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<p>Extranodal (EN) diffuse large B-cell lymphoma (DLBCL) has been historically associated with inferior survival outcomes compared to nodal DLBCL. However, outcomes of patients with EN DLBCL following chimeric antigen receptor T-cell (CAR-T) therapy are not well established. In this multi-center retrospective cohort study, we evaluated the outcomes of patients with EN DLBCL who underwent CAR-T in the relapsed/refractory (R/R) setting. The primary objective was overall survival (OS), while secondary objectives included progression-free survival (PFS), response rates, and toxicity rates. A total of 218 patients were included in the analysis. The most common sites of EN involvement were skin/soft tissue (25%), bone (22%), and lung (17%). Overall response rate (ORR) and complete response rate (CRR) at first post-treatment evaluation were 62% (<i>n</i> = 127) and 40% (<i>n</i> = 82), respectively. Median follow-up was 3.5 years. Median PFS and OS were 4.0 months (95% CI = 3.1–7.2) and 25.7 months (95% CI = 16.1–51.6), respectively. Cytokine release syndrome (CRS) of any grade occurred in 73% (<i>n</i> = 159) of patients, and 6% (<i>n</i> = 12) had grade ≥ 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 37% (<i>n</i> = 81) of patients, and 19% (<i>n</i> = 41) developed grade ≥ 3 ICANS. In the multivariable analysis, factors that were independently prognostic of inferior OS were 3 or more lines of therapy prior to CAR-T, bulky disease at the time of CAR-T, hepatobiliary, and pancreas involvement, while refractory disease to the most recent therapy prior to CAR-T was associated with inferior PFS. Future studies should further evaluate outcomes of CAR-T in patients with specific EN sites of involvement that appear to be associated with inferior survival such as the liver and pancreas.</p>

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Impact of extranodal involvement at CAR T-cell therapy on outcomes in patients with relapsed or refractory large B-cell lymphoma—Results from a multicenter cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月21日

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  • Frederique St-Pierre,
  • Subodh Bhatta,
  • Peter G. Doukas,
  • Madeline Jenkin,
  • Kaitlin Annunzio,
  • Alexandra E. Rojek,
  • Alyssa Gibson,
  • Yun Kyoung Tiger,
  • Brittany McCall,
  • Khaled Alhamad,
  • Alec Hansen,
  • Juan P. Alderuccio,
  • Olutobi Adewale,
  • Keem Patel,
  • Asaad Trabolsi,
  • Izidore S. Lossos,
  • Lindsey Fitzgerald,
  • Thomas A. Ollila,
  • Matthew J. Matasar,
  • Justin Kline,
  • Reem Karmali,
  • Narendranath Epperla

摘要

Extranodal (EN) diffuse large B-cell lymphoma (DLBCL) has been historically associated with inferior survival outcomes compared to nodal DLBCL. However, outcomes of patients with EN DLBCL following chimeric antigen receptor T-cell (CAR-T) therapy are not well established. In this multi-center retrospective cohort study, we evaluated the outcomes of patients with EN DLBCL who underwent CAR-T in the relapsed/refractory (R/R) setting. The primary objective was overall survival (OS), while secondary objectives included progression-free survival (PFS), response rates, and toxicity rates. A total of 218 patients were included in the analysis. The most common sites of EN involvement were skin/soft tissue (25%), bone (22%), and lung (17%). Overall response rate (ORR) and complete response rate (CRR) at first post-treatment evaluation were 62% (n = 127) and 40% (n = 82), respectively. Median follow-up was 3.5 years. Median PFS and OS were 4.0 months (95% CI = 3.1–7.2) and 25.7 months (95% CI = 16.1–51.6), respectively. Cytokine release syndrome (CRS) of any grade occurred in 73% (n = 159) of patients, and 6% (n = 12) had grade ≥ 3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 37% (n = 81) of patients, and 19% (n = 41) developed grade ≥ 3 ICANS. In the multivariable analysis, factors that were independently prognostic of inferior OS were 3 or more lines of therapy prior to CAR-T, bulky disease at the time of CAR-T, hepatobiliary, and pancreas involvement, while refractory disease to the most recent therapy prior to CAR-T was associated with inferior PFS. Future studies should further evaluate outcomes of CAR-T in patients with specific EN sites of involvement that appear to be associated with inferior survival such as the liver and pancreas.