CAR T-cell therapy can be administered twice for blood cancers, and this approach has shown promise for some patients who fail to respond or relapse after the initial treatment. Here are key points about second CAR T-cell infusions:
Efficacy
- Overall response rate: Studies report a 39% overall response rate after a second infusion, with 20% of patients achieving complete responses.
- Response duration: Median durations of response varied by disease type, ranging from 4 months in acute lymphoblastic leukemia (ALL) to 33 months in chronic lymphocytic leukemia (CLL).
- Disease-specific outcomes: Complete response rates after second infusion were 22% for CLL, 19% for non-Hodgkin lymphoma (NHL), and 21% for ALL.
#CART25 - European hematology conference in Strasbourg, France.
Safety
- Lower toxicity: Second infusions typically cause milder side effects compared to the first treatment.
- Cytokine release syndrome (CRS): Severe CRS (grade ≥3) occurred in only 9% of patients receiving a second infusion.
- Neurotoxicity: Severe neurotoxicity (grade ≥3) was observed in 11% of patients after the second infusion.
Factors influencing success
- Increased cell dose: Higher CAR T-cell doses in the second infusion correlated with better outcomes.
- Lymphodepletion regimen: Patients who received cyclophosphamide plus fludarabine (Cy-Flu) before the first infusion had improved CAR T-cell persistence and response rates after the second dose.
- Disease type: NHL and CLL patients generally fared better than ALL patients.
While second CAR T-cell infusions have shown potential, it's important to note that long-term survival remains unknown. Ongoing research continues to explore strategies for improving outcomes after CAR T-cell therapy failure, including novel CAR designs and combination approaches.
Publication date: March 2025
Sources
ashpublications.org
pmc.ncbi.nlm.nih.gov
pubmed.ncbi.nlm.nih.gov
targetedonc.com
bloodcancerstoday.com
cancer.gov
ashpublications.org
acgtfoundation.org
