Adding Ibrutinib to Enhance Liso-cel’s Effect Against CLL

Can adding ibrutinib make CAR T-cell therapy more effective for people with CLL? Discover promising study results and find out how you may be able to participate. 

Liso-cel’s impact when used alone for CLL 

Liso-cel (Breyanzi, BMS) is an FDA-approved CAR T-cell therapy for people with CLL who have already been treated with both a BTK inhibitor and a BCL-2 inhibitor. 

In these patients, liso-cel alone achieves a 44% overall response rate, indicating some level of cancer reduction. Among them, 20% experience a complete response, meaning their cancer cells are fully reduced, and their spleen and lymph nodes return to normal size after treatment. 

Combining liso-cel with ibrutinib for better outcomes

To enhance the effectiveness of liso-cel for CLL, William G. Wierda, MD, PhD, from M.D. Anderson Cancer Center led research efforts to combine it with ibrutinib (Imbruvica, Johnson & Johnson) in the TRANSCEND CLL 004 trial for patients with relapsed/refractory CLL/SLL. 

This decision was based on promising results seen in other CD19 CAR T-cell therapies used alongside ibrutinib. One key benefit of this combination is its ability to improve the function and expansion of CAR T-cells, which is essential for achieving and maintaining remission.

Dr. Wierda presented the trial’s encouraging results at the 2024 ASH conference. They showed: 

• Overall response rate: 86%
• Complete response rate: 45%, significantly higher than with liso-cel alone
• Undetectable minimal residual disease (uMRD4): Cancer cells were undetectable in 86% of patients’ blood samples using highly sensitive tests
• Duration of response: Among patients who responded, remission lasted an average of 41.4 months, demonstrating long-term effectiveness

The side effects reported in the study were similar to those typically seen with ibrutinib or liso-cel. These included low blood cell counts that required hospital monitoring, mild to moderate cytokine release syndrome, fatigue, headache, diarrhea, and nausea. Study specialists noted that these effects were manageable with supportive care. 

Importantly, serious heart-related side effects, which are seen with ibrutinib alone, were less frequent when it was combined with liso-cel. This suggests the combination did not increase heart risks.

Summary

The combination of liso-cel with ibrutinib showed encouraging results, with higher response rates and longer-lasting remission compared to liso-cel alone. These findings offer valuable insight for people with relapsed or refractory CLL exploring additional treatment options. 

If you're interested in this approach, review your eligibility to join the TRANSCEND CLL 004 trial or consult your CLL specialist. 

Read More CLL Treatment Advancements

Source: 

• 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