Bristol Myers Squibb was granted accelerated approval by the U.S. FDA for Breyanzi  (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy. 
 
This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). 
 
In R/R CLL or SLL, Breyanzi is delivered through a treatment process which culminates in a one-time infusion with a single dose containing 90 to 110 x 106 CAR-positive viable T cells. 
 
CLL and SLL are among the most common types of B-cell lymphoma. Treatments for people living with CLL or SLL primarily consist of targeted therapies including BTK- and BCL-2 inhibitors. However, patients often experience relapse or become refractory following early-line treatment with these therapies and there is no established standard of care for patients with double-class exposed CLL or SLL. After relapsing or becoming refractory to these therapies, patients have few options and poor outcomes, including lack of durable complete responses.
 
The Phase 1/2 TRANSCEND CLL 004 study was the first pivotal multicenter trial to evaluate a CAR T cell therapy in patients with relapsed or refractory CLL or SLL. The complete response (CR) rate associated with Breyanzi treatment was 20%. Among patients who achieved a CR, median duration of response was not reached at the time of data cutoff. Among all responders, median duration of response was 35.3 months. High rates of minimal residual disease (MRD) negative status were observed across patients treated with Breyanzi who achieved a CR, with an MRD-negativity rate of 100% in the blood and 92.3% in the bone marrow.
 
Among 89 patients in the study treated with Breyanzi, occurrences of cytokine release syndrome (CRS) and neurologic events (NEs) were mostly low grade. Any grade CRS occurred in 83% of patients, with Grade 3 CRS occurring in 9% of patients. No Grade 4/5 CRS events were reported. Any grade NEs were reported in 46% of patients, with Grade 3 NEs reported in 20% of patients and one case of Grade 4 NE reported. No Grade 5 NEs were reported.