Resultados y factores pronósticos de pacientes con síndromes linfoproliferativos que reciben tratamiento con linfocitos T con receptor de antígeno quimérico

• Autores: Gloria Iacoboni
• Directores de la Tesis: Francesc Bosch Albareda (dir. tes.), Pere Barba Suñol (codir. tes.)
• Lectura: En la Universitat Autònoma de Barcelona ( España ) en 2023
• Idioma: español
• Tribunal Calificador de la Tesis: David Valcarcel Ferreiras (presid.), María José Terol Castera (secret.), Carlos Panizo Santos (voc.)
• Programa de doctorado: Programa de Doctorado en Medicina por la Universidad Autónoma de Barcelona
• Materias:
  • Ciencias médicas
    • Medicina interna
      • Hematología
• Enlaces
  • Tesis en acceso abierto en: TDX
• Resumen

  • The dismal prognosis of patients with relapsed/refractory large B-cell lymphoma has significantly improved since the advent of CAR T-cell therapy. Despite these enormous advances, approximately 60% of infused patients will eventually progress, which is associated with a median overall survival of 6 months and response rates to salvage strategies inferior to 25%. Finally, CAR T-cell therapy is not devoid of short and/or long-term toxicity that diminish the survival of some patients. Altogether, it is beyond doubt that a careful patient selection is key to identify which candidates have a higher chance of benefitting from CAR-T therapy.

    The Doctoral Thesis presented herein is composed by three clinical studies analyzing real-world data of axi-cel and tisa-cel CAR-T therapies. In all of them, a similar safety profile to the pivotal trials was observed, although a higher use of tocilizumab and steroids led to a lower incidence of severe CRS and ICANS. Among products, patients treated with axi-cel had higher rates of CRS and ICANS then tisa-cel recipients, leading to an increased use of immunosuppressive agents, hospital stay and infections. Patients with increased serum LDH, more than 2 prior lines of treatment or those harboring a poor PS presented an increased risk of severe CRS and/or ICANS.

    Regarding efficacy, the response rates and survival outcomes were comparable to the pivotal trials. There were no significant differences in survival between both products in the modified intention to treat analysis. Among pretreatment characteristics associated with efficacy, we identified high LDH levels, TMTV values and a poor PS to be associated with a worse PFS. The 1-month post-infusion assessment was predictive of CAR T-cell outcomes and identified patients in partial remission at high risk of disease progression.

    In conclusion, the three studies that represent the body of this doctoral thesis accomplished to identify variables that prior or after CAR-T infusion are able to predict the outcome of patients receiving these therapies.