The US Food and Drug Administration (FDA) has issued accelerated approval for lisocabtagene maraleucel (liso-cel), marketed as Breyanzi by Juno Therapeutics, a Bristol-Myers Squibb company, for the treatment of select adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
This historic approval represents a monumental advancement in the therapeutic armamentarium against chronic lymphocytic leukemia and small lymphocytic lymphoma. Lisocabtagene maraleucel (liso-cel), known commercially as Breyanzi, has achieved a groundbreaking feat as the inaugural chimeric antigen receptor (CAR) T-cell therapy sanctioned by regulatory authorities for individuals who have undergone a minimum of two prior lines of treatment.
This approval mandates the inclusion of prior administration of both a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor, delineating a pivotal milestone in the evolution of therapeutic strategies for relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma.
The significance of this regulatory milestone cannot be overstated, as it underscores a paradigm shift in the management of chronic lymphocytic leukemia and small lymphocytic lymphoma. By authorizing liso-cel for patients who have exhausted conventional treatment modalities, including targeted agents like BTK inhibitors and BCL-2 inhibitors, regulatory agencies have acknowledged the urgent need for innovative therapeutic approaches to address the unmet medical needs of this patient population. This approval not only validates the clinical efficacy and safety profile of liso-cel but also signifies a pivotal moment in the journey toward personalized medicine in hematological malignancies.
Liso-cel Marks a New Era in Lymphocytic Leukemia and Lymphoma Treatment: First CAR T-cell Therapy Approved for Advanced Cases
The approval of liso-cel as the first-line CAR T-cell therapy for relapsed or refractory chronic lymphocytic leukemia and small lymphocytic lymphoma underscores the growing recognition of cellular immunotherapy as a transformative modality in the oncology landscape. CAR T-cell therapy, with its ability to harness the patient’s immune system to target and eliminate cancer cells, represents a paradigm shift in cancer treatment, offering the potential for durable and potentially curative responses in patients with advanced disease.
Moreover, this regulatory approval serves as a testament to the collaborative efforts of researchers, clinicians, regulatory authorities, and industry stakeholders in advancing the field of cellular immunotherapy. The successful development and regulatory clearance of liso-cel for chronic lymphocytic leukemia and small lymphocytic lymphoma highlight the culmination of years of scientific innovation, clinical research, and regulatory diligence aimed at bringing novel therapies to patients in need.
As the first CAR T-cell therapy approved for relapsed or refractory CLL and SLL, liso-cel holds immense promise in reshaping the treatment landscape and improving outcomes for patients facing these challenging hematological malignancies. With its unique mechanism of action and demonstrated clinical efficacy, liso-cel represents a beacon of hope for patients who have exhausted standard treatment options, offering the potential for durable remissions and improved quality of life.
Lead trial investigator, Dr. Tanya Siddiqi of City of Hope in Duarte, California, hailed the FDA’s decision as a remarkable breakthrough, shifting the treatment paradigm for CLL and SLL from continuous therapy with sequential regimens to a one-time personalized T-cell-based approach. This approach offers the potential for complete and lasting remission, addressing the limited treatment options and incurable nature of these diseases.
A Milestone in CAR T-cell Therapy from TRANSCEND Study Success
Previously approved in 2021 for relapsed or refractory large B-cell lymphoma, liso-cel’s expanded indication for CLL and SLL followed a Priority Review and was based on data from the pivotal TRANSCEND CLL 004 study. In this study, 20% of patients with CLL or SLL achieved a complete response following a single infusion of liso-cel, marking a significant therapeutic breakthrough.
In the open-label, phase 1/2 TRANSCEND CLL 004 study, comprising 89 participants, patients received a single dose of liso-cel containing 90-110 x 10^6 CAR-positive viable T cells. The overall response rate was 45%, with a median duration of response of 35.3 months. Notably, among the 20% of patients achieving a complete response, the median duration of that response was not reached at the time of data cutoff, highlighting the potential for durable remissions with liso-cel therapy.
Furthermore, liso-cel demonstrated a tolerable safety profile in the study. The incidence of cytokine release syndrome (CRS) and neurologic events was predominantly low grade. CRS of any grade occurred in 83% of patients, with 9% classified as grade 3; no grade 4 or 5 events were reported. Similarly, neurologic events of any grade were observed in 46% of patients, with grade 3 events occurring in 20% of patients; no grade 4 or 5 events were reported.
Overall, the FDA’s approval of liso-cel for CLL and SLL represents a significant advancement in the field of CAR T-cell therapy, providing a promising treatment option for patients facing relapsed or refractory disease. With its proven efficacy and manageable safety profile, liso-cel has the potential to transform the treatment landscape and improve outcomes for patients with CLL and SLL.
Resource: Med Scape, March 15, 2024
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