Lisocabtagene Maraleucel Delivers Deep, Durable Efficacy in Chronic Lymphocytic Leukemia

Treatment with lisocabtagene maraleucel (Breyanzi; Bristol Myers Squibb) showed significant efficacy in adults with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), according to a primary analysis of the phase 1/2, open-label, single-arm, multicenter TRANSCEND CLL 004 study (NCT03331198).

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The study showed that at a median follow-up of 21.1 months, lisocabtagene maraleucel delivered statistically significant complete response (CR) rates in 18.4% of patients (95% CI: 8.8-32; p=0.0006), according to data that will be presented at an oral presentation (Abstract #7501) during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting. Further, investigators observed no disease progression or deaths in patients who achieved CR, with median duration of response also not reached.

CLL, one of the most common types of leukemia in adults, occurs when too many blood stem cells in the bone marrow become abnormal lymphocytes, which causes these abnormal cells to have difficulty when fighting infections. In CLL, when the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells, and platelets to provide an effective immune response. SLL is similar to CLL, as it also affects the lymphocytes; however, the cancer cells are mostly found in the lymph nodes with SLL.

Although there are several treatments available for CLL and SLL, the study authors noted that there remains a critical unmet need for additional treatment options for patients with R/R CLL or SLL, as there is no standard of care for R/R CLL or SLL after prior therapy with targeted agents, such as a Bruton tyrosine kinase inhibitor (BTKi) and BCL2 inhibitor (BCL2i). This patient population often have high-risk disease features with poor health outcomes, as well as short overall survival. Currently, the treatment options available rarely provide CR, with limited durability of response.

“For people living with relapsed or refractory CLL or SLL after treatment with BTKi and BCL2i-based regimens, there is no standard of care treatment. Achieving deep and lasting remission in this situation is challenging as most patients experience disease progression despite continuous treatment,” said lead study investigator Tanya Siddiqi, MD, associate professor, Division of Lymphoma, City of Hope National Medical Center, in a press release. “The durable complete responses observed with liso-cel in the TRANSCEND CLL 004 trial are remarkable and represent a major step in bringing a personalized, T-cell-based treatment approach delivered as a one-time infusion into clinical practice for a complex and historically incurable disease.”

TRANSCEND CLL 004 is the first multicenter trial assessing a CD19-directed chimeric antigen receptor (CAR) T-cell therapy for patients with R/R CLL after progression on a BTKi and BCL2i. The trial enrolled patients with R/R CLL or SLL who had received at least 2 prior lines of therapy, including a BTKi (n=117).

A prespecified primary efficacy analysis set (PEAS; n=49) included patients who had experienced disease progression following treatment with a BTKi and failure of BCL2i-based regimens. These patients represent a patient population with advanced and aggressive disease who were treated with the target dose of 100 x 106 CAR-positive viable T-cells of lisocabtagene maraleucel.

Across patients treated with lisocabtagene maraleucel, investigators observed high rates of undetectable minimal residual disease (uMRD) at a rate of 63.3% in the blood (95% CI: 48.3-76.6) and 59.2% in the bone marrow (95% CI: 44.2-73.0). These results were associated with an increase in progression-free survival.

The overall response rate to treatment was 42.9% (95% CI: 28.8-57.8; p=0.3931), with a median duration of response of 35.3 months (11.01-NR). Additionally, these data were consistent between the PEAS and the study’s broad patient population, such as heavily pretreated patients with a median of 5 prior lines of therapy (2–12) and high-risk disease, with a CR rate of 18.4% (95% CI: 10.9-28.1). These results demonstrate the clinical benefit of lisocabtagene maraleucel for a broad patient population with R/R CLL or SLL, according to the study authors.

Furthermore, lisocabtagene maraleucel showed a manageable safety profile in all treated patients (n=117), including subgroups of heavily pretreated patients, with no new safety signals observed. In this patient group, any grade cytokine release syndrome (CRS) occurred in 84.6% of patients, with grade 3 CRS occurring in 8.5% of patients, and no grade 4/5 CRS events reported. Additionally, any grade neurologic events (NEs) were reported in 45.3% of patients, with grade 3 NEs reported in 17.9% of patients and 1 case (0.9%) of grade 4 NE reported, while no grade 5 NEs were reported.

“Results from TRANSCEND CLL 004 reinforce our relentless commitment to bringing the potential of CAR T cell therapy to more patients and transforming the treatment and outcomes for a broad range of hematologic malignancies,” said Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb, in the press release. “[Lisocabtagene maraleucel] has shown clinically meaningful benefit across the broadest array of B-cell malignancies of any CD19-directed CAR T-cell therapy and we remain dedicated to advancing innovative treatments for some of the most difficult-to-treat diseases with high unmet need.”

Reference

Bristol Myers Squibb’s Breyanzi (lisocabtagene maraleucel) is First and Only CAR T to Deliver Deep and Durable Efficacy in Pivotal Multicenter Trial in Relapsed or Refractory Chronic Lymphocytic Leukemia, Based on Data Presented at ASCO 2023. Princeton, NJ: Bristol Myers Squibb; May 25, 2023. Accessed May 26, 2023. https://www.businesswire.com/news/home/20230524005887/en