What are the survival rates for an adult patient with stage 4 T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) undergoing Chimeric Antigen Receptor T-cell (CAR-T) therapy?

Survival Rates After CAR-T Therapy for Stage 4 THRLBCL

For adults with stage 4 T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) treated with CAR-T therapy, approximately 29% remain progression-free and 42% remain alive at 2 years, though these outcomes are notably inferior to standard DLBCL. 1

Key Survival Data for THRLBCL-Specific CAR-T Outcomes

The most recent and highest-quality evidence specifically addressing THRLBCL comes from the Center for International Blood and Marrow Transplant Research registry analysis of 58 patients with relapsed/refractory THRLBCL treated with commercial CD19-CAR-T therapy between 2018-2022 1:

Primary Survival Metrics

• 2-year overall survival: 42% (95% CI, 27-57%) 1
• 2-year progression-free survival: 29% (95% CI, 17-43%) 1
• 2-year cumulative incidence of relapse/progression: 69% 1
• Median follow-up: 23 months 1

Patient Characteristics in This Cohort

• 67% had early disease relapse (45% primary refractory) 1
• Median of 3 prior therapies (range 1-7) 1
• 69% treated with axicabtagene ciloleucel 1
• Poor performance status before CAR-T was associated with higher mortality (HR 2.35; 95% CI, 1.02-5.5) 1

Comparison to Standard DLBCL CAR-T Outcomes

THRLBCL demonstrates substantially worse outcomes compared to standard DLBCL treated with CAR-T therapy. For context, NCCN guidelines report that standard DLBCL patients treated with axicabtagene ciloleucel achieve 2:

• 2-year overall survival: 51% (versus 42% for THRLBCL) 2
• 2-year progression-free survival: 39% (versus 29% for THRLBCL) 2
• Overall response rate: 82% with 54% complete response at 6 months 2

The tisagenlecleucel data for standard DLBCL shows 12-month overall survival of 49% for all patients and 90% for those achieving complete response 2.

Critical Prognostic Factors

Pre-CAR-T Performance Status

Performance status before CAR-T infusion is the most significant modifiable prognostic factor, with poor performance status more than doubling mortality risk 1.

Disease Characteristics

• Primary refractory disease (45% of THRLBCL cohort) carries particularly poor prognosis 1
• Early relapse (<12 months from initial therapy) is common in THRLBCL 1
• Stage 4 disease with extensive tumor burden may impact outcomes 1

Toxicity Profile

Despite inferior efficacy, THRLBCL patients experience similar toxicity rates to standard DLBCL 1:

• Grade ≥3 cytokine release syndrome: 7% 1
• Grade ≥3 immune effector cell-associated neurologic syndrome: 15% 1
• 2-year non-relapse mortality: 2% 1

These toxicity rates are comparable to or lower than standard DLBCL populations where CRS occurs in 40-95% (any grade) and neurologic toxicity in 15-65% 3.

Clinical Implications and Treatment Algorithm

When to Consider CAR-T for Stage 4 THRLBCL

CAR-T therapy should be offered to patients with relapsed/refractory stage 4 THRLBCL after ≥2 prior lines of therapy, particularly those with good performance status, as approximately 30% achieve durable remissions despite the high relapse rate. 1

Patient Selection Criteria

1. Performance status assessment is mandatory—only proceed in patients with adequate performance status given the 2.35-fold increased mortality with poor performance 1
2. Prior therapy burden—most successful patients had median of 3 prior therapies 1
3. Disease characteristics—primary refractory disease portends worse outcomes but does not preclude CAR-T 1

Alternative Considerations

For newly diagnosed THRLBCL, recent data suggests higher-intensity frontline regimens (R-CHOP/R-ICE) achieve superior outcomes with 5-year event-free survival of 80% and overall survival of 100%, compared to standard R-CHOP (50% and 72% respectively) 4. This suggests that optimizing frontline therapy may reduce the need for CAR-T in this population.

Common Pitfalls to Avoid

• Do not assume THRLBCL will respond like standard DLBCL—the 2-year progression-free survival of 29% is substantially lower than the 39% seen in standard DLBCL 1, 2
• Do not proceed with CAR-T in patients with poor performance status without careful discussion—mortality risk more than doubles 1
• Do not dismiss CAR-T entirely based on lower response rates—approximately 30% of patients achieve durable remissions, which exceeds outcomes with conventional salvage chemotherapy 1
• Do not delay CAR-T referral in eligible patients—the 2-year cumulative incidence of relapse/progression is 69%, emphasizing the aggressive nature of this disease 1