Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM )retired), MSEd
The Bottom Line:
A combination of liso-cel and ibrutinib produced deep remissions with undetectable MRD in most patients with relapsed / refractory CLL / SLL.
Who Performed the Research and Where Was it Presented:
Dr. William Wierda from The University of Texas MD Anderson Cancer Center and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting 2024.
Background:
Liso-cel is a CD19-targeted chimeric antigen receptor T-cell (CAR-T) product that is FDA-approved for use in chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL). Previous research showed that when T cells were collected from patients who were being treated with ibrutinib, the resulting CAR T cells were more potent than those from patients not on ibrutinib. Previous studies have also suggested that ibrutinib improves T-cell function in patients with CLL. In this study, researchers looked at the efficacy of a combination of ibrutinib and liso-cel for patients with relapsed / refractory CLL / SLL.
Methods and Participants:
The TRANSCEND CLL 004 study is a phase 1/2 clinical trial of liso-cel (lisocabtagene maraleucel), which is a CD19-targeted CAR-T product, in combination with ibrutinib for patients with relapsed / refractory CLL. Patients started or continued on ibrutinib therapy, and their T cells were collected. Next, the CAR-T product was made, and once it was ready, liso-cel was infused into patients. Ibrutinib therapy could continue for up to 90 days after infusion.
Results:
- In total, 56 patients received ibrutinib plus liso-cel.
- All patients had previously been treated with a BTK inhibitor. Some patients were refractory to BTK inhibitors, and some were refractory to BCL2 inhibitors.
- The overall response rate was 86%, and the complete remission rate was 45%.
- The undetectable measurable residual disease (uMRD) rate was 86% in the blood and 84% in the bone marrow.
- The median progression-free survival was 31 months.
- Low neutrophil counts (52%) and anemia (41%) were common moderate to severe side effects.
- Cytokine release syndrome (80%) and neurological events (41%) were also common. These are known side effects of immunotherapies such as CAR-T.
Conclusions:
A combination of liso-cel and ibrutinib produced deep remissions with uMRD in the majority of patients with relapsed / refractory CLL / SLL. Future analyses will be conducted to compare this combination of ibrutinib plus liso-cell cohort with another cohort who received liso-cel monotherapy.
Links and Resources:
Watch the interview on the abstract here:
You can read the ASH abstract here: Lisocabtagene Maraleucel (liso-cel) Combined with Ibrutinib (ibr) for Patients (pts) with Relapsed or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL): Primary Results from the Open-Label, Phase 1/2 Transcend CLL 004 Study
