Journal: Blood advances
This multicenter retrospective study assessed real-world outcomes of CD19-directed CAR T-cell therapy in 466 patients with de novo diffuse large B-cell lymphoma or transformed follicular lymphoma, stratified by line of therapy: second line (2L, 21%), third line (3L, 41%), and fourth line or later (4L+, 38%). Median follow-up was 35 months.
Key findings:
- Response rates: Overall and complete response rates were similar across 2L, 3L, and 4L+ use.
- Survival by line of therapy:
- Median PFS: 11.6 months (2L) vs 12.7 months (3L) vs 5.7 months (4L+), P < .001.
- Median OS: not reached (2L) vs 69.4 months (3L) vs 21.9 months (4L+), P < .001.
- This indicates comparable outcomes when CAR T is used in 2L vs 3L in unselected patients, but substantially worse outcomes when deferred to 4L+.
- High-risk biology (DHL/THL):
- For double-hit/triple-hit lymphoma, earlier use mattered: 3-year OS was 63% in 2L vs 32% in 3L (P = .01), favoring 2L.
- Bridging therapy:
- Need for bridging therapy was associated with higher risk of progression or death, suggesting it is a negative prognostic marker.
Clinical implications:
- Overall LBCL population: In routine practice, CAR T in 2L and 3L yields broadly similar survival.
- Double-hit/triple-hit disease: CAR T should be prioritized earlier (in 2L) outside the classic primary refractory or early relapse indications.
- Later-line use: Deferring CAR T to 4L or later is associated with markedly inferior PFS and OS.