The European Commission has approved Breyanzi ( Lisocabtagene maraleucel; Liso-cel ) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma ( DLBCL ), primary mediastinal large B-cell lymphoma ( PMBCL ), and follicular lymphoma grade 3B ( FL3B ) following 2 or more lines of systemic therapy.

The approval is based on findings from the phase 1 TRANSCEND NHL 001 trial, and additional data from the phase 2 TRANSCEND WORLD trial.

The open-label, multicenter, phase 1 TRANSCEND NHL 001 trial enrolled patients with relapsed / refractory large B-cell lymphoma, including DLBCL, high-grade B-cell lymphoma, PMBCL, and FL3B, who were at least 18 years of age, had an ECOG performance status ranging from 0 to 2, a creatinine clearance level of 30 mL/min/1.73 m2, and a left ventricular ejection fraction of at least 40%.

Patients who previously underwent hematopoietic stem cell transplantation were permitted, as well as those with secondary central nervous system ( CNS ) lymphoma.

After screening, patients underwent leukapheresis. Bridging therapy was permitted during the manufacturing of the CAR T-cell product.
After PET-positive disease was reconfirmed, patients received a lymphodepletion regimen comprised of Fludarabine at 30 mg/m2 and Cytarabine at a dose of 300 mg/m2 for 3 days.
Patients then received Liso-cel at 1 of the following 3 dose levels 2 to 7 days after lymphodepletion: 50 x 10(6) CAR-positive T cells ( dose level 1 ), 100 x 10(6) CAR-positive T cells ( dose level 2 ), and 150 x 10(6) CAR-positive T cells ( dose level 3 ).

The primary end points of the trial were adverse effects and objective response rate ( ORR ) per independent review committee ( IRC ).
Key secondary end points have included complete response ( CR ) rate by IRC, duration of response ( DoR ), progression-free survival ( PFS ), overall survival ( OS ), and pharmacokinetics.

Data from a prior analysis of the trial have shown that the CAR T-cell therapy elicited an ORR of 73%, with a CR rate of 53%.
Two-year follow-up findings from the trial were presented during the 2021 ASH Annual Meeting. The overall median follow-up was 19.9 months ( range, 0.2-45.2 ).

The median age among the 270 patients who received treatment with Liso-cel was 63 years ( range, 18-86 ), with 41% of patients 65 years of age or older and 10% who were 75 years of age or older.
Moreover, 99% of patients had an ECOG performance status of 0, 3% had secondary CNS lymphoma, 67% were refractory to chemotherapy, and 44% had never achieved a complete response.
The median number of prior lines of systemic therapy received was 3 ( range, 1-8 ), 33% received prior autologous transplant, 3% had prior allogeneic transplant, and 59% received bridging therapy.

Data have shown that the median DoR was 23.1 months ( 95% CI, 8.6–not reached ), and the probability of continued response at 2 years was 49.5% ( 95% CI, 41.4-57.0% ).
The median PFS per IRC was 6.8 months ( 95% CI, 3.3-12.7 ), and the probability of PFS at 2 years was 40.6% ( 95% CI, 34.0-47.2% ).
The median OS was 27.3 months ( 95% CI, 16.2-45.6 ), and the probability of OS at 2 years was 50.5% ( 95% CI, 44.1-56.5% ).

Within 90 days of Liso-cel infusion, 99% of patients experienced any-grade toxicities and 79% experienced grade 3 or higher toxicities.
Seventy-four percent of patients experienced any-grade adverse effects associated with Liso-cel, and 35% experienced Liso-cel–related adverse effects that were grade 3 or higher.

The most common grade 3 or higher toxicities included neutropenia ( 60% ), anemia ( 37% ), thrombocytopenia ( 27% ), decreased appetite ( 3% ), hypotension ( 3% ), cytokine release syndrome ( 2% ), fatigue ( 1% ), nausea ( 1% ), headache ( 1% ), diarrhea ( less than 1% ), dizziness ( less than 1% ), and vomiting ( less than 1% ). ( Xagena )

Source: BMS, 2022

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