How Does Axi-cel Perform in the Real World for People with LBCL?

Clinical trials carefully screen candidates based on strict inclusion and exclusion criteria. However, in real-world settings, many patients do not meet all the trial criteria, which may lead to different outcomes than those reported in controlled studies. 

This raises an important question: Does the CAR T-cell therapy axi-cel impact large B-cell lymphoma (LBCL) patients differently in real-world practice compared to people in the clinical trial that led to its FDA approval? 

Axi-cel in the ZUMA-7 Trial vs. Real-World for LBCL 

To better understand the real-world effects of axi-cel (Yescarta, Kite), several LBCL specialists analyzed medical records from 446 patients with relapsed/refractory LBCL who received axi-cel as a second-line treatment in the U.S. between April 2022 and July 2023. The findings were presented at the 2024 ASH conference. 

Notably, about half of these patients would not have qualified for the ZUMA-7 clinical trial, primarily due to not meeting the trial’s inclusion criteria.

Despite these differences, treatment response rates remained positive. After receiving axi-cel, 79% of patients experienced a reduction in cancer cells, with 64% achieving complete remission. At the 12-month follow-up, 66% of people who achieved remission sustained it, and 71% of all patients were alive.

When researchers compared outcomes between patients who met ZUMA-7 criteria and those who did not, they found that results at 12 months were similar across both groups. This suggests that axi-cel remains effective in a broader patient population beyond the controlled trial setting.

Reviewing Axi-cel’s Side Effects Over the Years

In addition to effectiveness, researchers also examined how the management of axi-cel-related side effects has evolved. A study led by Jiasheng Wang, MD, focused on two common toxicities associated with CAR T-cell therapy:

• Cytokine release syndrome (CRS)
• Immune effector cell-associated neurotoxicity syndrome (ICANS)

The study analyzed 1,615 LBCL patients who received axi-cel as a third or later line of therapy between 2017 and 2023, dividing them into three groups based on the treatment years: 2017–2019, 2020–2021, and 2022–2023. 

The goal was to evaluate whether advancements in side effect management—such as the earlier use of corticosteroids and tocilizumab, along with more experienced care teams—improved patient outcomes. 

Key findings included:

• Patients treated in 2022–2023 and 2020–2021 had significantly lower rates of severe CRS (grade ≥3) compared to those treated in 2017–2019
• CRS episodes in more recent years were shorter in duration than those in 2017–2019
• The incidence of any type of ICANS (mild to severe) was notably lower in 2022–2023 and 2020–2021 than in earlier years
• The duration of ICANS in 2020–2021 was significantly shorter compared to 2017–2019

Over the years, researchers observed an increase in additional clinical practices alongside the earlier use of corticosteroids and tocilizumab. More patients received bridging therapy while preparing for CAR T-cell treatment, and the use of anakinra, an anti-inflammatory medication, also grew to help manage CRS and ICANS. 

These findings suggest that improved management strategies have enhanced patient safety over time, reducing the severity and duration of these side effects. 

Conclusion

Real-world evidence supports the effectiveness of axi-cel for LBCL, even in patients who would not have met the ZUMA-7 trial criteria. Outcomes at 12 months post-treatment closely mirrored those seen in the clinical trial, reinforcing axi-cel’s role as a valuable therapy for relapsed/refractory LBCL. 

Furthermore, advancements in managing CRS and ICANS over the years have led to better safety outcomes, with fewer and shorter-lasting side effects for patients receiving axi-cel more recently. These insights highlight the importance of ongoing real-world research. 

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Sources: 

• Real-World Early Outcomes of Second-Line Axicabtagene Ciloleucel (Axi-Cel) Therapy in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
• Real-World Trends of Cytokine Release Syndrome and Neurologic Events, and Pattern of Their Management Among Patients Receiving Axicabtagene Ciloleucel for Relapsed or Refractory (r/r) Large B-Cell Lymphoma (LBCL) in the US: A CIBMTR Report
• 906. Outcomes Research: Lymphoid Malignancies Excluding Plasma Cell Disorders: CAR-T Cell Therapy in Action: Real-World Outcomes in Lymphoma