FDA approves first CAR-T cell therapy for relapsed CLL or SLL

CAR-T therapy

The US Food and Drug Administration (FDA) has granted accelerated approval of Breyanzi (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for relapsed or refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL).

It is approved in adult patients who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor.

The regulator has said that continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

In R/R CLL or SLL, Breyanzi is delivered through a treatment process which culminates in a one-time infusion with a single dose containing 90 to 110 x 106 CAR-positive viable T cells.

The product information is to include boxed warnings regarding cytokine release syndrome (CRS), neurologic toxicities, and secondary haematological malignancies.

“CAR-T cell therapies represent a transformative treatment option for patients with certain types of blood cancers,” said Bryan Campbell, Senior Vice President, Head of Commercial, Cell Therapy, Bristol Myers Squibb. “For years, attempts to bring other CAR-T cell therapies to patients with relapsed or refractory CLL or SLL met challenges and found little success. With the approval of Breyanzi as the first CAR-T for relapsed or refractory CLL or SLL, we are now able to offer these patients a personalised option, while further expanding access across the broadest array of B-cell malignancies, to address this critical unmet need.”

A one-time personalised therapy

The Phase I/II open-label, single-arm TRANSCEND CLL 004 study was the first pivotal multicentre trial to evaluate a CAR-T cell therapy in patients with relapsed or refractory CLL or SLL.

The complete response (CR) rate associated with Breyanzi treatment was 20%, though median duration of response was not reached at the time of data cut-off. Among all responders, median duration of response was 35.3 months. High rates of minimal residual disease (MRD) negative status were observed across patients treated with Breyanzi who achieved a CR, with an MRD-negativity rate of 100% in the blood and 92.3% in the bone marrow.

“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 Tanya Siddiqi, lead investigator and Associate Professor, Division of Lymphoma, City of Hope National Medical Center. “The FDA approval of liso-cel in relapsed or refractory CLL and SLL after treatment with prior BTKi and BCL2i is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalised T-cell based approach that has the potential to offer patients complete and lasting remission.”

Among 89 patients in the study treated with Breyanzi, occurrences of cytokine release syndrome (CRS) and neurologic events (NEs) were mostly low grade. Any grade CRS occurred in 83% of patients, with Grade 3 CRS occurring in 9% of patients. Any grade NEs were reported in 46% of patients, with Grade 3 NEs reported in 20% of patients and one case of Grade 4 NE reported.

Diana Spencer, Senior Digital Content Editor, DDW

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