FDA Approves Liso-Cel Therapy for Treatment of Adult Patients With CLL, SLL

The FDA has granted an accelerated approval to lisocabtagene maraleucel (liso-cel, Breyanzi; Bristol Myers Squibb) for the treatment of adult patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously had at least 2 lines of therapy including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. The indication is approved under accelerated approval based on response rate and duration of response, and continued approval for this indication is dependent on verification and description of clinical benefit determined by confirmatory clinical trials.

Liso-cel is a CD-19-directed chimeric antigen receptor (CAR) T-cell therapy with a 4-1BB costimulatory domain that enhances the expansion and persistence of the CAR T cells. The treatment consists of the patient’s T cells which are collected to be genetically re-engineered. The CAR T cells are then administered via an infusion as a 1-time treatment for patients.

Although CLL and SLL are among the most common types of B-cell lymphoma, treatments for patients mainly consist of targeted therapies—such as BTK and BCL-2 inhibitors—and patients often experience relapse or become refractory following early-line treatments. There is currently no established standard of care for patients and few treatment options after relapsing or becoming refractory.

“CAR T-cell therapies represent a transformative treatment option for patients with certain types of blood cancers. For years, attempts to bring other CAR T-cell therapies to patients with [R/R] CLL or SLL met challenges and found little success,” said Bryan Campbell, senior vice president and head of commercial, cell therapy, Bristol Myers Squibb, in a press release. “With the approval of [liso-cel] as the first CAR T for [R/R] CLL or SLL, we are now able to offer these patients a personalized option, while further expanding access across the broadest array of B-cell malignancies to address this critical unmet need.”

The approval comes after results from an open-label, single-arm phase 1/2 clinical trial, TRANSCEND CLL 004 (NCT03331198), which evaluated liso-cel in 89 patients with R/R CLL or SLL. The phase 1 dose escalation portion of the study assessed the safety of the treatment and determined the recommended dose for the phase 2 expansion portion, which evaluated liso-cel to determine complete response (CR) rates.

The findings indicated that treatment with liso-cel resulted in a CR rate of approximately 20% (95% CI: 11.1-31.8), and among those who achieved a complete response, the median duration of response was not reached (95% CI: 15 months-NR) by the time of data cut-off. Further, for all patients who responded to the treatment, the median duration of response was 35.3 months (overall response rate = 45%; 95% CI: 32.3-57.5; 95% CI: 12.4-NR). The investigators also observed high rates of minimal residual disease (MRD) negative status in patients who were treated with liso-cel and achieved a CR, with an MRD-negativity rate of 100% in the blood (95% CI: 75.3-100) and 92.3% in the bone marrow (95% CI: 64-99.8).

“CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses, something that has historically been associated with improved long-term outcomes,” said lead investigator Tanya Siddiqi, MD, associate professor, Division of Lymphoma, City of Hope National Medical Center, in the press release.

The findings also indicated few adverse events, with any occurrences of cytokine release syndrome (CRS) and neurologic events (NEs) being low-grade in severity. However, approximately 83% of patients experienced any grade of CRS—of which 9% had grade 3 CRS—but there were no grade 4 or 5 cases of CRS reported by patients. Further, approximately 46% of patients experienced NEs, with 20% of patients reporting the severity as grade 3. There was only 1 instance of grade 4 NEs and no grade 5 occurrences.

“The FDA approval of liso-cel in [R/R] CLL and SLL after treatment with prior [BTK inhibitor] and [BCL2 inhibitor] is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission,” said Siddiqi in the press release.

Reference

Businesswire. U.S. FDA Approves Bristol Myers Squibb’s Breyanzi® as the First and Only CAR T Cell Therapy for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). News release. March 14, 2024. Accessed March 15, 2024. https://www.businesswire.com/news/home/20240313169337/en