Is adoptive lymphocyte (CAR‑T) therapy appropriate for my patient with relapsed B‑cell lymphoma after multiple prior treatments?

CAR-T Therapy for Relapsed B-Cell Lymphoma After Multiple Prior Treatments

Yes, CAR-T cell therapy (axicabtagene ciloleucel or tisagenlecleucel) is appropriate for your patient with relapsed B-cell lymphoma after ≥2 prior chemoimmunotherapy regimens, representing an FDA-approved and guideline-recommended treatment option that can achieve durable remissions. 1, 2

Eligibility Criteria

Your patient qualifies for CAR-T therapy if they meet these specific requirements:

• ≥2 prior lines of chemoimmunotherapy for indolent or transformed B-cell lymphoma 1
• Disease status: Partial response (PR), non-responsive disease, or progressive disease after prior therapies 1
• Transformed follicular lymphoma: Specifically approved after ≥2 prior chemoimmunotherapy regimens for transformed disease 1
• No requirement for prior transplant: Previous autologous or allogeneic stem cell transplant is not mandatory, though allogeneic transplant is not a contraindication if the patient is off immunosuppression 2

Expected Outcomes

For standard DLBCL (which includes transformed follicular lymphoma):

• Overall response rate: 82% with 54% achieving complete response at 6 months with axicabtagene ciloleucel 3
• 2-year overall survival: 51% 3
• 2-year progression-free survival: 39% 3
• For complete responders: 12-month overall survival reaches 90% with tisagenlecleucel 3

These outcomes represent substantial improvement over salvage chemotherapy alone in heavily pretreated patients. 2

Critical Pre-Treatment Considerations

Exclude antigen-negative escape if your patient previously received bispecific antibodies or prior CAR-T therapy, as CD19-negative disease will not respond to CD19-targeted CAR-T products. 2

Performance status assessment is crucial—poor performance status more than doubles mortality risk and should be optimized before proceeding. 3

Manufacturing timeline: Plan for 2-4 weeks between leukapheresis and product availability, during which bridging therapy may be necessary if disease is rapidly progressive. 2

Toxicity Management Requirements

Cytokine release syndrome (CRS) occurs in 40-95% of patients, manifesting hours to 10-15 days post-infusion with fever, hypotension, tachycardia, hypoxia, and chills. 2

Neurotoxicity develops in 15-65% of patients, typically 1-2 weeks post-infusion, presenting as encephalopathy, delirium, aphasia, lethargy, headache, tremor, myoclonus, seizures, or potentially fatal cerebral edema. 2

Mandatory hospitalization is typically recommended for adults during the first 4 weeks after CAR-T infusion, with laboratory monitoring, vital signs, and neurological evaluation at least twice daily. 2

Treatment center requirements: Therapy must be administered at specialized centers with trained intensive care units capable of managing these life-threatening complications. 2

Alternative Considerations

Clinical trial enrollment remains the preferred option when available, as stated in NCCN guidelines for transformed disease. 1

If CAR-T is not feasible, alternative options include:

• Second-line DLBCL regimens 1
• Allogeneic stem cell transplant in selected patients 1
• Involved-site radiation therapy (ISRT) for localized residual disease 1
• Radioimmunotherapy with ibritumomab tiuxetan 1

Important Caveats

Post-CAR-T transplant data are limited. HDT/ASCR is not recommended after CAR-T therapy; allogeneic transplant could be considered but remains investigational. 1

ESMO guidelines note that CAR-T for indolent (non-transformed) follicular lymphoma is currently limited to clinical trials due to toxicity concerns, with the registered indication specifically for transformed disease. 1

Long-term remissions are achievable without subsequent transplant in patients who respond to CAR-T therapy, representing a paradigm shift from historical approaches requiring consolidative transplantation. 2