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Lisocabtagene maraleucel demonstrated a highly significant improvement in event-free survival, complete response rate, and progression-free survival over standard of care in the second-line treatment of patients with relapsed/refractory large B-cell lymphoma, meeting primary and secondary end points of the phase 3 TRANSFORM trial.
Lisocabtagene maraleucel (liso-cel; Breyanzi) demonstrated a highly significant improvement in event-free survival (EFS), complete response (CR) rate, and progression-free survival (PFS) over standard of care (SOC) in the second-line treatment of patients with relapsed/refractory large B-cell lymphoma (LBCL), meeting primary and secondary end points of the phase 3 TRANSFORM trial (NCT03575351).1
These data signify the first time a therapy has demonstrated benefit over the gold standard of high-dose chemotherapy and hematopoietic stem cell transplant (HSCT) in this patient population, according to Bristol Myers Squibb. Moreover, this is also the first time a CD19-directed CAR T-cell therapy showcased potential for use as a second-line option in these patients.
The overall survival data remain immature at this time point, but safety findings have proven to be consistent with the known toxicity profile of the CAR T-cell product as a third-line treatment approach for patients with LBCL. No new signals were observed with the agent in the second-line setting.
“We ambitiously designed the TRANSFORM trial to evaluate [liso-cel’s] potential in the second-line setting for patients with relapsed or refractory LBCL against the SOC regimen of high-dose chemotherapy and autologous stem cell transplant,” Noah Berkowitz, MD, PhD, senior vice president of Hematology and Cell Therapy Development at Bristol Myers Squibb, stated in a press release. “These positive interim results build on our commitment to bring CAR T-cell therapies into earlier lines and highlight the potential of [liso-cel] to transform the treatment paradigm for this difficult-to-treat disease, possibly supplanting the need for patients to undergo current aggressive treatment regimens.”
In the global, multicenter phase 3 trial, investigators compared the safety and efficacy of liso-cel with current SOC regimens, which included high-dose chemotherapy and HSCT in adult patients with LBCL that was either primary refractory or had relapsed within 1 year of initial treatment. Patients had to be candidates for stem cell transplant.2
To be eligible for enrollment, patients needed to be between the ages of 18 years and 75 years, have an ECOG performance status of 0 or 1, have an 18F-fluorodeoxyglucose positron emission tomography positive lesion at screening, and acceptable organ function.
Those planned to undergo allogeneic stem cell transplant or who were not eligible for HSCT were excluded, as were those with a prior history of malignancies beyond aggressive relapsed/refractory non-Hodgkin lymphoma and those who had previously received a gene therapy or CD19-targeted treatment.
Study participants were randomized to receive either liso-cel or investigator’s choice of SOC salvage therapy, which could include rituximab (Rituxan) plus dexamethasone, high-dose cytarabine, and cisplatin; rituximab plus ifosfamide, carboplatin, and etoposide; or rituximab plus gemcitabine, dexamethasone, and cisplatin. Patients then proceeded to high-dose chemotherapy and HSCT.
The primary end point of the trial was EFS, which was defined as the time from randomization to death from any cause, progressive disease, failure to experience a CR or partial response by 9 weeks following randomization or start of new antineoplastic therapy because of efficacy concerns—whichever occurred first. CR rate served as a key secondary end point. Other efficacy end points included PFS, overall survival, overall response rate, and duration of response.
Notably, all patients who enrolled to the trial had LBCL that was relapsed or refractory within 1 year of receipt of a CD20 antibody– and anthracycline-containing frontline therapy.
In February 2021, the FDA approved liso-cel for the treatment of adult patients with certain types of LBCL who have not responded to, or who have relapsed after, at least 2 other types of systemic treatment.3
Data from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) showed that the CAR T-cell product elicited in ORR of 73% (95% CI, 66.8%-78.0%) with a CR rate of 53% (95% CI, 46.8%-59.8%) in this patient population; these findings supported the approval of the product.4,5