577 Biopsy-associated tumor regression in late relapsed DLBCL after tandem CD20-CD19 CAR-T cell therapy
Year: 2026
Type: conference-abstract
Abstract: Background CAR T-cell therapy revolutionized relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) treatment, yet 40–50% of patients progress. Clinical responses can be delayed, such that standard-of-care salvage therapy is administered before immunological maximum benefit, generally seen early after CAR T therapy. Isolated late solitary relapse can be challenging regarding optimal management. A case is presented of complete metabolic response following core needle biopsy >18 months after infusion of tandem CD20-CD19 CAR T therapy.Methods A 59-year-old female with r/r DLBCL (IPI: stage 4; high tumor volume) received zamtocabtagene autoleucel (zamto-cel) in third line after failing R-CHOP/R-ICE ( NCT04792489). Zamto-cel is manufactured using CliniMACS Prodigy® (Miltenyi Biotec), a closed, automated system with 14-day vein-to-vein time and administered as a fresh formulation. Lymphodepletion chemotherapy was initiated during the manufacturing process. Day 30 evaluation revealed CMR that persisted through year 1 when an isolated retrocaval signal was observed at month 14 (Deauville 4/X; SUVmax: 5.6) suggesting a sanctuary relapse. Participant followed expectantly, but with evidence of progression, (Deauville 5; SUVmax: 16.8) core needle biopsy performed at month 19 confirmed progression. Subsequent salvage therapy deferred due to patient preference, creating a window of observation. Serial PET/CT imaging was performed at 21, 25 and 36 months to assess response kinetics, CT imaging obtained at 48 months.Results At month 19, biopsy confirmed recurrent germinal center B-cell DLBCL (Ki-67 80%). Immunophenotype was CD20 +, variable CD19, CD10+, CD79a+, BCL6+, and BCL2+ expression. Immune reconstitution studies at year 1 revealed total CD3: 562/uL, CD4: 358/uL and B-cell: 73/uL. Two months post-biopsy (month 21), prior to the onset of salvage XRT, PET imaging demonstrated a 38% decrease in the sum of product diameters (SPD). Continued observation was elected and by month 25, the participant achieved CMR (Deauville 1–2) across all sites without chemotherapy, radiation, or other immunotherapies. The patient remains with no clinical evidence of active disease at month 48.Conclusions This case demonstrates a rare biopsy-induced, confirmed tumor site regression in the late post-CAR T setting. No local or systemic therapies were administered. Localized tissue injury, via damage-associated molecular patterns (DAMPs) and pro-inflammatory cytokines, may trigger delayed reactivation of exhausted, previously trafficked CAR T cells. Late-stage immune reconstitution and/or functional activation of residual CAR T cells contributed to clinical response. This case highlights the possibility of preempting spontaneous responses with immediate application of salvage therapy. Identifying signals of delayed CAR T reactivation may eliminate need for subsequent treatments.
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
OpenAlex ID: W7225329616