What You Should Know
- Chemotherapy, bispecific antibodies, antibody-drug conjugates, and newer generations of CAR T-Cells are some of the options for patients whose CAR T-Cell Therapy did not work.
- Trials today include next-generation CAR T-Cell Therapies, new bispecific antibodies, and combination regimens that aim to make remissions deeper and longer-lasting. Enrolling in a Clinical Trial might be the best option, rather than the last resort. Ask your doctor what clinical trials you could be a good fit for.
“We tell patients that roughly 35 to 40 percent of people who complete CAR T-Cell Therapy go into complete remission and may stay there for years,” explains Dr. Jonathon Cohen, a professor of hematology and medical oncology at Emory University School of Medicine and the Winship Cancer Institute.
Read MoreSet Expectations: A Conversation With Your Doctor
If you’ve had CAR T-Cell Therapy and the lymphoma returns or if it never fully responds, the most important step is to talk with your oncologist about what comes next. That conversation should be direct, detailed, and centered on the facilities and options available to you at that moment.
“Ask your doctor,” Dr. Cohen says, “Where do you usually refer patients when the lymphoma comes back? Are there centers nearby that offer transplant, CAR T-Cell Therapy, or clinical trials? What kinds of trials are available right now, and how can I find out more about them?”
RELATED: Dr. Jonathon Cohen Guide to Diffuse Large B-Cell Lymphoma Treatment
That line of questioning can open doors to specialized programs that your local hospital may not offer and might give you a sense of belonging to the decisions about your treatment. It’s also a way to make sure you’re being considered for emerging therapies.
Current Treatment Paths After CAR T-Cell Therapy
Chemotherapy remains an option, even for those who have been through multiple regimens before. Some patients respond again to platinum-based combinations or newer antibody-drug conjugates (ADCs) that deliver chemotherapy directly to lymphoma cells while sparing healthy tissue.
But, the real breakthroughs, according to Atlanta’s top oncologists, are happening in immunotherapy and cell-based research.
“The one group of treatments that’s become the most well used and the most promising are what we call the bispecific antibodies,” confirms Dr. Cohen.
Bispecific Antibodies
Bispecific antibodies (BiTEs)—a type of immunotherapy that directs the body’s immune cells to recognize and attack lymphoma cells—such as epcoritamab (Epkinly), glofitamab (Columvi), and mosunetuzumab (Lunsumio), have shown strong activity in people whose lymphoma returned after CAR T-Cell Therapy. These medications “bridge” T-cells and cancer cells, forcing the immune system to attack again, this time in a different way. In clinical studies, response rates have reached 50–60%, even in heavily pretreated patients.
How Bispecific Antibodies Are Changing Diffuse Large B-Cell Lymphoma Treatment</em
Antibody-Drug Conjugates (ADCs)
According to research conducted by leading lymphoma specialists at Memorial Sloan Kettering Cancer Center in New York and Moffitt Cancer Center in Florida, antibody-drug conjugates (ADCs) are another promising class of drugs that combine the precision of an antibody with the power of chemotherapy — allowing doctors to attack lymphoma cells more directly and effectively while limiting damage to healthy cells. Their research shows that antibody-drug conjugates like polatuzumab and loncastuximab are helping many people respond to treatment after other regimens stop working, offering new hope for patients with hard-to-treat lymphomas.
“We’re seeing at least one or two new drugs approved every year for large B-cell lymphoma,” Dr. Cohen adds. “That pace of innovation is increasing all the time. In terms of CAR T-Cells, there are some new bispecific CAR T-Cells that target more than one area on the lymphoma cell. At the same time, there are new bispecific antibodies that are being developed. There are drug antibody conjugates that are in development. There are new allogeneic off-the-shelf CAR T-Cells that are in development.”
High-dose chemotherapy followed by an allogeneic stem cell transplant—which uses blood-forming cells from a donor—might be an option if your health is good enough and a matching donor is available.
Meanwhile, the National Comprehensive Cancer Network Clinical (NCCN) Practice Guidelines in Oncology for B-cell Lymphomas has listed the targeted therapy combination of Tafasitamab-cxi (Monjuvi) and lenalidomide (Revlimid) as the preferred treatment for patients with diffuse large B-cell lymphoma (DLBCL) who cannot have a transplant when receiving second-line therapy.
Clinical Trials Deserve Attention
Clinical trials aren’t a last resort as many patients think; actually, they’re often the best option. Trials today include next-generation CAR T-Cell Therapies, new bispecific antibodies, and combination regimens that aim to make remissions deeper and longer-lasting.
Yet, as Dr. Cohen points out, access depends on where you receive care. He adds, “That’s why I encourage patients to ask directly: What kind of clinical trials are available? How can I find out more about that?”
Many major lymphoma programs now have dedicated research nurses or clinical trial navigators who can help patients match to appropriate studies. Even if you ultimately decide not to enroll, that discussion gives you a full picture of what’s possible—and what’s next.
Remember, participating in clinical trials may provide access to cutting-edge CAR T-Cell Therapies or antibody–drug conjugates that are not yet widely available.
Key Takeaways
- CAR T-Cell Therapy can be life-changing but is not guaranteed to work.
- If it fails, multiple options exist, including chemotherapy, immunotherapy, stem cell transplant, and clinical trials.
- Staying informed and asking your oncologist detailed questions is essential for accessing the best next steps.
- Make sure to have a conversation with your doctor about what you want from treatment.
- Ask your doctor about the chances of success with CAR T-Cell Therapy or other treatments, and what side effects you might experience in daily life.
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