CAR T: HOPE FOR CANCER PATIENTS WORLDWIDE

CAR-T cell therapy has emerged as a transformative treatment for relapsed/refractory large B-cell lymphoma (LBCL), offering durable remissions where traditional therapies often fail.
This genetically engineered immunotherapy reprograms a patient's T-cells to target CD19-positive B-cells, with three FDA-approved therapies demonstrating efficacy in clinical trials.

Approved CAR-T Therapies for LBCL

  • Axicabtagene ciloleucel (Yescarta): Achieved 40% 4-year survival in ZUMA-1 trial
  • Lisocabtagene maraleucel (Breyanzi): Showed 74% complete response rate in TRANSFORM trial
  • Tisagenlecleucel (Kymriah): Demonstrated 40% ongoing remission at 24 months in JULIET trial

Treatment Process

  1. Leukapheresis: T-cell collection (3-4 hour procedure)
  2. Genetic Engineering: 2-4 week manufacturing period to add CD19-targeting CAR receptors
  3. Lymphodepletion: Cyclophosphamide/fludarabine chemotherapy to prepare the immune system
  4. Infusion: Single-dose administration followed by 30-day monitoring for toxicities

Key Clinical Trial Outcomes

Trial Therapy Key Result
ZUMA-7 Axi-cel 40.5% 2-year EFS vs 16.3% with ASCT
TRANSFORM Liso-cel 74% CR vs 43% with salvage+ASCT
BELINDA Tisa-cel No significant EFS improvement

Toxicity Management

  • Cytokine Release Syndrome (CRS): Managed with tocilizumab (IL-6 inhibitor)
  • ICANS Neurotoxicity: 15-30% incidence across products, typically reversible
  • Late Effects: 30% risk of prolonged cytopenias, 10% hypogammaglobulinemia

Recent phase 3 trials support CAR-T as second-line therapy for patients refractory to first-line treatment or relapsing within 12 months. The TRANSFORM trial demonstrated liso-cel's superiority over salvage chemotherapy+ASCT, with median EFS not reached vs 2.4 months. Real-world data shows 35-40% of patients achieving 5-year remission.

While CAR-T presents logistical challenges, it has redefined treatment paradigms by providing curative potential where conventional approaches failed. Ongoing research focuses on optimizing manufacturing, reducing toxicity, and expanding access to earlier lines of therapy.


Sources:
ashpublications.org
targetedonc.com
WebMD
lymphoma.org
Pubmed
pmc.ncbi.nlm.nih.gov
Oncive
nature.com

Publication date: March 2025