Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd
The Bottom Line:
CAR-T therapy can provide very long remissions in a subset of patients with relapsed / refractory CLL who responded for at least one year.
Who Performed the Research and Where Was it Presented:
Dr. Benjamin Frost from the University of Pennsylvania and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024. Dr. Joseph Fraietta from the University of Pennsylvania discussed these results with Dr. Ryan Jacobs from Levine Cancer Institute.
Background:
Chimeric antigen T cell receptor (CAR-T) therapy is a cellular immune treatment that takes T cells (a type of white blood cell) from a patient’s blood and reengineers them to recognize and attack cancer cells. In the past, CAR-T therapy has not worked well for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). However, in 2024, liso-cel became the first CAR-T product approved for use in relapsed / refractory CLL / SLL, specifically for patients who have already been treated with a BTK inhibitor and a BCL2 inhibitor. There have also been reports of CAR-T therapy producing long remissions in some patients with CLL. In this study, researchers looked at long-term outcomes in patients with relapsed / refractory CLL who received CAR-T therapy and responded for at least one year.
Methods and Participants:
This study looked at long-term outcomes for patients from two clinical trials of CAR-T therapy. In one study, patients only received CD19-directed CAR-T therapy, and in the other study, patients were treated with ibrutinib before, during, and after CD19-directed CAR-T therapy. Long-term outcomes (progression-free survival, overall survival) were evaluated in patients who had achieved at least partial response without progression at one year.
Results:
- 158 patients with CLL treated with CAR-T from nine different trials were studied
- This analysis included 31 patients who responded without disease progression in the first year, with a median follow-up of 6.5 years.
- 24 of 31 patients (77%) who reached one year without disease progression remained progression-free at the time of last follow-up, including 19 of 24 patients (79%) with follow-up >5 years.
- 71% of patients achieved a complete response within one year and had significantly better long-term outcomes (overall survival and progression-free survival).
- CAR-T cells persisted in patients for several years.
- Adding ibrutinib to CAR-T cell therapy improved outcomes, including higher overall response rates (83% vs. 56%) and lower relapse rates.
Conclusions:
CAR-T therapy can provide long remissions in a subset of patients with relapsed / refractory CLL. Most patients who reach one year of progression-free survival after CAR-T infusion remain progression-free for more than 5 years without further treatment. Outcomes are even better if they have a complete response within one year. While CAR-T therapy does not work for all patients with CLL, those who do respond well to it can have very long remissions. The challenge that remains is how to increase the percentage of patients who see deep responses and can then enjoy the benefits of a durable remission.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Curing CLL: Long-Term Outcomes of Chronic Lymphocytic Leukemia Patients with at Least One Year of Response to CART-19 Therapy
