FDA Grants Accelerated Approval to Liso-Cel for CLL/SLL After BTK, BCL-2 Inhibitors


The approval fills a void for patients with CLL or SLL whose disease progresses after treatment with a BTK inhibitor and a BCL-2 inhibitor; until now, there has been no standard of care.

FDA granted accelerated approval late today to lisocabtagene maraleucel, or liso-cel (Breyanzi, Bristol Myers Squibb), for use in chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL), marking the first time a chimeric antigen receptor (CAR) T-cell therapy has been approved for this condition. The approval was announced by Bristol Myers Squibb (BMS).1

Liso-cel received an expanded indication to treat patients with relapsed or refractory CLL/SLL if they have been previously treated at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (BCL-2). The approval fills a void for patients whose disease progresses after treatment with these therapies, as there has been no standard of care. A supplemental biologics license application for liso-cel in CLL/SLL was granted priority review November 9, 2023.2

Tanya Siddiqi, MD | Image credit: City of Hope

Tanya Siddiqi, MD | Image credit: City of Hope

“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,” Tanya Siddiqi, MD, lead investigator and associate professor, Division of Lymphoma, City of Hope National Medical Center, said in the BMS statement.1

“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 personalized T-cell based approach that has the potential to offer patients complete and lasting remission.”

“CAR T cell therapies represent a transformative treatment option for patients with certain types of blood cancers,” Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb, said in the statement.

“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 [liso-cel] as the first CAR T for relapsed or refractory 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.”

Approval is based on results from the pivotal phase 1/2 TRANSCEND CLL 004 trial (NCT03331198), which met its primary end point, according to data presented at the 2023 annual meeting of the American Society of Clinical Oncology.3 Patients who enrolled in the study had received at least 2 or 3 prior lines of therapy and were ineligible for or had progressed on a BTK inhibitor. After a media follow-up of 21.1 months (95% CI, 17.5-26.6), 18.4% of patients achieved a complete response; none of these patients died or saw their disease progress. The objective response rate, as determined by an independent review committee, was 47% (95% CI, 36%-58%), and the rate of undetectable minimal residual disease in the blood was 64% (95% CI, 53%-74%).

Liso-cel targets and binds to the CD19 transmembrane protein; this activates the CAR T cells and triggers their cancer-fighting activity.

Previously, liso-cel was approved to treat large B-cell lymphoma (LBCL), including diffuse LBCL not otherwise specified, high-grade B-cell lymphoma, primary mediastinal LBCL and grade 3B follicular lymphoma that is refractory to first line chemoimmunotherapy.

According to the statement from BMS, liso-cel’s approval included a boxed warning due to the possibility of cytokine release syndrome, neurological toxicity and secondary hematological malignancy. FDA is currently reviewing all 6 approved CAR T-cell therapies due to reports of secondary primary malignancy through its adverse event reporting system.


1. US 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 leukemia (SLL). News release. March 14, 2024. Accessed March 14, 2024.

2. US Food and Drug Administration accepts for priority review Bristol Myers Squibb’s application for Breyanzi (lisocabtagene maraleucel) for relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). News release. Bristol Myers Squibb. November 9, 2023. Accessed March 11, 2024.

3. Siddiqi T, Maloney DG, Kenderian S, et al. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic lymphoma (SLL): primary analysis of TRANSCEND CLL 004. J Clin Oncol. 2023;41(suppl 16):7501. doi:10.1200/JCO.2023.41.16_suppl.7501

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