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Anti-CD19 CAR-T Therapy Superior to Standard of Care as Second-Line Treatment for DLBCL
Axicabtagene ciloleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell treatment, offered a statistically significant clinical improvement over standard of care therapy for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) according to results from the ZUMA-7 phase 3 trial.
The current standard of care is second-line chemoimmunotherapy with autologous stem cell rescue (HDT-ASCT).
Many patients do not respond or cannot tolerate chemoimmunotherapy. Additionally, HDT-ASCT is not intended for this patient population, thus outcomes remain poor.
In the ZUMA-7 trial, a total of 359 patients were enrolled worldwide. Overall, 74% of patients had primary refractory disease. Patients were either randomized to standard of care therapy or axicabtagene ciloleucel.
In the standard of care arm, patients received 2 to 3 cycles of an investigator-selected, protocol defined, platinum-based CIT regimen, and those with partial response or complete response (CR) proceeded to HDT-ASCT.
In the axicabtagene ciloleucel arm, patients received a single infusion of 2×106 CAR T cells/kg after conditioning (cyclophosphamide 500 mg/m2/day and fludarabine 30 mg/m2/day). Optional bridging treatment was limited to corticosteroids.
The primary endpoint was event-free survival (EFS) by blinded central review, which was met (HR: 0.398; P<.0001).
Further, at a 24.9 month median follow-up, median EFS was significantly longer with axicabtagene ciloleucel vs standard of care (8.3 months [95% CI: 4.5–15.8] vs 2 months [95% CI: 1.6–2.8], respectively). Among randomized patients, overall response rate (ORR) and CR rates were higher with axicabtagene ciloleucel vs standard of care (ORR, 83% vs 50%, CR: 65% vs 32%).
“Axicabtagene ciloleucel showed superiority over SOC with more than 4-fold greater median EFS, 2.5-fold greater EFS at 2 years, double the CR rate, and more than double the percentage of patients receiving definitive treatment. Safety of axicabtagene ciloleucel was manageable and at least consistent with third-line therapy. the axicabtagene ciloleucel may replace CIT or HDT-ASCT as the standard of care for second-line R/R LBCL,” wrote lead author Frederick L. Locke, MD, Moffitt Cancer Center, Tampa, and co-authors.
