FDA Grants Accelerated Approval for Liso-Cel in Patients With Relapsed or Refractory Follicular Lymphoma


The indication is for adult patients who have received at least 2 prior lines of systemic therapy and is based on the response rate and duration of response shown in a phase 2 trial.

The FDA has granted an accelerated approval for lisocabtagene maraleucel (liso-cel, Breyanzi; Bristol Myers Squibb) for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have previously received 2 or more lines of systemic therapy. The accelerated approval is based on the response rate and duration of response (DOR) demonstrated in the phase 2 TRANSCEND FL trial (NCT04245839).1

Follicular lymphoma -- Image credit: Lisa | stock.adobe.com

Image credit: Lisa | stock.adobe.com

Liso-cel is a CD19-directed chimeric antigen receptor (CAR) T cell therapy that has a 4-1BB costimulatory domain that enhances the expansion and persistence of CAR T cells. The T cells in a patient’s body are collected and genetically re-engineered to become CAR T cells that are administered via infusion as a 1-time treatment. Currently, it is approved in the US for the treatment of relapsed or refractory large B-cell lymphoma (LBCL) after at least 1 prior line of therapy. It has also received an accelerated approval for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) following at least 2 prior lines of therapy.1,2

“[Liso-cel] is a cornerstone of our cell therapy portfolio, providing a differentiated profile across a wide array of B-cell malignancies,” said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb, in a press release. “Today’s [accelerated] approval of [liso-cel] for relapsed or refractory FL provides an option with potential for lasting remission in a 1-time infusion and a safety profile that allows for administration and monitoring in both the inpatient and outpatient setting in an increasing number of certified treatment centers in the US.”1

About the Trial

Trial Name: A Study to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL) (TRANSCEND FL)

ClinicalTrials.gov ID: NCT04245839

Sponsor: Celgene

Completion Date (Estimated): September 28, 2028

The approval came after the open-label, global, multicenter, single-arm phase 2 TRANSCEND FL trial which evaluated the efficacy and safety of the CAR T cell therapy, liso-cel (referred to as JCAR017 in the trial), in patients with relapsed or refractory B-cell non-Hodgkin lymphoma including FL. Patients were treated with 30 mg/m2 of intravenous (IV) fludarabine per day and 300 mg/m2 of IV cyclophosphamide per day for 3 days prior to liso-cel initiation. Liso-cel was then infused on day 1 at a target dose of 100 × 106, 2 to 7 days after completion of the chemotherapy regimen. Each liso-cel dose included CD4+ and CD8+ CAR+ T cells.1,3

The primary outcome measure was overall response rate—including best overall response of complete response (CR) or partial response as determined by a review committee—and the secondary outcome measures were CR rate, duration of response, progression-free survival, and safety. All outcomes were assessed at a follow-up of up to 60 months.1,3

According to the analysis results, patients who received treatment with liso-cel in the third-line plus setting, the overall response rate (ORR) was approximately 95.7% (95% CI: 89.5-98.8), and the CR rate was approximately 73.4% (95% CI: 63.3-82.0). Additionally, the responses were both rapid and durable in patients, with a median time to response of about 1 month (range: 0.6-3.3). The DOR was not reached (95% CI: 18.04-NR), with about 80.9% of responders remaining in response at 12 months, and 77.1% of responders remaining in response at 18 months. According to the investigators, results from the primary analysis—which were presented at the 2023 International Conference on Malignant Lymphoma—demonstrated an ORR of 97% (95% CI: 91.6-99.4; 1-sided p < .0001) in efficacy evaluable patients (n=101) with about 94% of patients achieving a CR (95% CI: 87.5-97.8; one-sided p < .0001).1

“In the treatment of relapsed or refractory FL, patients often cycle through treatments with typically shorter responses with each new line of therapy. Those who have experienced early disease progression have notably poor prognosis,” said study investigator M. Lia Palomba, MD, lymphoma and cell therapy specialist, Memorial Sloan Kettering Cancer Center, in the press release. “The FDA [accelerated] approval of [liso-cel] for patients with relapsed or refractory FL is an important advancement in addressing an ongoing unmet need in the FL treatment paradigm, providing patients a new option that has shown remarkably high response rates and an established safety profile.”1

Previously, liso-cel was granted an accelerated approval for the treatment of adult patients with relapsed or refractory CLL or SLL who had received at least 2 prior lines of therapy, including a Bruton tyrosine kinase inhibitor and a B-cell lymphoma 2 inhibitor. This approval came after findings from the open-label, single-arm phase 1/2 TRANSCEND CLL 004 clinical trial (NCT03331198), which included a phase 1 dose escalation portion to assess the safety of liso-cel treatment and determine the recommended dose for the phase 2 expansion.2

The findings for this trial demonstrated a CR rate of approximately 20% (95% CI: 11.1-31.8), and among those who achieved a CR, the median DOR was not reached (95% CI: 15 months-NR) by the time of data cut-off. For those who responded to liso-cel, the median DOR was 35.3 months (ORR = 45%; 95% CI: 32.3-57.5; 95% CI: 12.4-NR). Further, there were also high rates of minimal residual disease negative status in patients who achieved a CR, with a negativity rate of 100% in the blood (95% CI: 75.3-100) and 92.3% in the bone marrow (95% CI: 64-99.8).2

In the TRANSCEND FL trial, approximately 53% of patients experienced any grade cytokine release syndrome (CRS), of which 4% reported a severity of grade 3 or higher. Additionally, any grade neurologic events (NEs) occurred in approximately 31% of patients, with grade 3 or higher occurring in 10% of patients. Similarly to TRANSCEND FL, patients in the TRANSCEND CLL 004 trial also experienced CRS and NEs, which occurred in 83% and 46% of patients, respectively. Further, both grade 3 CRS (9%) and NEs (20%) were present, however, there were no instances of grades 4 or 5 CRS and only 1 occurrence of grade 4 NEs.1,2

“The lymphoma community has felt an urgent need for advancements in the treatment of relapsed or refractory follicular lymphoma,” said Meghan Gutierrez, CEO, Lymphoma Research Foundation, in the press release. “The approval of [liso-cel] offers patients a new and meaningful treatment option that provides hope for lasting remission, and we are grateful to those who have contributed to this exciting milestone for patients.”1

  1. Bristol Myers Squibb. Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi Approved by the U.S. Food and Drug Administration for Relapsed or Refractory Follicular Lymphoma. News release. May 15, 2024. Accessed May 16, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzi-Approved-by-the-U.S.-Food-and-Drug-Administration-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx
  2. McGovern, G. FDA Approves Liso-Cel Therapy for Treatment of Adult Patients With CLL, SLL. Pharmacy Times. March 15, 2024. Accessed May 16, 2024. https://www.pharmacytimes.com/view/fda-approves-liso-cel-therapy-for-treatment-of-adult-patients-with-cll-sll
  3. A Study to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma (NHL) (TRANSCEND FL). ClinicalTrials.gov identifier: NCT04245839. Updated November 30, 2023. Accessed May 16, 2024. https://clinicaltrials.gov/study/NCT04245839
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