FDA Grants Priority Review to Liso-Cel for Adults With Relapsed/Refractory LBCL


The FDA will conduct a speedy review of the supplemental biologics license application for lisocabtagene maraleucel as second-line treatment for adult patients with relapsed or refractory large B-cell lymphoma.

The FDA has accepted a supplemental biologics license application (sBLA) for lisocabtagene maraleucel (liso-cel; Breyanzi) as a potential treatment option for adult patients with relapsed or refractory large B-cell lymphoma (LBCL) after failure of frontline therapy, according to a press release issued by Bristol Myers Squibb.1

The sBLA was granted priority review with a Prescription Drug User Fee Act target action date of June 24, 2022. It is supported by data from TRANSFORM (NCT03575351), a global, randomized, multicenter clinical trial of liso-cel administered to adults with relapsed or refractory LBCL compared to the standard of care (SOC) consisting of salvage chemotherapy followed by high-dose chemotherapy plus autologous hematopoietic stem cell transplant.

“Breyanzi as a differentiated CD19-directed CAR T-cell therapy has already proven to be an important treatment option for patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy and now has the potential to be a new standard of care for patients after failure of first-line therapy, offering significantly improved outcomes beyond the current mainstay of care,” Anne Kerber, senior vice president, cell therapy development, Bristol Myers Squibb stated in a press release.

In TRANSFORM, second-line liso-cel achieved a statistically significant and clinically meaningful improvement in event-free survival (EFS), meeting the primary end point of the study. The study was also positive for 2 key secondary end points, which included a high complete response (CR) rate and an improvement in progression-free survival (PFS) compared with SOC.2

In 184 patients randomized 1:1 to an arm of liso-cel at a target dose of 100 × 106 CAR+ T cells or physician’s choice of SOC, baseline characteristics were well balanced between the arms. The median age was 60 years (range 20-74) in the liso-cel group compared with 58 years (range, 26-75) in the SOC arm. There were more males in the study (n = 105) than females (n = 79). And notably the liso-cel arm had more female patients than male patients while the SOC arm had more males than females.

Most patients in the study had an ECOG performance score of 0, and the most common non-Hodgkin lymphoma subtype amongst the patients was diffuse large B-cell lymphoma. Secondary central nervous lymphoma was common with a second-line Age-Adjusted International Prognostic Index of 0 or 1 in 60% or more of both treatment arms. In terms of prior response to therapy, more than 70% of patients in both arms were refractory.

The median EFS observed with liso-cel was 10.1 months (95% CI, 6.1-not reached [NR]) compared with only 2.3 months (95% CI, 2.2-4.3) in the SOC arm (P < .0001). At 6 months, the EFS rate was 63% (95% CI, 52.05%-74.7%) with liso-cel versus 33% (955 CI, 23.0%-43.8%) with SOC (P < .0001).

Liso-cel also achieved and ORR of 86% (95% CI, 77.0%-92.3%) which included CRs in 66% of patients (95% CI, 55.7%-75.8%). In comparison, the ORR was 48% (95% CI, 37.3%-58.5%) with a CR rate of 39% (95% CI, 29.1%-49.9%) in the SOC arm (P <.0001).

Other secondary end point explored in the study were PFS, overall survival (OS), safety and quality-of-life. The median PFS observed with liso-cel was 14.8 months (95% CI, 6.6 to not reached compared with 5.7 months (95% CI, 3.9-9.4) with SOC (P =.0001). OS data were immature at the time of the analysis. At a median follow-up of 6.2 months (range, 0.9-20.0), the median OS reported for the liso-cel arm was NR (6.6-NR) versus 16.4 months (95% CI, 11.0-NR) in the SOC arm (P = .257).

Treatment-emergent adverse events (TEAEs) were observed in all 100% of the liso-cel arm and 99% of the SOC arm. The most common nonhematologic TEAEs in the liso-cel arm versus the SOC arm were nausea (53% vs 57%, respectively), fatigue (39% vs 38%), and diarrhea (25% vs 42%). The most common cytopenia seen in the liso-cel group versus the SOC group were neutropenia (82% vs 54%, respectively), anemia (63% vs 64%), and thrombocytopenia (58% vs 68%).

TEAEs of special interest in the study were infection of grade 3 or higher occurring in 15% of the liso-cel arm compared with 21% of the SOC arm, and tumor lysis syndrome occurring in 0 patients versus 2, respectively.

In a separate quality-of-life analysis, patients treated with liso-cel had a more favorable overall least square mean changes from baseline to day 126 compared with the SOC arm in most of the domains analyzed.3

“This acceptance from the FDA brings us one step closer to delivering a practice-changing treatment for primary refractory or relapsed large B-cell lymphoma, making Breyanzi available to more patients in need, and underscores the advancements we’re making in cell therapy research to transform the lives of patients with difficult-to-treat blood cancers, including lymphoma,” added Kerber.1


1. U.S. Food and Drug Administration (FDA) accepts for priority review Bristol Myers Squibb’s supplemental biologics license application for breyanzi (lisocabtagene maraleucel) as a second-line therapy for relapsed or refractory large b-cell lymphoma. News release. Bristol Myers Squibb. February 17, 2022. Accessed February 17, 2022.

2. Kamdar M, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (car) t cell therapy, versus standard of care (soc) with salvage chemotherapy (ct) followed by autologous stem cell transplantation (asct) as second-line (2l) treatment in patients (pts) with relapsed or refractory (r/r) large b-cell lymphoma (lbcl): results from the randomized phase 3 transform study. Presented at: 2021 American Society of Hematology Annual Meeting & Exposition; December 11-14, 2021; Atlanta, GA. Abstract 91.

3. Abramson J, Solomon S, Arnason J, et al. Improved quality of life (QOL) with lisocabtagene maraleucel (liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, compared with standard of care (SOC) as second-line (2L) treatment in patients (Pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL): results from the phase 3 transform study. Presented at: 2021 ASH Annual Meeting; December 9-14, 2021; Atlanta, GA. Abstract 3845.

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