BTKi (Bruton tyrosine kinase inhibitors) and venetoclax are now used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). However, most patients eventually acquired resistance to current treatments, emphasizing the need for new, effective treatments. The results of phase 1 dose-escalation portion of the multicenter, open-label, phase 1/2 TRANSCEND CLL 004 (NCT03331198) study of lisocabtagene maraleucel (liso-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed/refractory CLL/SLL, are presented. Patients with standard- or high-risk characteristics who had previously had 3 or 2 prior treatments, including BTKi, were given liso-cel at one of two dosage levels (50×10^6 or 100×10^6 CAR+ T cells). The primary goals of the 2018 International Workshop on CLL recommendations were safety and defining the recommended dosage; anticancer activity was exploratory.
Minimal residual disease (MRD) was determined in both blood and bone marrow. Around 23 of the 25 patients that were recruited got liso-cel and were evaluated for safety. Patients had a median of 4 (range,1-11) previous therapy (100% ibrutinib; 65% venetoclax), and 83% exhibited high-risk characteristics such as mutant TP53 and del (17p). About 74% of individuals experienced cytokine release syndrome (9% degree 3) and 39% had neurological problems (22% grade 3/4). Overall and complete responses were achieved by 82% and 45% of the 22 efficacy-evaluable patients, respectively. 75% and 65% of 20 MRD-evaluable patients obtained undetectable MRD in blood and marrow, respectively. The safety and effectiveness were comparable across dosing levels. The phase 2 section of the trial was underway with 100 × 106 CAR+ T cells.
