EU’s CHMP Recommends Liso-Cel for Approval in R/R Large B-Cell Lymphoma

The European Medicines Agency (EMA)’s Committee for Medicinal Products for Human Use (CHMP) has recommended approval of lisocabtagene maraleucel (liso-cel; Breyanzi) for adult patients with diffuse large B-cell lymphoma (LBCL), high grade B-cell lymphoma, primary mediastinal LBCL, and grade 3B follicular lymphoma previously treated with first-line chemoimmunotherapy, according to a press release from Bristol Myers Squibb.¹

"This positive CHMP opinion is an important milestone towards introducing a potential new standard of care for people in the European Union living with relapsed or refractory [LBCL] after first-line treatment, an area of critical unmet need where few patients are able to undergo or derive long-term clinical benefit from stem cell transplant," according to the manufacturers of liso-cel.

The European Commission will issue its final decision on the approval of liso-cel in this population within approximately 2 months following the CHMP’s recommendation.

Findings from the phase 3 TRANSFORM study (NCT03575351) comparing liso-cel as second-line therapy for patients with relapsed or refractory LBCL vs standard-of-care (SOC) treatment consisting of salvage chemotherapy plus high-dose chemotherapy and hematopoietic stem cell transplant (HSCT) supported the CHMP’s recommendation.

According to data presented at the 2022 American Society of Hematology (ASH) Annual Meeting, the median event-free survival (EFS) was not reached (NR; 95% CI, 9.5-NR) with liso-cel compared with 2.4 months (95% CI, 2.2-4.9) in the SOC arm (HR, 0.356; 95% CI, 0.243-0.522).2 Additionally, the 12-month EFS rates in each respective arm were 57.1% (95% CI, 47.0%-67.3%) and 22.5% (95% CI, 13.9%-31.2%) and the 18-month rates were 52.6% (95% CI, 42.3%-62.9%) and 20.8% (95% CI, 12.2%-29.5%).

“This positive CHMP opinion is an important milestone towards introducing a potential new standard of care for people in the European Union living with relapsed or refractory [LBCL] after first-line treatment, an area of critical unmet need where few patients are able to undergo or derive long-term clinical benefit from [SCT],” Anne Kerber, senior vice president of Cell Therapy Development at Bristol Myers Squibb, said in the press release.

In the global, randomized phase 3 TRANSFORM trial, patients with refractory or relapsed LBCL were randomly assigned to receive 30 mg/m² of fludarabine for lymphodepletion and 300 mg/m² of cyclophosphamide for 3 days then liso-cel or standard-of-care salvage therapy. Treatment options in the comparator arm included the investigator’s choice of rituximab (Rituxan) plus dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP); rituximab plus ifosfamide, carboplatin, and etoposide (R-ICE); or rituximab plus gemcitabine, dexamethasone, and cisplatin (R-GDP) followed by high-dose chemotherapy and HSCT.

The primary end point of the TRANSFORM trial was EFS. Secondary end points included complete response rate, progression-free survival, overall survival, overall response rate, duration of response, adverse effects, and health-related quality of life as measured with the European Organisation for Research and Treatment of Cancer - Quality of Life C30 questionnaire.

Patients between the ages of 18 and 75 years with histologically confirmed LBCL were eligible for enrollment on the trial. Additional inclusion criteria included having an ECOG performance status of 0 or 1, refractory or relapsed disease within 12 months of first-line therapy with CD20 antibodies, and adequate organ function.

Patients who were not eligible for HSCT or had plans to undergo allogenic SCT were unable to enroll on the study. Patients were also unsuitable for enrollment if they had a prior history of malignancies other than relapsed/refractory non-Hodgkin lymphoma, received any treatment with prior gene therapy products, active autoimmune disease requiring immunosuppressive therapy, or a history or presence of central nervous system pathology.

References

1. Bristol Myers Squibb receives positive CHMP opinion 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. March 31, 2023. Accessed April 5, 2023. bit.ly/40JHgIi
2. Abramson JS, Solomon SR, Arnason JE, et al. Lisocabtagene maraleucel (liso-cel) versus standard of care (soc) with salvage chemotherapy followed by autologous stem cell transplantation (asct) as second-line (2L) treatment in patients with relapsed or refractory large B-cell lymphoma (LBCL): primary analysis of the randomized, phase 3 Transform study. Blood. 2022;140(suppl 1):1581-1583. doi:10.1182/blood-2022-159702