Bendamustine Before CAR T-cell Therapy Shows Lower Side Effects While Maintaining Efficacy

New research presented at the 2024 American Society of Hematology (ASH) Annual Meeting reveals an alternative pre-treatment option that could make CAR T-cell therapy safer for patients with aggressive lymphomas while maintaining its effectiveness.

The study, presented by Dr. Alaa Ali from Georgetown University's Lombardi Comprehensive Cancer Center, represents a nationwide collaboration led by the Medical College of Wisconsin. This extensive research effort, involving multiple centers across the United States, including Texas, Kansas, Ohio, and Iowa, analyzed data from over 5,000 patients who received CAR T-cell therapy for large B-cell lymphoma. The findings show that using bendamustine instead of the standard fludarabine for lymphodepletion resulted in fewer severe side effects without compromising long-term survival.

Watch Dr. Alaa Ali explain what lymphodepletion is and its role in CAR T-cell therapy and summarize the study's key results.

Why This Is Important for You

Before receiving CAR T-cell therapy, patients need lymphodepletion – a process that creates space for the engineered T-cells to work effectively. While fludarabine has been the standard choice, some patients experience significant side effects, and recent shortages have prompted the search for alternatives.

Key Findings:

• Fewer side effects: patients receiving bendamustine experienced:

• Lower rates of severe cytokine release syndrome (4.5% vs 7.7%)

• Reduced severe neurological effects (8.3% vs 16.7%)

• Less prolonged low blood counts (11.6% vs 20%)

• Using a different lymphodepletion regimen didn’t impact CAR T-cell therapy effectiveness:

• Similar overall survival rates at one year (around 61%)

• Comparable progression-free survival

• Slightly lower initial response rates, though this didn't affect long-term outcomes

"These findings are particularly relevant for patients who might be more vulnerable to side effects," explains Dr. Ali. "While the standard fludarabine-based approach remains effective, having a safer alternative opens up possibilities for personalizing treatment based on individual patient needs."

Who Might Benefit Most?

This alternative approach could be particularly valuable for:

• Older patients

• Those with other health conditions

• Patients more susceptible to treatment side effects

• Situations where fludarabine isn't available or suitable

Looking Ahead

While longer follow-up is needed to confirm these results, the study suggests that doctors can now consider bendamustine as a viable alternative for lymphodepletion, especially for patients at higher risk of complications.

The research included patients treated with all commercially available CAR T-cell products (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel), making the findings broadly applicable.

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Source:

• Real-World Comparison of Efficacy and Safety of Fludarabine-Versus Bendamustine-Based Lymphodepleting Chemotherapy for CD19 Chimeric Antigen Receptor (CAR) T-Cell Therapy in Relapse/Refractory (r/r) Large B-Cell Lymphoma (LBCL)