CAR T-Cell Therapy, Liso-Cel, Achieves Superior Outcomes For Patients With Hard-To-Treat Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, affecting tens of thousands of people each year in the U.S. While many patients respond well to initial treatment, some find that their cancer either returns (relapses) or doesn’t respond to treatment at all (refractory). For these patients, options have historically been limited.

Liso-Cel is a type of CAR T-cell therapy — a revolutionary approach that uses a patient’s own immune cells to fight cancer. Doctors first collect T-cells (a type of immune cell) from the patient’s blood, genetically modify them in a laboratory to recognize and attack cancer cells, and then infuse these enhanced cells back into the patient’s body. Once infused, these modified T-cells seek out and destroy cancer cells throughout the body.

Dr. Kamdar explains that in the past, the standard approach to treatment for patients who had relapsed, refractory diffuse large B-cell lymphoma who had either relapsed within a year or did not respond to other treatment was to do a stem cell transplant (if patients were eligible for transplant).

“The TRANSFORM study established [Liso-Cel] as the standard of care compared to the historical standard of care, which used to be an autotransplant,” she explains.

How Do You Know if Treatment is Working?

After finishing lymphoma treatment, hearing the words “complete remission” can bring immense relief, meaning your scans and tests show no visible signs of cancer. Yet, sometimes your doctor might mention another term: minimal residual disease (MRD). This refers to a very small number of lymphoma cells that remain hidden in the body, invisible to regular scans or routine blood tests. MRD cells are few, but their presence matters because they can potentially grow again, causing the cancer to return.

To detect MRD in lymphoma, doctors use highly sensitive tests that look deeper than regular scans. These special tests, often analyzing blood or bone marrow samples, can find even tiny traces of lymphoma cells long before symptoms or typical imaging reveal them. Identifying MRD helps doctors better understand your long-term prognosis and decide if additional treatment might be beneficial to prevent the cancer from coming back.

The study looking into Liso-Cel’s effectiveness also found that patients who underwent this treatment had MRD less frequently than those who got the previous standard of care.

“Assessment of these patients showed that despite the fact that on the standard of care arm patients did achieve MRD negativity, the MRD negativity that was achieved on the Liso-Cel arm was deeper or more durable,” Dr. Kamdar explains.

“That eventually translated into a longer event-free survival. So patients with MRD negativity [after Liso-Cel] had a much superior efficacy benefit versus patients who were MRD negative after an autotransplant arm.”

The TRANSFORM Trial: Groundbreaking Results

The TRANSFORM trial (NCT03575351) is a critical Phase III clinical study designed to evaluate the effectiveness and safety of Liso-Cel compared to the previous standard treatment (chemotherapy followed by a stem cell transplant) for patients with high-risk relapsed or refractory large B-cell lymphoma who are eligible for transplant.

In this pivotal trial, Liso-Cel showed impressive results:

• At three years, nearly half (47%) of patients treated with Liso-Cel remained disease-free compared to just 27% who received standard care.
• The median event-free survival (time without the disease progressing or worsening) was significantly better for Liso-Cel at 29 months compared to only 2.4 months with standard treatment.
• Liso-Cel significantly reduced the risk of disease progression, recurrence, or death, and demonstrated higher overall response rates compared to traditional treatments.
• Complete response rates (no detectable cancer) were consistently superior in patients receiving Liso-Cel.

These outcomes represent a remarkable step forward, making Liso-Cel the new standard of care for eligible patients.

Safety and Side Effects

Like all powerful treatments, Liso-Cel can cause side effects.

In the TRANSFORM trial:

• Common CAR T-cell therapy-related side effects included cytokine release syndrome (CRS) and neurological events. Encouragingly, these were predominantly mild to moderate and manageable, with no severe (grade 4 or 5) cases of CRS or neurological events.
• Long-term follow-up showed cytopenias (low blood cell counts) as the most frequent side effect, occurring in 9% of Liso-Cel patients compared to 5% receiving standard treatment.
• There were fewer deaths among patients receiving Liso-Cel compared to those receiving standard care, even when standard care patients later crossed over to receive Liso-Cel.
• No new toxicities or second primary malignancies emerged, reassuring patients and clinicians about the safety profile of Liso-Cel.

Getting CAR T-Cell Therapy: What to Expect

When undergoing CAR T-cell therapy, your own T-cells are collected, genetically “re-armed” in a lab to recognize the CD19 protein on lymphoma cells, multiplied, and then returned to your bloodstream as a living drug that keeps patrolling for years.

A Patient-Centered Timeline

• Week 0: Consultation, labs, imaging, and insurance authorization
• Week 1: Leukapheresis (cell collection)
• Weeks 2 – 4: Cells engineered; “bridging” chemo may be given to hold disease in check
• Week 4: Three-day lymphodepleting chemo
• Week 5: One-time CAR T infusion—plan for at least a week of close monitoring with a 24/7 caregiver
• Week 8 – 12: First scan to gauge response; many patients already feel stronger as lymphoma shrinks

Some programs now give certain products entirely as outpatients when patients live within an hour of the hospital and have strong caregiver support.

After undergoing CAR T-cell therapy, patients can expect:

• Follow-up visits every 1-3 months in year 1, then less often.
• Vaccinations (flu, COVID-19, shingles) once immune recovery is confirmed.
• Re-building stamina with gentle exercise and balanced nutrition often starts within weeks.
• Emotional health support: Ask about counseling or support groups; survivorship clinics can help navigate work or school reintegration

Who is Eligible for Liso-Cel?

Liso-Cel is FDA-approved specifically for adult patients aged 18 to 75 with large B-cell lymphoma that has returned or not responded after initial treatment, who are considered eligible for transplant.

This offers a potentially life-changing, even curative, option for patients who previously had limited successful treatment options.

Moving Forward with Hope

The TRANSFORM trial highlights the remarkable potential of Liso-Cel to significantly improve long-term outcomes and provide a new standard of care for patients facing high-risk relapsed or refractory large B-cell lymphoma. While a lymphoma diagnosis can be daunting, advancements like Liso-Cel offer meaningful hope and potentially life-changing outcomes.

Questions to Ask Your Doctor

• Am I eligible for CAR T-cell therapy as part of my treatment for non-Hodgkin’s lymphoma?
• How can CAR T-cell therapy help treat my cancer?
• What do I experience during CAR T-cell therapy?
• Are there side effects I should be aware of?
• How do I know if CAR T-cell therapy is helping my cancer?
• Can I afford CAR T-cell therapy? Is there someone on staff who can explain the costs to me?

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