Three studies evaluating lisocabtagene maraleucel (liso-cel, Breyanzi; Bristol Myers Squibb) demonstrated the efficacy and safety of the drug for mantle cell lymphoma (MCL), relapsed or refractory (R/R) large B-cell lymphoma (LBCL), and R/R follicular lymphoma (FL). The data were shared at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, showing clinically meaningful outcomes across the B-cell malignancies.1
“This year’s ASCO is another exciting moment in the cascade of milestones for [liso-cel], our differentiated CAR T cell therapy approved for the broadest range of B-cell malignancies of any CAR T cell therapy,” Anne Kerber, MD, senior vice president and head of Late Clinical Development, Hematology, Oncology, Cell Therapy at Bristol Myers Squibb, said in a news release. “The new data being presented from our vast clinical development program are an incredible showcase of the improved outcomes and consistent safety profile [liso-cel] provides for patients with diverse types of lymphomas, offering a definitive therapy with demonstrated improved outcomes.”1
In 1 abstract, investigators shared results from the TRANSFORM (NCT03575351) study, which included 184 patients with primary refractory LBCL or relapsed disease within 12 months of first line therapy. Treatment was randomized to receive liso-cel or salvage chemotherapy followed by high-dose chemotherapy and autologous hematopoietic stem cell transplant. Liso-cel demonstrated continued improvements in event-free survival (EFS) and the secondary end points, including progression-free survival (PFS), overall response rate (ORR), and duration of response (DOR) with a median of 33.9 months of follow up.1
EFS in the liso-cel arm was 29.5 months compared with 2.4 months in the standard-of-care arm. ORR was 87% with a complete response (CR) of 74%, compared with 49% and 43%, respectively. At the time of follow up, median DOR and PFS were not reached for liso-cel and were 9.1 months and 6.2 months, respectively, with standard of care. At 26 months, the PFS rates were 50.9% and 26.5%, respectively.1
In the TRANSCEND FL (NCT04245839) study, 139 individuals were enrolled in the FL cohorts from July 14, 2020, to January 27, 2023. Of those, 130 patients received liso-cel and 124 were evaluated, according to the results of the study published in Nature Medicine. For those who received liso-cel, the median time from leukapheresis to liso-cel availability was 29 days and time to infusion was 49 days. Median follow-up was 18.9 months.2
For patients who had 3 lines of prior therapy, the ORR was 97%, with 92 of 95 responders achieving a CR and median time to response of 1 month, according to the study investigators. At the time of analysis, DOR was not reached at a median of 16.6 months, but the 12-month DOR was 82%. Median PFS was also not reached, with a 12-month PFS rate of 81%.2
Furthermore, for patients with 2 prior lines of therapy, ORR was 96%, with all individuals achieving CR. The DOR was not reached, but the 12-month DOR rate was 90%. Additionally, median PFS was not reached, but the 12-month PFS rate was 91%, according to the investigators.2
For safety, the most common grade 3 or greater treatment-emergent adverse events were neutropenia, anemia, thrombocytopenia, and febrile neutropenia.2
In the third abstract, the TRANSCEND NHL 001 (NCT02631044) trial was highlighted. Data from this trial were recently used in the approval of liso-cel for the treatment of R/R MCL for adults who received at least 2 prior lines of systemic therapy. The study included individuals aged 18 years and older with R/R MCL, confirmed with cyclin D11 expression or evidence-based cytogenetics, fluorescents in situ hybridization, or poly chain reaction.3
About The Trials
TRANSFORM
Trial: A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas (TRANSFORM)
ClinicalTrials.gov ID: NCT03575351
Sponsor: Celgene
Completion Date: October 2023
TRANSCEND FL
Trial: A Study to Evaluate the Efficacy and Safety of JCAR017 in Adult Subjects With Relapsed or Refractory Indolent B-cell Non-Hodgkin Lymphoma
ClinicalTrials.gov ID: NCT04245839
Sponsor: Celgene
Completion Date (Estimated): September 2028
TRANSCEND-NHL-001
Trial: Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma
ClinicalTrials.gov ID: NCT02631044
Sponsor: Juno Therapeutics, a Subsidiary of Celgene
Competition Date (Estimated): May 2024
In 2023, data showed that the ORR was 86.5%, with 74.3% of patients achieving CR. The median time to response was 1 month, and DOR was 13.3 months. Approximately 54% of patients had any grade cytokine release syndrome, with 3.2% having a grade 3 or higher. Neurological events were also reported in 31% of patients, with a greater 3 or higher occurring in approximately 10%.3
Liso-cel was previously granted accelerated approval for R/R FL who have received 2 or more prior lines of systemic therapy.1
Reference
1. Bristol Myers Squibb’s Breyanzi Demonstrates Clinically Meaningful Outcomes Across Broad Range of B-Cell Malignancies in New Data Presented at 2024 ASCO Annual Meeting. News release. Bristol Myers Squibb. June 3, 2024. Accessed June 3, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibbs-Breyanzi-Demonstrates-Clinically-Meaningful-Outcomes-Across-Broad-Range-of-B-Cell-Malignancies-in-New-Data-Presented-at-2024-ASCO-Annual-Meeting/default.aspx
2. Morschhauser F, Dahiya S, Palomba ML, Garcia-Sancho AM, et al. Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study. Nat Med (2024). https://doi.org/10.1038/s41591-024-02986-9
3. Gallagher A. FDA Approves Lisocabtagene Maraleucel for Treatment of Relapsed/Refractory Mantle Cell Lymphoma. Pharmacy Times. May 30, 2024. Accessed June 4, 2024. https://www.pharmacytimes.com/view/fda-approves-lisocabtagene-maraleucel-for-treatment-of-relapsed-refractory-mantle-cell-lymphoma
