New CAR-T Therapy Targets CD22 to Treat Follicular and Mantle Cell Lymphoma

Good news from the 66th annual American Society of Hematology conference for people living with B-cell lymphoma: a new CAR-T cell therapy is being tested in a phase 1 study for patients whose disease has returned after being treated with at least two previous therapies. 

The ongoing study will include patients with follicular lymphoma and mantle cell lymphoma. Read below to learn more about CAR-T and the promising early results of this novel therapy. 

What Is CAR-T Therapy?

Chimeric Antigen Receptor (CAR) T-cell therapy has been an important treatment option for people with mantle cell lymphoma (MCL) and follicular lymphoma (FL) who have received therapies that controlled the lymphoma for a period of time, but have relapsed or those who received multiple treatments but none of them could control the lymphoma (refractory). 

CAR-T cell therapy is a process in which your T-cells (which are part of your immune system) are modified so they can eliminate cancerous cells. After this modification, the cells are returned to your blood via infusion.

CD19-directed CAR T-cell therapy (CAR19) has led to high response rates in relapsed and refractory patients. However, its use, as all therapies do, has side effects, the most common are graft versus host disease, and the chance of lymphoma to reappear.

Researchers are now studying a new CAR T-cell therapy, CAR22, that can potentially benefit patients whose disease has stopped responding to CAR19.

New Clinical Trial With CAR22 Therapy

A clinical trial currently studies CAR22 therapy in patients whose large B-cell lymphoma returned after CAR19 therapy. In this early-phase study, 38 patients received CAR22 therapy, and the results showed that 68% of them had a positive response to treatment, with 53% achieving complete remission. Based on these encouraging results, the U.S. Food and Drug Administration (FDA) granted CAR22 a Breakthrough Therapy Designation for CAR19-resistant LBCL.

Given these findings, researchers believe CAR22 could also be an effective treatment for patients with relapsed or refractory MCL and FL, especially for those whose disease has progressed after two prior therapies. A Phase 1b trial is now underway to evaluate the safety and effectiveness of CAR22 in these patients.

At the conference, we interviewed the lead investigator of this study, Dr. Mathew Frank, who shared valuable insights from his research. 

Who Can Participate in This Study?

Patients with follicular lymphoma are eligible if they:

• Are 18 years or older
• Have been diagnosed with relapsed or refractory FL after at least two previous treatments
• Had disease progression within 24 months of starting their first chemotherapy regimen
• Previously received a CD20-targeted therapy combined with systemic treatment

Patients with mantle cell lymphoma are eligible if they:

• Are 18 years or older
• Have been diagnosed with relapsed or refractory MCL after at least two prior treatments, including a BTK inhibitor, an alkylating agent, and a CD20-targeted therapy
• Have measurable disease at the time of CAR-T infusion

Early Study Results

As of July 1, 2024, six patients have enrolled in the trial, with four already receiving CAR22 therapy. These results are early as the trial is still ongoing, and more people will hopefully enroll. 

However, the early results show the following: 

• CAR22 therapy was well tolerated, with no severe non-blood-related side effects reported.
• All four patients experienced a manageable cytokine release syndrome (CRS), a common side effect of CAR T-cell therapy, but it was manageable with standard treatments.
• No patients experienced neurotoxicity or other severe immune-related complications.
• At 28 days after receiving CAR22 therapy:
  • All four patients responded to treatment
  • Three had no signs of cancer on imaging scans
  • One patient had a partial response but showed no minimal residual disease (MRD-negative) on further testing

Researchers also found that the body accepted the CAR22 cells well, which is an important factor in the treatment’s effectiveness. As the study continues, more results from additional patients will be shared.

What’s Next?

This study is still enrolling participants and will continue to evaluate CAR22 therapy in patients with follicular lymphoma and mantle cell lymphoma. Researchers also plan to expand the study to include patients with other types of lymphoma, including:

• Hairy cell leukemia
• Lymphoplasmacytic lymphoma
• Burkitt lymphoma
• Marginal zone lymphoma

This clinical trial is under the identifier NCT06340737. If you or a loved one are interested in learning more about this study, speak with your doctor to see if participation might be an option.

Final Thoughts

CAR22 therapy is showing early signs of effectiveness for patients with follicular and mantle cell lymphoma who have relapsed after CAR19 therapy. While more research is needed, the initial results are encouraging, with all four treated patients showing a response. Ongoing studies will provide more insight into the long-term benefits and safety of this treatment.

For more information about this and other clinical trials, visit the Clinical Trial Finder, to filter according to your needs and select the best one for you, remember to always talk to your healthcare team about your treatment options.

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Source: 

• CD22-Directed CAR T-Cell Therapy Achieves Complete Remission in CD19-Directed CAR T-Cell Refractory Follicular and Mantle Cell Lymphoma