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Liso-Cel Approved for Second-Line Large B-Cell Lymphoma

The approval builds off of liso-cel's (Breyanzi) previous indication for third-line or later treatment in LBCL.

The FDA has approved Bristol Myers Squibb’s supplemental biologics license application for lisocabtagene maraleucel (liso-cel; Breyanzi) as second-line therapy for patients with large B-cell lymphoma (LBCL).1

The chimeric antigen receptor (CAR) T-cell therapy was originally approved in February 2021 for adults with relapsed or refractory diffuse LBCL who have not responded to at least 2 other treatments based off data from the pivotal phase 3 TRANSFORM (NCT03575351) trial.2

In the second-line setting, liso-cel recently showed good efficacy and patient-reported outcome (PRO) data in the phase 2 TRANSCEND study (NCT03483103), updated data from which were presented at the 2022 American Society of Clinical Oncology (ASCO) meeting, held June 3-7, 2022, in Chicago, Illinois.3,4

The TRANSCEND study dosed 61 participants that had disease that relapsed after or was refractory to first-line chemotherapy. These participants were followed-up for a median of 12.3 months (range, 1.2–26.5). Investigators found that overall response rate (ORR) was 80% and complete response rate (CR) was 54%. Median duration of response (DOR) was 12.1 months, progression-free survival (PFS) was 9.0 months, and median overall survival (OS) has not been reached.

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Investigators assessed PROs and found that completion rates were high (≥ 80%) across most visits for all measures. Baseline European Organisation for Research and Treatment of Cancer Quality of Life of Cancer Patients (EORTC QLQ-C30) mean fatigue scores were worse by at least 10 points at baseline compared to a general noncancer population. These scores, along with pain domain scores, Functional Assessment of Cancer Therapy – lymphoma subscale, and EuroQol Visual Analogue Scale scores improved significantly by least square means through day 545. 

Patients also reported that lymphoma symptoms improved in a clinically meaningful way. No outcomes significantly worsened and 70% of patients demonstrated meaningful improvement in FACT-LymS at month 6. 

Liso-cel has been well-tolerated, with treatment-emergent adverse events (TEAE) in TRANSCEND that included neutropenia (51%), fatigue (39%), and CRS (38%), including 1 case of grade 3 CRS (2%). Neurological events occurred in 31% of participants, 5% (n = 3) of which were grade 3 cases. AEs resolved with the use of tocilizumab (7%), corticosteroids (3%), or both (20%). Overall, grade 3 TEAEs occurred in 79% of participants, with grade 5 cases in 2 patients due to COVID-19. Two patients (3%) had grade 3/4 infections and 15 (25%) had at least grade 3 neutropenia at Day 29.

Liso-cel's supplemental biologics license application received priority review in February 2021.5 The therapy was also approved by the EMA in April 2022 for the treatment of relapsed/refractory DLBCL, primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B) in patients who have received 2 or more lines of systemic treatment.6

REFERENCES
1.U.S. FDA Approves Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi® for Relapsed or Refractory Large B-cell Lymphoma After One Prior Therapy. News release. Bristol Myers Squibb. June 24, 2022. https://news.bms.com/news/details/2022/U.S.-FDA-Approves-Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzifor-Relapsed-or-Refractory-Large-B-cell-Lymphoma-After-One-Prior-Therapy/default.aspx
2. FDA Approves New Treatment For Adults With Relapsed Or Refractory Large-B-Cell Lymphoma. News release. FDA. February 5, 2021. https://www.prnewswire.com/news-releases/fda-approves-new-treatment-for-adults-with-relapsed-or-refractory-large-b-cell-lymphoma-301223275.html
3. Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagenemaraleucel (liso-cel) as second-line (2L) therapy for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Primary analysis from the phase 2 PILOT study. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022, Chicago, Illinois. Abstract #7062
4. Gordon LI, Hoda D, Shi L, et al. Lisocabtagenemaraleucel (liso-cel) as second-line (2L) treatment (tx) for R/R large B-cell lymphoma (LBCL) in patients (pt) not intended for hematopoietic stem cell transplantation (HSCT): Patient-reported outcomes (PRO) from the phase 2 PILOT study. Presented at: 2022 ASCO Annual Meeting, June 3-7, 2022, Chicago, Illinois. Abstract #6567
5. US Food and Drug Administration (FDA) accepts for priority review Bristol Myers Squibb’s supplemental biologics license application for Breyanzi (lisocabtagenemaraleucel) 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. https://bit.ly/3Bujynp
6. Bristol Myers Squibb receives European Commission approval for CAR T cell therapy Breyanzi (lisocabtagenemaraleucel) for certain forms of relapsed or refractory large B-cell lymphoma. News release. Bristol Myers Squibb. April 5, 2022. Accessed April 8, 2022. https://bit.ly/3LPwb0l