Response rates of extra-nodal diffuse large B cell lymphoma to anti-CD19-CAR T cells: A real word retrospective multicenter study

Ofrat Beyar Katz, Chava Perry, Sigal Grisariu-Greenzaid, Dana Yehudai-Ofir, Efrat Luttwak, Batia Avni, Tsila Zuckerman, Inbal Sdayoor, Polina Stepensky, Shimrit Ringelstein-Harlev, Yael Bar-On, Diana Libster, Liat Sharvit, Odelia Amit, Uri Greenbaum, Ronit Gold, Yair Herishanu, Noam Benyamini, Irit Avivi, Ron Ram

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Chimeric antigen receptor T-cells (CAR-T) are widely used for the treatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data for CAR-T cell therapy in patients with extra-nodal (EN) lymphoma is restricted. We included 126 consecutive patients with DLBCL treated with commercially available CAR-T cells (tisagenlecleucel, n = 100, 79.4% and axicabtagene ciloleucel, n = 26, 20.6%). At lymphodepletion, 72 of 126 (57%) patients had EN disease, 42 of 126 (33%) patients had nodal disease (ND)-only and 12 of 126 (10%) showed no disease assessed by PET-CT. There were no significant differences in CAR-T related toxicities and in the median Progression free survival (PFS) between EN patients and ND (10.76 [95% CI: 7.8–13.6] vs. 14.1 [95% CI: 10–18.1] months, p =.126). Similarly, median overall survival (OS) was not significantly different (15.36 [95% CI 12.5–18.2] vs. 18.4 [95% CI 14.8–22.1] months, p =.100). Subgroup analysis according to the number of EN involved sites showed that median PFS and OS were significantly higher in patients with <3 EN sites (12.3 months [95% CI 9–15.5] vs. 4.28 months [95% CI 0.6–7.9], p =.010) compared to patients with >2 EN sites, respectively (16.5 months [95% CI 13.4–19.6] vs. 8.7 months [95% CI 4.6–12.8], p =.05). In multivariate cox regression analysis, increased number sites of EN disease and high lactate dehydrogenase (LDH) at lymphodepletion negatively impacted PFS (p =.021 and <.001, respectively), while sex, type of product administered, age and performance status did not predict PFS and OS. Of note, all the patients with involvement of gastrointestinal tract (n = 9), urinary tract (n = 9), or pharynx (n = 3) at lymphodepletion, progressed or had an early relapse. In conclusions, patients with >2 EN sites at lymphodepletion have significantly worse clinical outcomes compared to patients with <3 EN sites. Patients with specific sites of EN disease may demonstrate grim prognosis.

Original languageEnglish
Pages (from-to)63-71
Number of pages9
JournalEuropean Journal of Haematology
Volume111
Issue number1
DOIs
StatePublished - 1 Jul 2023
Externally publishedYes

Keywords

  • CAR-T cells
  • extra-nodal
  • lymphoma

ASJC Scopus subject areas

  • Hematology

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