Implications of BTK Inhibitors Combined With CAR-T in R/R CLL/SLL

EP: 1.Welcome to This OncLive Peer Exchange: Highlighting Key Abstracts From ASH 2024

EP: 2.Insights From the Comparative Efficacy and Safety of Ciltacabtagene Autoleucel and Idecabtagene Vicleucel in Real-World Relapsed/Refractory Multiple Myeloma: A Retrospective Intention-to-Treat Analysis

EP: 3.Application of Real-World Evidence in Selecting CAR T in R/R MM

EP: 4.Overview of iMMagine-1 Trial: Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of R/R MM

EP: 5.Choosing Between Bispecifics and CAR T: Real-World Implications in R/R MM

EP: 6.Future of Bispecifics and CAR T in R/R MM

EP: 7.Overview of the 5-Year Follow-Up Analysis From ZUMA-5: A Phase 2 Trial of Axi-Cel in R/R Indolent NHL

EP: 8.Key Takeaways From Iopofosine I 131 in Previously Treated Patients With Waldenstrom Macroglobulinemia (WM) in the CLOVER-WaM Trial

EP: 9.Overview of the Fixed-Duration Epcoritamab + R-Mini-CHOP in Patients With Previously Untreated DLBCL Ineligible for Full-Dose R-CHOP: Updated Results from Arm 8 of the Epcore NHL-2 Trial

EP: 10.Insights From Liso-cel Combined With Ibr for R/RCLL/SLL: Primary Results From the Open-Label, Phase 1/2 Transcend CLL 004 Study

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EP: 11.Implications of BTK Inhibitors Combined With CAR-T in R/R CLL/SLL

EP: 12.Overview of ZUMA-2 Cohorts 1-3: Use of Brexu-cel in R/R MCL

EP: 13.Insights From Augmented Hyper-CVAD (AHCVAD), a Pediatric-Inspired Regimen for Adults Younger Than 50 Years With ALL

EP: 14.Key Takeaways From ASH 2024

EP: 15.Looking Into the Future of AML Treatments

EP: 16.Looking Ahead For the Treatments of R/R MM

EP: 17.Recommendations For Future Clinical Trials in R/R MM

EP: 18.Treatment and Management of MM with Amyloidosis

EP: 19.Highlighting the Key Takeaways From ASH 2024

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.