Research Provides Insights Into Real-World CAR T-Cell Therapy and Bispecific Antibody Use in DLBCL

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

“With bispecific [antibodies], there are fewer challenges up front than with CAR T-cell therapy, as [bispecific antibodies are] an off-the-shelf option for immunologic-type therapy,” Amengual said in an interview with OncLive^® following her presentation.

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

Amengual serves as 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 has real-world evidence shown about the use of CAR T-cell therapy in patients with DLBCL?

Amengual: There have been a few important real-world publications about CAR T-cell therapy in the past few years. [One evaluated] race and ethnicity across the [United States] in real-world patients [with B-cell lymphomas, predominantly DLBCL] who had received CAR T-cell therapy and [compared those findings] with results from the phase 1/2 ZUMA-1 [NCT02348216] and phase 3 ZUMA-7 [NCT03391466] trials.

Most of the results held up against the clinical trial data, with exceptions in some underrepresented and minority ethnic and racial groups. There was a significant reduction in the overall response rate [ORR] and complete response rate, as well as progression-free survival, in patients of non-Hispanic Black heritage compared with all other ethnic groups. This could be in part due to a reduced number of patients that were enrolled with that background in clinical trials. There [were also less favorable], although not significant, [survival outcomes] in Hispanic patients [compared with other ethnic groups]. This is an underrepresented [group] in the clinical trials.

This speaks to [the fact that] we need to do a better job as a country in being more inclusive in clinical trials, so we can apply those findings through the real-world. As more data come out, [we will likely see] that the effects [of CAR T-cell therapy] are somewhat similar [across patient populations] but this needs to be studied further.

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

The [oncology community has often had] hesitation when giving CAR T-cell therapy in elderly patients. [In] a nice real-world evaluation of elderly patients between the ages of 65 and over 75 years of age who received CAR T-cell therapy, patients did well. They tend to be admitted [to the hospital] for a similar number of days [as younger patients]. They don’t have so many emergency department visits or rehospitalizations as one might be worried about.

The toxicities were manageable, and outcomes were similar to what we see in clinical trials. CAR T-cell therapy is a treatment modality that historically has been underused in older patients. That said, B-cell lymphoma is a disease of older patients, and we should be prepared to treat those patients with CAR T-cell therapy if it’s appropriate.

What are key treatment considerations regarding bispecific antibodies for patients with DLBCL?

The challenges lie in coordinating step-up dosing, which can be complicated and is slightly different for each of the bispecific agents out there. [Another challenge is] monitoring for cytokine release syndrome [CRS]; [patients] sometimes require [hospital] admission during one of those treatment administrations. When patients get through the first month or so, the first cycle or 2, [their treatment] becomes smooth and easy but getting through those 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’ve read about the use of the glofitamab bispecific antibody for DLBCL in the relapsed setting. Two interesting studies out of Taiwan and Turkey investigated compassionate use for glofitamab in DLBCL across all different kinds of aggressive lymphomas. [These trials found that glofitamab was] safe [and associated] with few grade 3 CRS events in some studies and no immune effector cell–associated neurotoxicity syndrome whatsoever. The toxicity [profile] mirrored what we see in the clinical trials, with no unexpected toxicities in the real world.

Furthermore, the efficacy holds up. The patients in the compassionate-use setting had [received] more prior lines of therapy. They tend to be sicker with a poorer performance status, and most had [received prior] autologous stem cell transplants. There was a slight reduction in ORR and overall survival [compared with the clinical trial populations] but [these outcomes] still closely mirrored what we see in the clinical trials for those who are less sick and receiving glofitamab in earlier lines of treatment. I feel encouraged by the real-world data with glofitamab.