Paper Details

ABSTRACT

Background

Chimeric antigen receptor (CAR) T-cell therapy is the standard of care for patients with large B-cell lymphoma (LBCL) with primary refractory disease or relapse within 12 months after first-line chemoimmunotherapy (CIT). In contrast, patients relapsing at a later timepoint represent a clinically heterogeneous population for whom prospective evidence specifically evaluating CAR T-cell therapy is limited.

Methods

LATE-R is an academic, open-label, multicenter, single-arm phase II trial sponsored by GELTAMO in collaboration with Kite, a Gilead Company, designed to evaluate the efficacy and safety of axicabtagene ciloleucel (axi-cel) in patients with late-relapsing LBCL. Eligible patients were ≥18 years with either diffuse large B-cell lymphoma (DLBCL), transformed follicular lymphoma, follicular lymphoma grade 3B (FL3B), or high-grade B-cell lymphoma (HGBL), with biopsy-proven relapse 12–60 months after completing first-line CIT and no previous second-line treatment. Bridging therapy was permitted. The primary endpoint was complete response (CR) rate 3 months after axi-cel infusion, assessed locally by PET-CT. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. This second pre-specified interim analysis included data available as of May 2026.

Results

On April 1, 2026, enrollment was completed after inclusion of the planned 45 patients. Three patients discontinued before infusion because of an adverse event (hip fracture unrelated to lymphoma), withdrawal of consent, and diagnostic revision, respectively. Of the remaining 42 patients, 41 had received axi-cel by the data cutoff and were included in the present analysis.

Median age was 65 years (range, 28–79), and 23 patients (56.1%) were male. At study entry, 30 patients (73%) had DLBCL, 10 (24%) had HGBL, including 9 (22%) with MYC and BCL2 rearrangements, and 1 (2%) had FL3B. Thirty-one patients (76%) had Ann Arbor stage III–IV, 16 (39%) an International Prognostic Index (IPI) of 3–5, and 8 (19%) bulky disease. Relapse occurred 12–24 months after first-line CIT in 24 patients (58.5%) and 24–60 months after CIT in 17 (41.5%). Median time from consent to leukapheresis was 18 days (Q1–Q3, 11–22), and from leukapheresis to infusion was 41 days (Q1–Q3, 33–46). Bridging therapy was administered to 39 patients (95%).

Among the 37 patients evaluable for best response, 35 (94.6%) achieved CR and 2 PR, resulting in an ORR of 100%; 4 infused patients had not yet reached the first response assessment at the data cutoff. Among the 34 patients evaluable at month 3, the CR rate was 85.3% (95% CI, 64.1–95.0). After a median follow-up of 7.5 months (Q1–Q3, 4.0–11.9), median PFS and OS were not reached. Estimated 6-month PFS and OS were 90.9% (95% CI, 74.4–97.0) and 97.2% (95% CI, 81.9–99.6), respectively.

All patients experienced at least one adverse event (AE), and 56.1% experienced at least one serious AE. The most frequent grade ≥3 AEs (occurring in ≥10% of patients) were neutropenia / neutrophil count decreased (65.8%), thrombocytopenia / platelet count decreased (39.1%), immune effector cell-associated neurotoxicity syndrome (ICANS; 26.9%), and anemia (24.4%). Regarding AEs of special interest (AESIs), CRS was predominantly grade 1 (48.8%) and grade 2 (34.1%), with grade 3 events in 7.3% of patients and no grade 4 or 5 events. ICANS was reported in 51.2% of patients, with grade 1, 2, 3, and 4 events occurring in 17.1%, 7.3%, 17.1%, and 9.8% of patients, respectively; no grade 5 neurotoxicity was observed. Grade ≥3 hematologic toxicities occurring beyond month 1 included neutropenia (36.6%), thrombocytopenia (29.3%), and anemia (12.2%). Grade ≥3 infections occurred in 7 patients (17.1%), including one fatal septic shock 34 days after axi-cel infusion.

Conclusions