YESCARTA (axicabtagene ciloleucel) is a CD19-directed genetically modified autologous T-cell immunotherapy. YESCARTA, a patient’s T cells are harvested and genetically modified ex vivo by retroviral transduction to express a chimeric antigen receptor (CAR) comprising a murine anti-CD19 single-chain variable fragment (scFv) linked to CD28 and CD3-zeta costimulatory domains. The antiCD19 CAR-T cells are expanded and infused back into the patient, where they can recognize and eliminate CD19-expressing target cells. Based on the results of primary efficacy endpoint of event-free survival (EFS) in the pivotal ZUMA-7 trial, the US FDA approved YESCARTA as initial treatment of R/R LBCL in April 2022. The EU granted approval in October 2022, followed by approvals in several other countries such as: Australia, Canada, Great Britain, Israel, Japan and Switzerland. According to the results presented at the ASCO 2023, around 359 patients underwent randomization to receive axi-cel (180 patients) or standard care (179 patients). At a median follow-up of 47.2 months, death had been reported in 82 patients in the axicabtagene ciloleucel group and in 95 patients in the standard-care group. Apart from that, the median overall survival was not reached in the axicabtagene ciloleucel group and was 31.1 months in the standard-care group; the estimated 4-year overall survival was 54.6% and 46.0%, respectively.
In the axicabtagene ciloleucel group, the median progression-free survival, as assessed by the investigators, reached 14.7 months, a substantial improvement compared to the standard-care group, which achieved a median of only 3.7 months. Impressively, the estimated 4-year percentages further reinforced the effectiveness of axicabtagene ciloleucel, with a remarkable 41.8% compared to 24.4% in the standard-care group.
Axicabtagene ciloleucel emerged as a game-changer in the second-line treatment for early relapsed or refractory LBCL, demonstrating a remarkable enhancement in overall survival (OS) when compared to high-dose therapy plus autologous stem cell transplant (HDT/ASCT). Remarkably, the treatment yielded a significant 27.4% decrease in the risk of mortality, underscoring its potential as a transformative approach in patient care.
YESCARTA continued to demonstrate a consistent safety profile in line with previous studies, with no new treatment-related deaths reported since the primary analysis of event-free survival (EFS). The primary EFS analysis revealed that Grade 3 or higher adverse events (AEs) occurred in 91% of patients receiving axicabtagene ciloleucel, compared to 83% of those receiving standard of care (SOC). Neutropenia emerged as the most prevalent grade 3 or higher AE, observed in 69% of axicabtagene ciloleucel patients versus 41% in the SOC group. Additionally, anemia (30% vs. 39%) and leukopenia (29% vs. 22%) were notable grade 3 or higher AEs observed in the respective treatment groups.
KOL insights
“ZUMA-7 confirms axi-cel is a second-line standard of care for patients with refractory or early relapsed large B-cell lymphoma based on superior survival.” –Expert Opinion.
“Overall survival is the gold standard in cancer treatment and confirms YESCARTA’S place as a treatment of curative intent for patients with relapsed/refractory large B-cell lymphoma.” –Expert Opinion.
Conclusion
The groundbreaking results from the ZUMA-7 trial demonstrated that patients experience significantly improved overall survival when treated with axicabtagene ciloleucel in the second-line setting, surpassing the outcomes achieved with chemotherapy and stem cell transplant. This pivotal finding underscores the transformative potential of axicabtagene ciloleucel in reshaping the treatment landscape and offering renewed hope for patients in need of advanced therapies
