At the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, Emily C. Liang, MD, Fred Hutchinson Cancer Center, Seattle, Washington, shared data on the long-term outcomes of patients treated on a phase 1 and 2 clinical trial of CD19-targeting CAR T-cell therapy for relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).

Transcript:

Hi, my name is Emily Liang and I'm a first-year hematology oncology fellow at the University of Washington and Fred Hutchinson Cancer Center. I'm really honored to be able to present on behalf of our group the long-term outcomes of patients who are treated on our phase 1 and 2 clinical trial of CD19 CAR T-cell therapy for relapsed/refractory CLL.

CD19 CAR T-cell therapy is a promising therapy for patients with relapsed/refractory B-cell malignancies. We have previously reported high rates of measurable residual disease (MRD), negative responses in patients with relapse/refractory CLL who are treated on our institution's phase 1 and 2 clinical trial of CD19 CAR T-cell therapy. However, follow up was relatively limited. 

Here, we are reporting long-term outcomes and factors associated with duration of response. Our CAR T-cell product J-CAR014 was comprised of a 4-1BB costimulatory domain and an equal dose of CD4 to CD8 CAR T-cells.

We treated a total of 49 patients on our clinical trial and these patients tended to have high-risk disease. About 1/5 of patients had a prior history of, or current, Richter's transformation. Almost all patients had high-risk cytogenetics, and nearly all patients had intolerance to or progression on ibrutinib. The median prior lines of therapy was 5. Patients also had a high disease burden as evidenced by a CLL marrow percentage of 60% as a median, and approximately 1/4 of patients had bulky disease.

In the response-evaluable cohort of 47 patients, median follow-up was approximately 80 months or over 6.5 years. Median duration of response was 18.9 months or over 1.5 years, and, at 6 years of follow-up, 26% of patients had ongoing responses. In terms of median progression-free survival (PFS), it was approximately 9 months. However, there was a subset of patients who had progression-free survival for more than 6 years of follow-up. This suggests that CAR T-cell therapy may be curative in a subset of patients.

The median overall survival of all infused patients was just over 2 years with 1/3 alive at 6 years. To evaluate predictors of duration of response, we utilized univariate Cox regression models for over 50 predictors, including patient-related, disease-related, treatment-related, and response-related variables. We found that day 28 complete response by PET CT scan, day 28 measurable residual disease negativity, both by multi-parameter flow cytometry and next generation sequencing, as well as peak CD4 and CD8 CAR T-cell expansion and longer CAR T-cell persistence were associated with improved duration of response. 

In conclusion, we found that CD19 CAR T-cell therapy achieved high rates of MRD negative responses in patients with high-risk relapse refractory CLL. In a subset of these patients, these responses were ongoing at 6 years, suggesting that a portion of patients may be cured by CAR T-cell therapy. This project is really timely because we expect that liso-cel or lisocabtagene maraleucel, JCAR017, which utilizes a similar CAR construct, is expected to be approved by the FDA based on the Transcend CLL004 clinical trial.

Source:

Liang E C, Hirayama A V, Kimble E L, et al. Five-year follow-up update of defined-composition CD19 CAR T-cell therapy for relapsed/refractory CLL. Presented at ASCO Annual Meeting; June 2-6, 2023; Chicago, IL. Abstract 7511.