Data-informed optimization of CAR T-cell therapy long-term follow-up

Area of Science:

• Oncology
• Immunotherapy
• Clinical Research

Background:

• Current long-term follow-up (LTFU) requirements for chimeric antigen receptor (CAR) T-cell therapy are extensive, posing challenges.
• A 15-year LTFU period is standard but its scientific justification is questioned.

Purpose of the Study:

• To reassess the scientific justification for a 15-year LTFU period for CAR T-cell therapy.
• To evaluate the current cumulative safety data for CAR T-cell therapies.
• To propose a streamlined data collection process and regulatory considerations.

Main Methods:

• Convened a multistakeholder working group (patients, academia, industry, government).
• Aggregated primary data on adverse events (AEs) for five FDA-approved CAR T-cell therapies.
• Analyzed AEs by year post-infusion, including secondary T-cell malignancies.

Main Results:

• Adverse events (AEs) are infrequently reported after 3 years post-infusion.
• Secondary T-cell malignancies, a key concern, were predominantly reported within the first 2 years.
• Current cumulative safety data suggest a 5-year follow-up may be sufficient.

Conclusions:

• A 5-year follow-up period may be scientifically sufficient for CAR T-cell therapy in clinical trials and commercial settings.
• A streamlined, technology-leveraged data collection process is proposed.
• Feasibility testing and regulatory policy adjustments are recommended for adoption.