Axicabtagene ciloleucel significantly improved event-free survival by 60% over chemotherapy plus stem cell transplant in the second-line treatment of patients with relapsed or refractory large B-cell lymphoma, meeting the primary end point of the phase 3 ZUMA-7 trial.
Axicabtagene ciloleucel (axi-cel; Yescarta) significantly improved event-free survival (EFS) by 60% over chemotherapy plus stem cell transplant in the second-line treatment of patients with relapsed or refractory large B-cell lymphoma (LBCL), meeting the primary end point of the phase 3 ZUMA-7 trial (NCT03391466).1
At a median follow-up of 2 years, the longest follow-up time of any study done in this setting, the effort met the primary end point of EFS (HR, 0.398; P <.0001), as well as the secondary end point of objective response rate. Moreover, data from the interim analysis for overall survival (OS) revealed a trend that favored the CAR T-cell therapy, although the findings remain immature. Additional analyses for the trial are planned.
Safety findings proved to be consistent with, or lower than, what has previously been seen with axi-cel in the treatment of patients with LBCL in the third-line treatment setting. In this study, 6% of participants reported cytokine release syndrome that was grade 3 or higher in severity, with a median onset of 3 days. Moreover, 21% of patients experienced grade 3 or higher neurological effects. Notably, no new safety signals were observed with the use of the CAR T-cell product in the second-line setting.
Detailed data from the trial have been submitted for presentation at a future medical meeting. Additionally, the pharmaceutical company shared plans to start discussions with the FDA, the European Medicines Agency, and other global health authorities pertaining to a potential supplemental biologics license application submission later in 2021 to expand the currently approved indications for the CAR T-cell product.
“[Axi-cel] has been instrumental in transforming outcomes for patients with third-line LBCL. Our goal has always been to bring the benefit of CAR T-cell therapy to more patients, earlier in their treatment, where the potential for benefit may be even greater,” Christi Shaw, chief executive officer of Kite Pharma, stated in a press release. “As the leader in cell therapy, Kite is honored to deliver this landmark study and would like to thank the patients, families, physicians, and care teams around the world that made this possible.”
In the open-label, global, multicenter phase 3 ZUMA-7 trial, investigators examined the safety and efficacy of axi-cel vs current standard of care (SOC), which is a platinum-based salvage combination chemotherapy regimen followed by high-dose therapy and autologous stem cell transplant in those who respond to salvage chemotherapy, for the second-line treatment of patients with relapsed or refractory LBCL.2
Patients needed to have histologically proven LBCL, including those with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high-grade B-cell lymphoma with MYC and BLC2 or BCL6 rearrangement, DLBCL arising from follicular lymphoma, T-cell/histiocyte rich LBCL, DLBCL linked with chronic inflammation, primary cutaneous DLBCL, and Epstein-Barr virus plus DLBCL. Other inclusion criteria included relapsed or refractory disease following frontline chemoimmunotherapy; receiving acceptable frontline therapy, including an anti-CD20 monoclonal antibody and an anthracycline-containing chemotherapy regimen; an ECOG performance status of 0 or 1; acceptable bone marrow function; and adequate renal, hepatic, cardiac, and pulmonary function.
Patients could not have a known history or suspicion of central nervous system involvement by lymphoma. Moreover, patients could not have a history of malignancy other than nonmelanoma skin cancer or carcinoma in situ, could not have received more than 1 line of therapy for DLBCL, and have a history of autologous or allogeneic stem cell transplant, among others.
A total of 359 patients were enrolled to ZUMA-7, which was initiated in 2017. Study participants were randomized 1:1 to receive a single infusion of the CAR T-cell product or SOC as second-line treatment. Patients ranged in age from 22 years to 81 years; 30% of patients were aged 65 years or older.
Those who were randomized to axi-cel undergo leukapheresis, followed by lymphodepletion chemotherapy, which is comprised of fludarabine at a daily dose of 30 mg/m2 and cyclophosphamide at a daily dose of 500 mg/m2 for 3 days.3 This is followed by a single infusion of the CAR T-cell product at a dose of 2 x 106 CAR T cells/kg. Investigators permitted the use of corticosteroid bridging therapy for patients who had a high disease burden at the time of screening.
The primary end point of the study was EFS, and key secondary end points include modified EFS, progression-free survival, and duration of response.
“Over 40 years ago, we learned the important role T cells play in fighting cancer, and 20 years ago, autologous stem cell transplant became an option to treat lymphoma,” Frank Neumann, MD, PhD, global head of clinical development at Kite Pharma, added in the release. “Today’s results show the potential power of cell therapy for patients with lymphoma when used earlier, and instead of standard treatment options.”