Lisocabtagene Maraleucel, a CD19-Directed CAR T-Cell Therapy

In this study, named TRANSCEND CLL 004, lisocabtagene maraleucel (liso-cel), an investigational chimeric antigen receptor (CAR) T-cell product for patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) was evaluated.

Eligible patients had received at least 2 or 3 prior lines of therapy for CLL or SLL, based on their risk status. High-risk disease includes those with del(17p), TP53 mutation, unmutated IGHV, or complex karyotype. Prior therapy included a Bruton’s tyrosine kinase inhibitor unless its use was contraindicated.

At the time of analysis, 23 patients with relapsed or refractory CLL/SLL were assessed for product safety and 22 patients were assessed for efficacy. Their median age was 66 years. Most (83%) patients had high-risk CLL/SLL and had received a median of 5 prior therapies, including ibrutinib.

Following 3 days of chemotherapy (fludarabine and cyclophosphamide), patients received an infusion of liso-cel. Two dose levels were tested. Nine patients were treated using the lower dose of liso-cel and 14 patients were treated using the higher dose.

The most common serious side effects that were reported by patients receiving liso-cel were low white and red blood-cell counts. Two patients had severe infusion reactions and 9 patients had severe neurologic events, including brain disorders.

After median follow-up of 11 months, 82% of evaluable patients responded to liso-cel. Complete responses, including those with incomplete blood count recovery, were seen in 46% of patients. Ten of 12 responders who have been followed for 9 months or more have remained progression-free. In most patients, responses deepened over time. Among 20 patients who were tested for minimal residual disease, most became undetectable.

Researchers concluded that, in patients with CLL/SLL who had several previous lines of therapy, the side effects, possible infusion reactions, and neurologic events seen with liso-cel were manageable. Complete responses and undetectable minimal residual disease were rapidly achieved and have lasted for more than 6 months. The next portion of the TRANSCEND CLL 004 trial is currently enrolling patients using the higher dose level of liso-cel.

Abstract 503. ASH 2019.