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<p>Over 60% of relapsed/refractory large B-cell lymphoma (R/R LBCL) patients treated with chimeric antigen receptor (CAR) T-cells experience progressive disease. The impact of site-specific extranodal involvement on CAR-T outcomes has not been fully elucidated. This multicenter study included 516 R/R LBCL patients infused with CD19-targeted CAR T-cells; 177 (34%) had only-nodal (N), 66 (13%) only-extranodal (E) and 273 (53%) nodal and extranodal (NE) disease at time of CAR T-cells. The NE cohort included more patients with a poor performance status and high tumor burden. In the multivariable analysis, the NE group had a shorter progression-free survival (PFS) (HR 1.27 [95%CI 0.98–1.64], <i>p</i> = 0.07) and overall survival (HR 1.41 [95%CI 1.05–1.88], <i>p</i> = 0.02) compared to N. Conversely, we did not identify efficacy differences between N and E patients. A higher number of extranodal sites and specific organ involvement (liver, adrenal glands, pancreas), were associated with shorter PFS. Finally, extranodal involvement increased at time of relapse, displaying heterogeneous individual site clearance rates. In conclusion, patients with concomitant nodal and extranodal involvement at time of CAR-T had worse outcomes, but this cohort harbored high-risk baseline characteristics. An increasing number of extranodal sites and certain disease locations were associated with lower CAR-T efficacy.</p>

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Site-specific analysis of extranodal involvement in large B-cell lymphoma reveals distinct efficacy with chimeric antigen receptor T-cell therapy

  • 期刊论文

  • 发表日期：

    2025年4月1日

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  • Gloria Iacoboni,
  • Kai Rejeski,
  • Víctor Navarro,
  • Tom van Meerten,
  • Alex Rampotas,
  • Ana África Martín-López,
  • Mariana Bastos,
  • Ana Benzaquén,
  • Juan Luis Reguera-Ortega,
  • Cecilia Carpio,
  • Claire Roddie,
  • Lucia López-Corral,
  • Javier Delgado-Serrano,
  • Maria Landwehr,
  • Sophia Stock,
  • Pablo Silva de Tena,
  • Pau Abrisqueta,
  • Janneke de Boer,
  • Alejandro Martin Garcia-Sancho,
  • Rafael Hernani,
  • Mi Kwon,
  • Marion Subklewe,
  • Maeve O’Reilly,
  • Pere Barba

摘要

Over 60% of relapsed/refractory large B-cell lymphoma (R/R LBCL) patients treated with chimeric antigen receptor (CAR) T-cells experience progressive disease. The impact of site-specific extranodal involvement on CAR-T outcomes has not been fully elucidated. This multicenter study included 516 R/R LBCL patients infused with CD19-targeted CAR T-cells; 177 (34%) had only-nodal (N), 66 (13%) only-extranodal (E) and 273 (53%) nodal and extranodal (NE) disease at time of CAR T-cells. The NE cohort included more patients with a poor performance status and high tumor burden. In the multivariable analysis, the NE group had a shorter progression-free survival (PFS) (HR 1.27 [95%CI 0.98–1.64], p = 0.07) and overall survival (HR 1.41 [95%CI 1.05–1.88], p = 0.02) compared to N. Conversely, we did not identify efficacy differences between N and E patients. A higher number of extranodal sites and specific organ involvement (liver, adrenal glands, pancreas), were associated with shorter PFS. Finally, extranodal involvement increased at time of relapse, displaying heterogeneous individual site clearance rates. In conclusion, patients with concomitant nodal and extranodal involvement at time of CAR-T had worse outcomes, but this cohort harbored high-risk baseline characteristics. An increasing number of extranodal sites and certain disease locations were associated with lower CAR-T efficacy.