Yescarta Drug: A Breakthrough in Lymphoma Treatment

Yescarta Drug: A Breakthrough in Lymphoma Treatment

Yescarta (Axicabtagene ciloleucel, Axi-cel) has revolutionized the treatment landscape for lymphoma since its initial approval by the US FDA on October 18, 2017. As the world’s first chimeric antigen receptor T-cell (CAR-T) therapy for adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) who have received two or more lines of systemic therapy, Yescarta has ushered in a new era in lymphoma treatment.

Approval History and Indications

Yescarta received its first approval from the US FDA in 2017 for the treatment of adult patients with R/R LBCL after two or more lines of systemic therapy. Since then, it has gained approval in multiple countries worldwide, with expanded indications including:

1. United States (2017): R/R LBCL after two or more lines of systemic therapy

2. European Union (2018): R/R DLBCL and PMBCL after two or more lines of systemic therapy

3. Japan (2021): R/R LBCL after two or more lines of systemic therapy

4. China (2021): R/R LBCL after two or more lines of systemic therapy (marketed as 奕凯达® (Yikaida))

In 2022, Yescarta’s indications were expanded in several regions to include second-line treatment for certain LBCL patients.

Mechanism of Action

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy. It works by reprogramming a patient’s own T cells to target and eliminate CD19-expressing cancer cells.

Clinical Efficacy

The ZUMA-7 trial, a global multicenter phase III randomized controlled study, demonstrated significant improvement in overall survival (OS) for patients with primary refractory or early relapsed LBCL treated with Yescarta compared to standard of care (SOC) therapy. The study showed:

– 27% reduction in the risk of death with Yescarta

– Median OS not reached in the Yescarta group vs. 31.1 months in the SOC group

– 4-year OS rate of 54.6% for Yescarta vs. 46.0% for SOC

These results led to Yescarta receiving a Category 1 recommendation in the NCCN guidelines (2023.V6) for second-line treatment of primary refractory or relapsed within 12 months DLBCL patients.

Impact on Treatment Paradigm

Yescarta has significantly changed the treatment landscape for LBCL patients:

1. It offers a potentially curative option for patients who previously had limited treatment choices.

2. It has moved CAR-T therapy earlier in the treatment sequence, now being used as a second-line option for certain patients.

3. It has prompted updates to major treatment guidelines, including NCCN and CSCO.

Chinese Experience with 奕凯达® (Yikaida)

In China, Yescarta is marketed as 奕凯达® (Yikaida). It received approval from the National Medical Products Administration (NMPA) on June 23, 2021, for the treatment of adult patients with R/R LBCL after two or more lines of systemic therapy. On June 21, 2023, its second-line indication was also approved.

Real-world data from multiple 奕凯达® treatment centers in China have shown promising results, with interim analyses presented at major international conferences like EHA and ICML in 2023. These results represent the first large-sample, real-world data for commercial CAR-T treatment in Chinese R/R NHL patients.

Future Directions

While CAR-T therapy is currently used in relapsed/refractory settings, ongoing research is exploring its potential as a first-line treatment for high-risk LBCL patients. The ZUMA-12 study has shown rapid and durable high response rates with Axi-cel in first-line treatment of high-risk LBCL patients. The ongoing ZUMA-23 trial is comparing Axi-cel to SOC for first-line treatment of high-risk DLBCL.

Conclusion

Yescarta represents a significant breakthrough in lymphoma treatment, offering hope for cure to patients who previously had limited options. Its success has paved the way for further advancements in CAR-T therapy and has reshaped the treatment landscape for LBCL. As more clinical evidence accumulates and indications expand, Yescarta and its Chinese counterpart 奕凯达® are poised to benefit an increasing number of lymphoma patients worldwide, potentially moving towards first-line therapy for high-risk patients in the future.

The approval and implementation of Yescarta/奕凯达® mark the beginning of a new era in lymphoma treatment, bringing the possibility of cure closer to reality for many patients. As research continues and real-world experience grows, we can expect further refinements in the use of this groundbreaking therapy, potentially expanding its benefits to even more patients in need.