CELL INTELLIGENCE · 肿瘤细胞治疗研究

Background Patients with relapsed or refractory (R/R) follicular lymphoma (FL) after two or more prior lines of therapy can now be treated with mechanistically distinct modalities, including CD19-directed chimeric antigen receptor (CAR) T-cell therapy, CD20 CD3 bispecific antibodies, and a Bruton tyrosine kinase inhibitor plus anti-CD20 combination. Head-to-head data are lacking, and sequencing decisions are made with limited comparative evidence.

We benchmarked durability outcomes across pivotal trials using reconstructed individual patient data (rIPD) derived from published Kaplan-Meier (KM) curves.

Methods KM curves and numbers-at-risk tables from pivotal prospective studies in 2-line R/R FL were digitized and rIPD-reconstructed using a validated algorithm: axicabtagene ciloleucel (ZUMA-5), tisagenlecleucel (ELARA), lisocabtagene maraleucel (TRANSCEND FL), mosunetuzumab, epcoritamab (EPCORE NHL-1), and zanubrutinib plus obinutuzumab versus obinutuzumab (ROSEWOOD). Prespecified durability endpoints were landmark progression-free survival (PFS) at 12 and 24 months and restricted mean survival time to 24 months (RMST24).

Overall survival (OS) landmarks were summarized where follow-up permitted. ROSEWOOD served as an internal validity check using a Cox model fit to reconstructed data. Results At 24 months, landmark PFS was 65. 4% (95% confidence interval (CI) 52. 0-82. 4) for liso-cel, 62. 0% (50. 2-76. 6) for axi-cel, 53. 8% (45. 2-63. 9) for zanubrutinib plus obinutuzumab, 49. 3% (39. 3-61. 7) for mosunetuzumab, 43. 7% (31. 3-61. 1) for epcoritamab, and 24. 7% (14. 9-40. 9) for obinutuzumab monotherapy. Twelve-month PFS ranged from 81. 8% (74. 5-89. 8) with liso-cel and 77. 9% (69. 4-87. 5) with axi-cel to 61. 6% (53. 6-70. 8), 60. 4% (50. 8-72. 0), and 59. 1% (50. 5-69. 1) for zanubrutinib plus obinutuzumab, mosunetuzumab, and epcoritamab, respectively; tisagenlecleucel showed 12-month PFS of 68. 3% (57. 2-81. 6) with shorter follow-up (maximum 18. 2 months). PFS RMST24 estimates were 19. 5 months for liso-cel, 18. 6 for axi-cel, 16. 5 for zanubrutinib plus obinutuzumab, 16. 2 for mosunetuzumab, 14. 8 for epcoritamab, and 11. 9 for obinutuzumab. OS at 24 months was high across regimens (mosunetuzumab 87. 3%, liso-cel 84. 6%, axi-cel 82. 8%, zanubrutinib plus obinutuzumab 77.

3%, and epcoritamab 67. 6%). In ROSEWOOD, reconstructed data reproduced the published PFS benefit for zanubrutinib plus obinutuzumab (hazard ratio (HR) 0. 48, 95% CI 0. 32-0. 71; p < 0. 001) with a weaker OS signal (HR 0. 61, 0. 35-1. 07; p = 0. 08). Conclusions In this rIPD-based durability benchmark for 2-line R/R FL, the estimated landmark PFS and RMST24 values varied across regimens, with numerically higher point estimates for the CAR T-cell therapies and the zanubrutinib plus obinutuzumab combination and numerically lower estimates for the bispecific antibodies and the obinutuzumab control; CIs overlapped substantially, and 24-month OS estimates were broadly similar across regimens.

Because the source trials enrolled materially different populations, these side-by-side estimates are descriptive benchmarks and should not be read as head-to-head comparisons of efficacy. Faithful internal reproduction of the randomized ROSEWOOD effect supports reconstruction fidelity. The analysis provides a transparent, durability-focused reference framework to support sequencing discussions and hypothesis generation, not comparative effectiveness conclusions.