In a phase I/II study (TRANSCEND CLL 004) reported in The Lancet, Tanya Siddiqi, MD, and colleagues found evidence of activity with the CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Tanya Siddiqi, MD
Study Details
In the U.S. multicenter trial, 117 patients who had received two or more previous lines of therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor, were enrolled between January 2018 and June 2022 and treated with a single infusion of lisocabtagene maraleucel at 50 × 10⁶ (dose level 1) or 100 × 10⁶ (dose level 2 [DL2]) CAR T cells. Patients had received a median of five previous lines of therapy (interquartile range = 3–7 lines); all 117 patients had treatment failure on a BTK inhibitor, and 70 had also experienced venetoclax failure.
The primary endpoint was complete response or remission (including with incomplete marrow recovery) on independent review in efficacy-evaluable patients with previous disease progression on a BTK inhibitor and venetoclax failure (the primary efficacy analysis set) at DL2. The null hypothesis was a complete response rate of ≤ 5%.
Responses
Among 49 patients treated at DL2 with disease progression on a BTK inhibitor and venetoclax failure, 9 (18%, 95% confidence interval [CI] = 9%–32%) had complete response/remission (including with incomplete marrow recovery, P = .0006 vs null hypothesis). Partial response/remission or better was achieved in 21 patients (43%, 95% CI = 29%–58%). Median duration of complete response/remission was not reached; median duration of all objective responses was 35.3 months (95% CI = 11 months to not reached). Median progression-free survival among all 49 patients was 11.9 months (95% CI = 5.7–26.2 months), with 12- and 18-month rates of 47% and 42%. Median progression-free survival among patients with complete response/remission was not reached, with 12- and 18-month rates of 100%.
KEY POINTS
- Lisocabtagene maraleucel produced complete response/remission (including with incomplete marrow recovery) in 18% of patients with prior disease progression on BTK inhibitor therapy and venetoclax failure.
- Median duration of response among those with complete response/remission was not reached.
Adverse Events
Among all 117 patients receiving lisocabtagene maraleucel, grade ≥ 3 adverse events occurred in 92%, most commonly neutropenia (60%), anemia (52%), and thrombocytopenia (41%). Any-grade cytokine-release syndrome occurred in 85% of patients and was grade 3 in 9%; no grade 4 or 5 events were reported. Any-grade neurologic toxicity occurred in 45% of patients, with grade 3 events in 18% and a grade 4 event in 1%. One treatment-related death was observed, due to macrophage activation syndrome–hemophagocytic lymphohistiocytosis.
The investigators concluded, “A single infusion of lisocabtagene maraleucel was shown to induce complete response or remission (including with incomplete marrow recovery) in patients with relapsed or refractory CLL or SLL, including patients who had experienced disease progression on a previous BTK inhibitor and venetoclax failure. The safety profile was manageable.”
Dr. Siddiqi, of the Department of Hematology & Hematopoietic Cell Transplantation, City of Hope National Medical Center, is the corresponding author for The Lancet article.
Disclosure: The study was funded by Juno Therapeutics, a Bristol Myers Squibb Company. For full disclosures of the study authors, visit thelancet.com.
