What if CAR T-cell therapy fails?

When CAR T-cell therapy fails in treating blood cancers, patients and oncologists face a challenging situation with limited treatment options. However, several strategies can be considered:

Second CAR T-Cell Infusion

A second infusion of CAR T cells has shown promise for some patients:

Response rates: Studies report a 39% overall response rate after a second infusion, with 20% achieving complete responses.
Durability: Median response durations varied by disease type, ranging from 4 months in acute lymphoblastic leukemia (ALL) to 33 months in chronic lymphocytic leukemia (CLL).
Toxicity: Second infusions typically cause milder side effects, with severe cytokine release syndrome (9%) and neurotoxicity (11%) being rare.

Factors associated with better outcomes after a second infusion include:

Increased cell dose for the second infusion
Use of cyclophosphamide plus fludarabine (Cy-Flu) lymphodepletion before the first infusion
Disease type (non-Hodgkin lymphoma and CLL patients generally fare better than ALL patients)

Alternative Treatments

If a second CAR T-cell infusion is not viable, other options include:

Bispecific antibodies: These drugs act as "molecular bridges" between T cells and cancer cells, showing efficacy in post-CAR T relapses.
Combination therapies: Immunomodulators or antibody-drug conjugates may enhance treatment effectiveness.
Traditional therapies: Chemotherapy, radiation, or targeted therapies remain options for some patients.