Breyanzi Receives FDA Approval for Second-Line Treatment of Large B-Cell Lymphoma

On 24 June 2022, the FDA (United States Food and Drug Administration) approved treatment for adults whose disease was refractory to first-line chemoimmunotherapy or relapsed within 12 months and who, because of comorbidities or age, were not suitable for a stem cell transplant and who had large B-cell lymphoma (BBHL). The approved CAR T-cell therapy is lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.). This approval does not include treatment of patients with central nervous system lymphoma. Previously, Yescarta had also received FDA approval to treat patients in this situation.

Breyanzi had previously received FDA approval on 5 February 2021 to treat adult patients with types of diffuse large B-cell lymphoma that had not responded to or had relapsed after "at least two prior lines of treatment" (see the related approval and the mechanism of action of this CAR T-cell therapy). 

Breyanzi is the 3rd CAR T-cell therapy approved by the FDA.

Two Studies Leading to FDA Approval for Second-Line CAR T-Cell Therapy

The TRANSFORM Study

Efficacy was assessed in TRANSFORM, a randomized, open-label, multicenter study in adults with BBHL refractory to first-line chemoimmunotherapy or whose cancer relapsed within 12 months after achieving a complete response (TY) to first-line treatment.

Patients had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous stem cell transplantation. A total of 184 patients were randomized 1:1 to receive a single lisocabtagene maraleucel infusion following fludarabine and cyclophosphamide lymphodepleting chemotherapy, or second-line standard treatment consisting of three cycles of chemoimmunotherapy followed, in those achieving TY or a partial response (KY), by high-dose therapy and autologous stem cell transplantation.

The primary efficacy measure was event-free survival as determined by an independent review committee.

CAR T-cell therapy reduced the risk of any disease-related event by 66% (HR 0.34 and 95% CI: 0.22, 0.52; p-value <0.0001).

Estimated 1-year event-free survival was 45% (95% CI: 29, 59) in the lisocabtagene maraleucel arm and 24% (95% CI: 14, 35) in the standard-treatment arm.

Estimated median event-free survival was 10.1 months (95% CI: 6.1, not evaluable) and 2.3 months (95% CI: 2.2, 4.3), respectively.

Of patients randomized to standard treatment, 47% underwent autologous stem cell transplantation as planned, and lack of response to chemotherapy was the most common reason transplantation could not be performed.

The PILOT Study

Efficacy was also assessed in PILOT, a single-arm, open-label, multicenter trial in transplant-ineligible patients with BBHL that had relapsed or was refractory after one line of chemoimmunotherapy. It enrolled patients ineligible for high-dose chemotherapy and stem cell transplantation because of organ function or age, but with sufficient organ function for CAR T-cell therapy.

Efficacy was based on complete response (TY) rate and duration of response.

Of the 74 patients who underwent leukapheresis (median age, 73 years), 61 (82%) received lisocabtagene maraleucel, and 54% of them (95% CI: 41, 67) achieved TY. Median duration of response in patients achieving TY (95% CI: 11.2 months, not reached).

Side Effects

In studies of lisocabtagene maraleucel as second-line treatment for BBHL, cytokine release syndrome occurred in 45% of patients (grade 3 or higher, 1.3%), and neurological toxicities occurred in 27% (grade 3, 7%). Serious adverse reactions occurred in 33% to 38% of patients.

Dose

The recommended lisocabtagene maraleucel dose for second-line treatment is 90 million to 110 million CAR-positive T cells with CD4 and CD8 components in a 1:1 ratio.