Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL

• Published in: Blood 2022-03, Vol.139 (12), p.1794-1806
• Main Authors: Siddiqi, Tanya, Soumerai, Jacob D., Dorritie, Kathleen A., Stephens, Deborah M., Riedell, Peter A., Arnason, Jon, Kipps, Thomas J., Gillenwater, Heidi H., Gong, Lucy, Yang, Lin, Ogasawara, Ken, Thorpe, Jerill, Wierda, William G.
• Format: Article
• Language: English
• Subjects: Antigens, CD19; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive - adverse effects; Immunotherapy, Adoptive - methods; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Lymphoma, B-Cell - etiology; Recurrence
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2021011895

Bruton tyrosine kinase inhibitors (BTKi) and venetoclax are currently used to treat newly diagnosed and relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). However, most patients eventually develop resistance to these therapies, underscoring the need for effective new therapies. We report results of the 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. Patients with standard- or high-risk features treated with ≥3 or ≥2 prior therapies, respectively, including a BTKi, received liso-cel at 1 of 2 dose levels (50 × 106 or 100 × 106 CAR+ T cells). Primary objectives included safety and determining recommended dose; antitumor activity by 2018 International Workshop on CLL guidelines was exploratory. Minimal residual disease (MRD) was assessed in blood and marrow. Twenty-three of 25 enrolled patients received liso-cel and were evaluable for safety. Patients had a median of 4 (range, 2-11) prior therapies (100% had ibrutinib; 65% had venetoclax) and 83% had high-risk features including mutated TP53 and del(17p). Seventy-four percent of patients had cytokine release syndrome (9% grade 3) and 39% had neurological events (22% grade 3/4). Of 22 efficacy-evaluable patients, 82% and 45% achieved overall and complete responses, respectively. Of 20 MRD-evaluable patients, 75% and 65% achieved undetectable MRD in blood and marrow, respectively. Safety and efficacy were similar between dose levels. The phase 2 portion of the study is ongoing at 100 × 106 CAR+ T cells. This trial was registered at clinicaltrials.gov as NCT03331198. •Liso-cel was associated with manageable toxicities and rapid and deep responses in patients with relapsed/refractory CLL/SLL.•With successful manufacturing of liso-cel for patients with CLL/SLL and the encouraging phase 1 results, a phase 2 study is underway. [Display omitted]