Journal: Blood advances
This study uses the French DESCAR-T real-world registry to characterize patients with large B‑cell lymphoma (LBCL) who experience late failure after anti‑CD19 CAR T‑cell therapy, defined as relapse or progression occurring more than 3 months post-infusion.
Key patient characteristics:
- • 298 late-failure patients (39.9% of all LBCL failures) identified between 2018–2024
- • Median age 62 years; 61.7% male
- • Predominantly diffuse LBCL (68.8%), advanced stage (84.6%), and high-risk disease at CAR T eligibility (aaIPI 2–3 in 59.3%)
Post–CAR T treatment and outcomes:
- • After late failure, 76.5% received at least one systemic therapy
- • Overall response rate to post-failure systemic therapies: 22.6%, with 18% complete responses
- • With median follow-up of 13.8 months from first late-failure event:
- • Median overall survival: 4.4 months
- • Median PFS2 (from start of first post-failure therapy to progression/death): 13.2 months
Comparative effectiveness of salvage strategies:
- • Bispecific antibodies (bsAb) as salvage were associated with superior PFS2 compared with:
- • Chemotherapy (HR 0.350; 95% CI 0.193–0.633)
- • A pooled group of other non-bsAb treatments (HR 0.483; 95% CI 0.290–0.805)
- • Radiotherapy provided durable benefit in a subset, with 12‑month PFS2 of 41.5% (95% CI 22.5–59.5)
Clinical implications:
- • Even among patients relapsing late after CAR T, prognosis remains poor, with short overall survival after first failure.
- • Bispecific antibodies appear more effective than chemotherapy and other strategies in this specific late-failure setting and should be prioritized in treatment planning and in the design of future clinical trials.
- • Radiotherapy can offer meaningful disease control in selected patients, supporting its continued consideration in localized or oligoprogressive late relapses.