Unpacking Key Data from ASH 2024 - Episode 11
Implications of BTK Inhibitors Combined With CAR-T in R/R CLL/SLL
Panelists discuss how the combination of lisocabtagene maraleucel (liso-cel) and ibrutinib in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), as presented in the phase 1/2 TRANSCEND CLL 004 study, may redefine treatment strategies by highlighting the potential benefits of combining chimeric antigen receptor (CAR) T-cell therapy with targeted agents and reshaping perspectives on sequential vs combination approaches in high-risk CLL.
Video content above is prompted by the following:
Combination of Lisocabtagene Maraleucel (Liso-cel) and Ibrutinib in R/R CLL/SLL – Primary Results from TRANSCEND CLL 004
The TRANSCEND CLL 004 study (phase 1/2) evaluates the combination of lisocabtagene maraleucel (liso-cel), a CD19-directed CAR T-cell therapy, and ibrutinib, a BTK inhibitor, in patients with R/R CLL or SLL. Given the challenges in treating high-risk CLL, this combination aims to enhance disease control and improve the depth of response.
Key Findings
- Enhanced Efficacy: The combination demonstrated promising response rates in a population with high-risk features, potentially overcoming resistance mechanisms observed with single-agent therapies.
- Tolerability and Safety: Although CAR T-cell therapy alone is associated with cytokine release syndrome and neurotoxicity, the addition of ibrutinib may help modulate immune-related toxicities, improving tolerability.
- Potential Paradigm Shift: These results challenge the conventional sequential approach of BTK inhibitors followed by CAR T-cell therapy, suggesting that combining these modalities earlier may yield superior outcomes.
Clinical Implications
- New Treatment Strategy: The synergy between ibrutinib and CAR T-cell therapy could redefine treatment sequencing in high-risk CLL, favoring combination approaches over stepwise escalation.
- Personalized Therapy: Identifying which patients benefit most from early combination therapy vs sequential treatment will be critical.
- Future Directions: Further studies are needed to establish the optimal duration of ibrutinib before and after CAR T-cell infusion and to assess long-term remission durability.
This study highlights the transformative potential of integrating BTK inhibition with cellular therapy, paving the way for new strategies in high-risk CLL management.
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