Yescarta 2L DLBCL

Yescarta 2L DLBCL

Diffuse large B-cell lymphoma (DLBCL) is one of the most common and aggressive types of non-Hodgkin’s lymphoma, affecting thousands of adults worldwide each year. Despite advances in chemotherapy and immunotherapy, a significant number of patients experience relapse or are refractory to first-line treatments. However, recent developments in CAR-T cell therapy have brought new hope to these patients. Yescarta®, a CAR-T cell therapy drug developed by Gilead Sciences’ Kite Pharma, has recently received FDA approval for second-line treatment of DLBCL, marking a significant milestone in the field of cancer treatment.

The Approval and Its Significance

On April 1, 2022, the U.S. Food and Drug Administration (FDA) approved Yescarta® for adult patients with DLBCL who are refractory to first-line chemoimmunotherapy or relapse within 12 months after such treatment. This approval is based on the results of the ZUMA-7 clinical trial, which demonstrated that Yescarta® significantly prolonged event-free survival (EFS) by 6.3 months compared to previous standard therapies. Additionally, the two-year survival rate without disease progression or the need for additional cancer treatment was 2.5 times higher with Yescarta® than with standard second-line therapy.

This approval marks Yescarta® as the world’s first CAR-T cell therapy drug to be approved by the FDA for second-line treatment of DLBCL. This breakthrough not only reflects the remarkable efficacy of Yescarta® but also signifies a paradigm shift in the treatment of hematological malignancies.

Efficacy and Safety Profile

The ZUMA-7 trial, a randomized, open-label, global, multicenter phase 3 study, compared the safety and efficacy of Yescarta® with standard second-line therapy in adult patients with relapsed or refractory DLBCL within 12 months after first-line treatment. The study enrolled 359 patients from 77 centers worldwide, who were randomly assigned to receive a single infusion of Yescarta® or standard second-line therapy.

The results showed that Yescarta® treatment had a statistically significant clinical advantage, with an improvement in EFS more than four times that of standard second-line therapy (8.3 months vs. 2.0 months). Furthermore, the two-year survival rate without disease progression or the need for additional cancer treatment was 40.5% with Yescarta® compared to 16.3% with standard second-line therapy, indicating a 2.5-fold increase. Importantly, the safety profile of Yescarta® was manageable, with no unexpected adverse events reported.

The Potential of Yescarta® as a New Standard of Care

Given its outstanding efficacy and manageable safety profile, Yescarta® has the potential to become the new standard of care for patients with relapsed or refractory DLBCL. Professor Ma Jun, Director of Harbin Institute of Hematology and Oncology and Vice-Chairman of the Asian Clinical Oncology Society, stated, “Yescarta® has shown remarkable efficacy superior to the standard therapy for relapsed or refractory DLBCL patients over the past thirty years, fundamentally changing our understanding of the treatment of hematological malignancies.”

Furthermore, in March 2022, the National Comprehensive Cancer Network (NCCN) included Yescarta® as a category 1 recommendation for the treatment of DLBCL with “disease relapse within 12 months or primary refractory disease.” This makes Yescarta® the first CAR-T cell drug to be recommended as category 1 by the NCCN for any type of cancer treatment.

The Impact on Patient Care and Treatment Patterns

The approval of Yescarta® for second-line treatment of DLBCL represents a significant change in patient care and treatment patterns. Unlike traditional multi-step treatments, patients receiving Yescarta® only need a single infusion, significantly reducing the treatment burden and improving their quality of life.

Dr. Huang Hai, CEO of Fosun Kite, expressed optimism about bringing this innovative therapy to more Chinese patients, stating, “The FDA approval of Yescarta® for second-line treatment of DLBCL is a milestone that brings hope to more lymphoma patients. Fosun Kite will promptly carry out registration work for second-line treatment of DLBCL in China, looking forward to bringing this innovative therapy to more Chinese patients as soon as possible.”

Future Perspectives and Challenges

While the approval of Yescarta® represents a significant advancement in the treatment of DLBCL, there are still challenges to be addressed. The high cost of CAR-T cell therapy remains a barrier to its widespread adoption. Additionally, further research is needed to identify patients who are most likely to benefit from Yescarta® and to optimize its use in combination with other therapies.

Conclusion

Yescarta® has emerged as a game-changer in the treatment of relapsed or refractory DLBCL, offering patients a new hope for durable remission and improved quality of life. Its approval as a second-line therapy by the FDA marks a significant milestone in the field of cancer treatment and paves the way for further advancements in CAR-T cell therapy. As we continue to explore the potential of this innovative treatment, we can expect more breakthroughs that will ultimately lead to better outcomes for patients with DLBCL and other hematological malignancies.