Two interesting studies from Taiwan and Turkey examined the compassionate use of glofitamab in DLBCL across all types of aggressive lymphomas. (These studies found that glofitamab was safe (and associated) with few grade 3 CRS events and no immune effector cell-associated neurotoxicity syndrome at all in some studies. The toxicity profile mirrored what we see in the clinical trials and there were none unexpected toxicities in the real world.

Furthermore, the effectiveness lasts. Patients in the compassionate use setting had (received) more prior lines of therapy. They tend to be sicker and have poorer performance status, and most have had (previous) autologous stem cell transplants. There was a slight decrease in ORR and overall survival (compared to the clinical trial populations), but (these results) still largely reflected what we see in the clinical trials for those who are less sick and glofitamab in received previous lines of treatment. I am encouraged by the real-world data on glofitamab.