/ Published Nov 6, 2025

Evaluating Efficacy of CAR T-Cell Therapy for Diffuse Large B-Cell Lymphoma

Creator: Dr. Kaique Filardi
Published: 2025-11-06T14:16:00-05:00

: Dr. Natalie Rafaeli Medical Source: Dr. Jonathon B. Cohen
Winship Cancer Institute of Emory University Written by: Dr. Kaique Filardi
University of São Paulo

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What You Should Know

CAR T-Cell Therapy doesn’t work for everyone—but when it does, it can change the entire course of large B-cell lymphoma. Roughly four in ten patients go into complete remission, and many of those remissions last for years.
For the others, a new generation of immunotherapies, led by bispecific antibodies, is giving doctors and patients hope where there used to be none.
Clinical trials are open across the country, testing these innovations. For people who relapse after CAR T-Cells, participating in one of these studies can be a way to access the most advanced therapies before they reach general use

For many people in Atlanta and beyond facing a relapse of diffuse large B-cell lymphoma (DLBCL), CAR T-Cell Therapy has emerged as a groundbreaking treatment, according to leading experts in the field of non-Hodgkin lymphoma treatment — offering real hope and, for some, the possibility of long-term remission that didn’t exist a decade ago. But, what happens when CAR T-Cell Therapy doesn’t work as expected?

“Somewhere around 35 to 40% of patients who complete CAR T-Cell Therapy will go into complete remission,” explains Dr. Jonathon Cohen, a professor of hematology and medical oncology at Emory University School of Medicine and the Winship Cancer Institute, in Atlanta, Georgia. “And at least through the amount of time that we’ve been following them will not have a recurrence.”

That’s the turning point. Those patients, in many cases, are years out from their treatment, living without evidence of lymphoma, something nearly unlikely in the era before CAR T-Cell Therapy. But, as Dr. Cohen points out, the other side of that statistic matters just as much.

“We recognize that that includes another 60% of patients who may unfortunately need additional treatment or may have to deal with this again,” Dr. Cohen adds.

What the Numbers Mean—and Why They Matter

When CAR T-Cell Therapy entered clinical use, it was tested in people who had already been through multiple regimens of chemotherapy, transplant, or both. In the pivotal ZUMA-1 study, which helped secure the first FDA approval, more than 80% of patients responded, and over half achieved a complete remission. Long-term data showed that roughly one-third remained disease-free at five years, a survival curve with a “tail,” meaning a portion of patients stayed in lasting remission far longer than historical averages.

Subsequent studies found similar outcomes across different CAR T-Cell Therapy products, each with its own nuances in side effects, manufacturing time, and durability of response. The through-line was clear: CAR T-Cell Therapy changed the survival expectations for relapsed large B-cell lymphoma.

Before CAR T-Cell Therapy, only about one in ten patients with this level of refractory disease would live a year beyond progression. Now, 35–40% are reaching years of remission, and a growing share of patients treated earlier—after just one relapse—are seeing even better outcomes.

What Happens if CAR T-Cell Therapy Does Not Work?

For the other 60%, those whose disease returns after CAR T-Cell Therapy, the story doesn’t end there. “In the current era,” Dr. Cohen says, “we have new therapies even beyond CAR T-Cell that can make a real difference.”

The most promising of these are bispecific antibodies, sometimes called BiTEs (short for bispecific T-cell engagers). These drugs act differently from CAR T-Cells. Instead of modifying your own immune cells, bispecifics are manufactured antibodies that act as a bridge between T cells and lymphoma cells, directing the body’s immune system to attack the cancer directly.

Several bispecific antibodies—such as glofitamab (Columvi), epcoritamab (Epkinly), and mosunetuzumab (Lunsumio)—have been approved in the U.S. for adults with large B-cell lymphoma who have already received multiple treatments, including CAR T-Cell Therapy when indicated. In some studies, these therapies have shown response rates of 50–60%, even among patients whose disease relapsed after CAR T-Cell Therapy, with a subset achieving durable remissions lasting many months or longer.

“These treatments are giving us options we simply didn’t have five years ago,” Dr. Cohen adds. “We can now have a frank conversation about what it means when CAR T-Cell Therapy doesn’t work, and then very quickly pivot to what comes next. And fortunately, in the current era, we have a number of therapies that we can consider that can be quite effective for patients.”

The Changing Paradigm

For a long time, a relapse after CAR T-Cells was considered almost the end of the road. That’s no longer true. Oncologists now have a growing toolkit:

Next-generation CAR T-Cells, designed to target multiple antigens or persist longer in the body.
Bispecific antibodies which can be given in outpatient settings and repeated if needed.
Antibody-drug conjugates and small-molecule inhibitors, targeting new pathways in lymphoma cells.

Each of these advances reshapes what it means to have “relapsed” DLBCL. Survival curves are stretching, remissions are lasting longer, and doctors now have multiple lines of immunotherapy to rotate through, not just one.

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Dr. Kaique Filardi is a board-certified general surgeon and gastrointestinal (GI) surgeon from the University of São Paulo. Read More