Outcomes of patients with relapsed or refractory primary mediastinal B-cell lymphoma treated with anti-CD19 CAR-T cells: CARTHYM, a study from the French national DESCAR-T registry.

in HemaSphere by Jean Galtier, Charles Mesguich, Pierre Sesques, Vivien Dupont, Emmanuel Bachy, Roberta Di Blasi, Catherine Thieblemont, Thomas Gastinne, Guillaume Cartron, Gabriel Brisou, François-Xavier Gros, Justine Decroocq, Franck Morschhauser, Marie-Thérèse Rubio, Laurianne Drieu La Rochelle, Fabien Le Bras, Sylvain Carras, Adrien Chauchet, Jacques-Olivier Bay, Magalie Joris, Mickael Loschi, Aline Tanguy-Schmidt, Alexandra Marquet, Vincent Camus, Steven Le Gouill, Roch Houot, Krimo Bouabdallah

TLDR

  • Anti-CD19 CAR-T cell therapy demonstrates promising outcomes in relapsed or refractory primary mediastinal B-cell lymphoma (PMBL), with a best complete response rate of 68.1% and 2-year overall survival of 73.8%.
  • Key determinants of treatment success include achieving a Deauville score of 1-4 or a ΔSUVmax reduction of more than 24% at the 1-month evaluation, and increasing total metabolic tumor volume baseline PET.

Abstract

Primary mediastinal B-cell lymphoma (PMBL) is often cured with dose-dense anthracycline-based regimens but the prognosis at relapse or progression remains poor. While anti-CD19 CAR-T cell therapy has dramatically improved outcomes in relapsed or refractory large B-cell lymphoma, far less is known about their efficacy in PMBL. Using the systematic record of all patients treated with CAR-T cells prospectively included in the DESCAR-T registry in France, along with centrally reviewed positon-emission tomography (PET) imaging, we describe the outcomes and key determinants of treatment success in PMBL patients treated over a 6-year period. Among 82 patients infused in the registry we observed a best complete response (CR) rate, 2-year progression-free survival (PFS), and 2-year overall survival (OS) of 68.1%, 57.4%, and 73.8%, respectively. Outcomes were even better for the 62 patients infused with axicabtagene ciloleucel, with best CR rate, 2-year PFS, and 2-year OS reaching 74.5%, 70.4%, and 86.9%, respectively. Achieving a Deauville score of 1-4 or a ΔSUVmax reduction of more than 24% at the 1-month evaluation was associated with excellent outcomes, whereas increased total metabolic tumor volume baseline PET increased the risk of treatment failure. Surprisingly, neither the response to bridging therapy nor the type of bridging therapy (chemotherapy versus immune checkpoint inhibitors) were associated with long-term outcomes. In conclusion, this study confirms that anti-CD19 CAR-T cells as a valid standard-of-care for relapsed and refractory PMBL and highlights key determinants of treatment success.

Overview

  • The study investigated the efficacy of anti-CD19 CAR-T cell therapy in relapsed or refractory primary mediastinal B-cell lymphoma (PMBL) patients.
  • The study analyzed the outcomes and key determinants of treatment success in PMBL patients treated with CAR-T cells over a 6-year period, using the DESCAR-T registry in France.
  • The primary objective was to explore the potential of CAR-T cells as a standard-of-care treatment for relapsed and refractory PMBL.

Comparative Analysis & Findings

  • Among 82 patients infused in the registry, the best complete response rate, 2-year progression-free survival, and 2-year overall survival were 68.1%, 57.4%, and 73.8%, respectively.
  • Outcomes were better for the 62 patients infused with axicabtagene ciloleucel, with best CR rate, 2-year PFS, and 2-year OS reaching 74.5%, 70.4%, and 86.9%, respectively.
  • Achieving a Deauville score of 1-4 or a ΔSUVmax reduction of more than 24% at the 1-month evaluation was associated with excellent outcomes, whereas increased total metabolic tumor volume baseline PET increased the risk of treatment failure.

Implications and Future Directions

  • The study confirms that anti-CD19 CAR-T cells are a valid standard-of-care for relapsed and refractory PMBL, offering promising outcomes.
  • Future studies may focus on identifying biomarkers to improve treatment selection and outcomes, as well as exploring novel combination therapies to enhance CAR-T cell efficacy.
  • The findings highlight the need to integrate PET imaging into clinical practice to monitor treatment response and outcomes in PMBL patients.
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