The decision, which aligns with its indication in the US, was based on efficacy and safety results from Bristol Myers Squibb’s TRANSFORM clinical trial in forms of large B-cell lymphoma.
Bristol Myers Squibb’s lisocabtagene maraleucel (liso-cel; Breyanzi), a marketed CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy, has been approved by the European Commission in all EU member states for the treatment of adult patients with diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal LBCL (PMBCL), and follicular lymphoma grade 3B (FL3B) whose disease relapsed within 12 months from the completion of first-line chemoimmunotherapy or those whose disease is refractory to first-line chemoimmunotherapy.1
The new approval expands the eligible patient population for liso-cel in the EU, which previously included adult patients with relapsed/refractory (r/r) DLBCL, PMBCL, and FL3B who have received 2 or more lines of systemic treatment.2 The decision was based on positive results from the phase 3 TRANSFORM clinical trial (NCT03575351) which evaluated liso-cel against standard of care (SOC) salvage immunochemotherapy followed by high-dose chemotherapy and hematopoietic stem cell transplant. At the time of a prespecified interim analysis, with a median follow-up of 6.2 months patients treated with liso-cel had a median event-free survival (EFS) of 10.1 months; by comparison, patients treated with SOC had a median EFS of 2.3 months (HR, 0.349; 95% CI, 0.229-0.530; P <.0001).
Furthermore, the results of the primary analysis for TRANSFORM included the finding that at a median follow-up of 17.5 months, the median EFS was not reached for patients treated with liso-cel, whereas the median EFS for patients receiving SOC was 2.4 months (95% CI: 2.2-4.9). In addition, patients treated with liso-cel achieved a complete response (CR) rate of 73.9%, whereas 43.5% achieved a CR after receiving SOC. In terms of safety, 48.9% of patients treated with liso-cel in TRANSFORM experienced cytokine release syndrome (CRS), with 1% experiencing grade 3 cases of CRS; and 10.9% of patients treated with liso-cel experienced neurologic events, with 4.3% experiencing grade 3 cases.
“Based on results of the TRANSFORM trial, Breyanzi provides significantly improved outcomes compared to 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, a TRANSFORM trial investigator and the chief physician of the Department of Hematology and Stem Cell Transplantation at Helios Klinikum, in Berlin, Germany, said in a statement.1 “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.”
Liso-cel is also being investigated in ongoing clinical trials for several other indications. On May 1, 2023, Bristol Myers Squibb announced that liso-cel had met the primary end point of overall response rate (ORR) in 2 separate clinical trials for patients with r/r FL (TRANSCEND FL; NCT04245839) and r/r B-cell non-Hodgkin lymphoma (B-NHL) (TRANSCEND NHL 001; NCT02631044), respectively.3 The company noted that in addition to meeting the ORR end point, both trials also met the CR rate end point and no new safety signals were observed in patients with FL and mantle cell lymphoma. Earlier this year, in January, Bristol Myers Squibb also announced that TRANSCEND CLL 004 (NCT03331198), a clinical trial which is evaluating liso-cel in patients with r/r chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, met a primary endpoint of "CR rate compared to historical control" in a prespecified subset of patients with CLL refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor.4
The new EC decision brings liso-cel's status in the EU into alignment with its status in the US, where it has been approved as a second-line treatment since last year: in June 2022, the therapy received FDA approval for the treatment of patients with LBCL whose disease was r/r to first-line treatment within 12 months and patients with LBCL whose disease was r/r to first-line treatment who are not eligible for hematopoietic stem cell transplant.5 The FDA approval was likewise based on results from TRANSFORM.
“With Breyanzi, 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, the senior vice president and head of Cell Therapy Development at Bristol Myers Squibb, added to the statement.1 “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.”