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A single infusion of the chimeric antigen receptor (CAR) T-cell product lisocabtagene maraleucel (liso-cel; Breyanzi) was shown to induce complete response or remission in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), the phase I/II TRANSCEND CLL 004 trial showed.

In a primary efficacy analysis involving 49 patients, the complete response or remission rate (including with incomplete marrow recovery) was a statistically significant 18% (95% CI 9-32, P=0.0006), reported Tanya Siddiqi, MD, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

These 49 patients had progressed on previous Bruton tyrosine kinase (BTK) inhibitors and experienced venetoclax (Venclexta) failure, making them "double refractory," and had been treated at the recommended phase II dose level of 100×10⁶ CAR-positive T cells, they noted in .

Looking at key secondary endpoints, the overall response rate was 43%, which was not statistically significant compared with the null hypothesis (P=0.39). Median progression-free survival was 11.9 months (95% CI 5.7-26.2), and median overall survival was 30.3 months (95% CI 11.2 to not reached), while the undetectable minimal residual disease rate was 63% in blood and 59% in marrow.

Liso-cel's safety profile was "manageable," the authors said, with low rates of grade ≥3 cytokine release syndrome (CRS) and neurotoxicity.

"Liso-cel has the potential to fill a gap in the treatment landscape for patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who have experienced disease progression on previous BTK inhibitor and venetoclax failure," Siddiqi and colleagues wrote. "Whereas most current and emerging therapies target BTK, BCL2, PI3K, or anti-CD20 with continuous treatment, unlike current therapies, liso-cel is a one-time infusion that does not require continuous treatment."

"In this patient population that has exhausted all standard therapies and has limited treatment options available, liso-cel has shown a positive benefit-risk profile," they added.

According to Siddiqi and colleagues, BTK inhibitors, PI3K inhibitors, and BCL2 inhibitors alone or combined with a CD20 monoclonal antibody have shown efficacy in CLL and SLL.

"However," they noted, "patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who experience intolerance to or disease progression after BTK inhibitor and BCL2 inhibitor treatment have no established standard of care and poor outcomes, indicating a crucial unmet need."

Specifically, they pointed out that heavily pretreated patients with high-risk features have low complete response or remission rates (0-5%), with short median overall survival.

was an open-label, single-arm study conducted in the U.S. that included 117 adults with relapsed or refractory CLL or SLL who had at least two previous lines of therapy, including a BTK inhibitor. They received liso-cel at one of two dose levels: 50×10⁶ or 100×10⁶ CAR-positive T cells.

The median age of the full study population was 65 years, and 68% were men. Patients had a median of five prior lines of therapy, 44% had bulky lymph nodes, and 83% had high-risk cytogenetics. All 117 patients had prior exposure to BTK inhibitors, and 80% had received prior venetoclax. Of these, 60% had progressed on BTK inhibitors and had venetoclax failure.

After exclusions, the total efficacy analysis included 87 patients treated at a dose level of 100×10⁶ CAR-positive T cells, with 49 patients evaluable.

Among the 49 patients, median time to first response was 1.2 months and 3.0 months for complete response or remission, respectively. Median duration of response was 35.3 months, and median duration of complete response or remission (including with incomplete marrow recovery) was not reached.

In the full efficacy subset, outcomes were consistent with those in the primary efficacy analysis set.

In the full safety set of 117 patients, 92% experienced grade ≥3 treatment-emergent adverse events (TEAEs), with the most common including neutropenia (61%), anemia (52%), and thrombocytopenia (41%). Of the five deaths that were due to TEAEs, one was considered related to liso-cel.

Ten patients had grade 3 CRS, and no grade 4 or 5 CRS occurred. Grade 3 neurological events were reported in 18% of patients, and only 1% had a grade 4 neurological event.

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