Efficacy and safety of CAR T-cell therapy in patients with primary or secondary CNS lymphoma: A study on behalf of the EBMT and the GoCART coalition.

in HemaSphere by Anna Ossami Saidy, Christophe Peczynski, Catherine Thieblemont, Michael Daskalakis, Marc Wehrli, David Beauvais, Jürgen Finke, Elisabeth Schorb, Peter Vandenberghe, Philipp Berning, Matthias Stelljes, Francis Ayuk, Ron Ram, Malte Von Bonin, Peter Dreger, Wolfgang Bethge, Andrea Kuhnl, Lasse Jost, Friedrich Stölzel, Bastian von Tresckow, Christoph Renner, Stephan Fuhrmann, Jacques-Emmanuelle Galimard, Eva Michel, Ali Bazarbachi, Anna Sureda Balari, Norbert Schmitz, Bertram Glass

TLDR

  • The study analyzed data from 100 patients with CNS manifestation treated with CAR T-cell therapy and found that it can be effective in treating r/r PCNSL and SCNSL, but with serious side effects.
  • Elevated lactate dehydrogenase was an independent risk factor for relapse and progression-free survival.

Abstract

Patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary central nervous system (CNS) lymphoma (SCNSL) face a dismal prognosis. They have been excluded from most clinical CAR T-cell trials as investigators feared an increased risk for severe immune effector cell-associated neurotoxicity (ICANS). To investigate the potential of anti-CD19 CAR T-cell therapy (CART) in such patients, we analyzed data of 100 patients with CNS manifestation treated with CART between January 2018 and July 2023 and reported to European Society for Blood and Marrow Transplantation. Median age was 62 years. Of patients, 58% had failed ≥3 treatment lines, and 40% had received autologous stem-cell transplantation before CART. Fifty-nine patients received axicabtagene ciloleucel, 38 patients were treated with tisagenlecleucel, three patients received other products. At the time of CART, 67 patients had active CNS disease. Overall and progression-free survival (PFS) at 24 months were 37% and 28%. Relapse incidence (RI) at 24 months was 59%, whereas non-relapse mortality at 1 year was 7%. Cytokine release syndrome (CRS) and ICANS of any grade occurred in 83% and 42% of patients, respectively. CRS grade 3 occurred in 11 and ICANS grades 3-4 in 17 patients. Two patients died of neurotoxicity. Elevated lactate dehydrogenase was an independent risk factor for RI and PFS (hazard ratio [HR] 2.4,= 0.003; HR: 1.9,= 0.016). Patients with ECOG 2-3 had a significantly increased risk for the development of ICANS (HR 2.68,= 0.002). These data support the implementation of CART as treatment for patients with r/r PCNSL and SCNSL.

Overview

  • The study analyzed data of 100 patients with CNS manifestation treated with anti-CD19 CAR T-cell therapy (CART) between January 2018 and July 2023.
  • The median age of the patients was 62 years, with 58% having failed ≥3 treatment lines and 40% having received autologous stem-cell transplantation before CART.
  • The primary objective of the study was to investigate the potential of anti-CD19 CAR T-cell therapy in patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary central nervous system (CNS) lymphoma (SCNSL).

Comparative Analysis & Findings

  • The overall and progression-free survival (PFS) at 24 months were 37% and 28%, respectively, with a relapse incidence (RI) at 24 months of 59%.
  • Elevated lactate dehydrogenase was an independent risk factor for relapse incidence and PFS.
  • Patients with Eastern Cooperative Oncology Group (ECOG) 2-3 had a significantly increased risk for the development of immune effector cell-associated neurotoxicity (ICANS).

Implications and Future Directions

  • The study's findings support the implementation of CAR T-cell therapy as a treatment option for patients with r/r PCNSL and SCNSL.
  • Further research is needed to address the limitations of the study, including the lack of standardization in CAR T-cell product and dosing, and the need for improved management of neurotoxicity.
  • Future studies should explore the use of CAR T-cell therapy in combination with other treatment modalities, such as radiotherapy, to improve outcomes for patients with r/r PCNSL and SCNSL.
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