Liso-cel Earns European Approval for Relapsed/Refractory LBCL After 1 Prior Therapy

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The European Commission has approved lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HBCL), primary mediastinal large B-cell lymphoma (PMBCL), and follicular lymphoma grade 3B (FL3B) who relapsed within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy.¹

The regulatory decision was supported by data from the phase 3 TRANSFORM trial (NCT03575351), which demonstrated that liso-cel elicited statistically significant and clinically meaningful improvements in event-free survival (EFS), complete responses (CRs), and progression-free survival (PFS) compared with standard therapy comprised of salvage chemoimmunotherapy followed by high-dose chemotherapy and hematopoietic stem cell transplant (HSCT).

In a prespecified interim analysis at a median follow-up of 6.2 months, patients in the liso-cel arm experienced a median EFS of 10.1 months vs 2.3 months for those in the standard therapy arm (HR, 0.349; 95% CI, 0.229-0.530; P < .0001). The primary analysis, conducted at a median follow-up of 17.5 months, demonstrated that liso-cel produced a median EFS that was not yet reached (NR; 95% CI, 9.5-NR) compared with 2.4 months (95% CI, 2.2-4.9) for standard therapy.

“Based on results of the TRANSFORM trial, [liso-cel] provides significantly improved outcomes compared [with] the standard of care that has been in place for decades, along with a well-established safety profile, demonstrating the benefit of using a CAR T-cell therapy earlier for patients with relapsed or refractory DLBCL,” Bertram Glass, MD, TRANSFORM trial investigator and chief physician of the Department of Hematology and Stem Cell Transplantation at Helios Klinikum in Berlin, Germany, stated in a news release. “This approval represents a significant milestone for patients with continued progress toward transforming second-line treatment practice to provide a personalized treatment option that offers the potential for durable remission.”

Data from TRANSFORM previously helped support the FDA approval of liso-cel as second-line therapy for adult patients with LBCL, including DLBCL not otherwise specified (including DLBCL arising from indolent lymphoma), HBCL, PMBCL, and FL3B, in June 2022.²

The pivotal, global, randomized, multicenter phase 3 trial enrolled patients with LBCL who were primary relapsed/refractory within 12 months after first-line therapy containing a CD20-antibody and anthracycline.1

Patients were randomly assigned to receive liso-cel or standard salvage therapy consisting of rituximab (Rituxan) plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP); rituximab plus ifosfamide (Ifex), carboplatin, and etoposide (R-ICE); or rituximab plus gemcitabine, dexamethasone, and cisplatin (R-GDP) per investigators’ choice, prior to high-dose chemotherapy and HSCT.

EFS served as the trial’s primary end point. Secondary end points consisted of CR rate, PFS, overall survival, overall response rate, and duration of response.

Additional data showed that 73.9% of patients treated with liso-cel achieved a CR, compared with 43.5% of patients given standard therapy. Liso-cel generated a median PFS of NR (95% CI, 12.6-NR) vs 6.2 months (95% CI, 4.3-8.6) for standard therapy (HR, 0.400; 95% CI, 0.261-0.615; P < .0001).

Regarding safety, instances of cytokine release syndrome (CRS) and neurological adverse effects (AEs) were generally low grade, and the majority resolved quickly with standard protocols and without prophylactic steroids. Specifically, 48.9% of patients in the liso-cel arm experienced any-grade CRS, and 1% of patients had grade 3 CRS. The median time to CRS onset was 5 days (range, 1-63), and the median duration of CRS was 4 days (range, 1-16).

Any-grade neurologic AEs occurred in 10.9% of patients in the liso-cel arm, including 4.3% of patients who had a grade 3 event. The median time to onset and median duration of neurological AEs was 11 days (range, 7-17) and 4.5 days (range, 1-30), respectively.

“With [liso-cel], people in Europe living with relapsed or refractory DLBCL now have a differentiated CAR T-cell therapy option earlier in the treatment paradigm that provides long-term clinical benefit,” Anne Kerber, senior vice president and head of Cell Therapy Development at Bristol Myers Squibb, said in a news release. “This marks the approval of our third indication in Europe for our CAR T-cell therapy portfolio, underscoring our continued drive to deliver the promise of cell therapy with curative potential for more patients.”

References

1. Bristol Myers Squibb receives European Commission approval for CAR T cell therapy Breyanzi (lisocabtagene maraleucel) for relapsed or refractory large B-cell lymphoma after one prior therapy. News release. Bristol Myers Squibb. May 3, 2023. Accessed May 3, 2023. https://news.bms.com/news/details/2023/
2. US 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. Accessed May 3, 2023. https://news.bms.com/news/details/2022/