Data presented at the American Society of Hematology (ASH) annual meeting highlighted the potential of Bristol Myers Squibb's (BMS) Breyanzi (lisocabtagene maraleucel) in combination with Johnson & Johnson's (J&J) Imbruvica (ibrutinib) for patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The Phase I/II TRANSCEND CLL 004 study showcased promising results, particularly for high-risk patients who have failed Bruton's tyrosine kinase (BTK) and BCL2 inhibitors.
TRANSCEND CLL 004 Study Details
The TRANSCEND CLL 004 study involved patients taking ibrutinib for varying durations before leukapheresis and potentially continuing after CAR T cell infusion. As of the January 2024 data cutoff, half of the enrolled patients had completed or were actively participating in the study. The objective response rate (ORR) reached 86%, with a median duration of response (mDOR) of 41.4 months. Complete remission (CR) was achieved in 45% of the patients.
Secondary endpoints revealed a median progression-free survival (mPFS) of 31.4 months, while the median overall survival (mOS) was not reached. The combination therapy was generally well-tolerated, with 86% of patients experiencing a grade ≥3 treatment-related adverse event (TRAE); however, no grade 5 events were reported, and cytopenia was the most common TRAE.
Breyanzi's Market Position and Future Prospects
Breyanzi received accelerated approval earlier in 2024 for CLL/SLL treatment based on data from another TRANSCEND CLL 004 cohort, where 20% of patients achieved CR. It stands as the first CAR T cell therapy approved for CLL, specifically for patients who have progressed after BTK and BCL2 inhibitors. This patient population represents a significant unmet need in CLL management. The addition of ibrutinib aims to enhance CAR T cell efficacy by targeting BTK-expressing myeloid-derived suppressor cells, which can hinder CAR T cell function in CLL.
BMS is also investigating Breyanzi in combination with AbbVie’s BCL2 inhibitor, Venclexta (venetoclax). While this combination has shown a significant increase in CR compared to CAR T cell therapy alone, questions remain regarding the optimal duration of BTK inhibitor exposure before T cell collection and the most effective BTK inhibitor to use. The trial sponsors chose ibrutinib, a first-generation BTK inhibitor, over newer options like AstraZeneca’s Calquence (acalabrutinib) or Eli Lilly’s Jaypirca (pirtobrutinib). Breyanzi generated $364 million in sales in 2023 and is projected to reach $2.6 billion by 2030, according to GlobalData’s analyst consensus forecast.
