From Stem Cell Transplantation to CAR-T Therapy in Relapse-Refractory Diffuse Large B-Cell Lymphoma

Abstract

Diffuse large B-cell lymphoma is a highly curable disease when complete remission after immunochemotherapy is achieved. Despite a high complete remission rate, which is a prerequisite for a cure, 20–40% of patients will relapse or fail first-line therapy. Salvage chemotherapy followed by intensification with autologous stem cell transplant (ASCT) has been established as a curative treatment for relapsed chemosensitive patients under 60 years of age. The results have been somewhat disappointing, with less than 50% of patients being eligible for transplant and relapse posttransplant ranging from 60–40%. Improvements have been made with new drugs in development, immunoconjugate bispecific monoclonal antibodies, and chimeric antigen receptor technology (CAR-T). A more precise evaluation of prognostic factors with PET scans and other biological factors during treatment will allow for the design of new treatment strategies. The exceptional response rate in phase 2 achieved with the three available CARTs has now been confirmed with a longer follow-up period. At 2 years, the overall survival (OS) expectancy is 50% with a plateau on the curves. Three randomized studies compared CARTs to the standard of care with ASCT and demonstrated the superiority of CARTs. Despite this superiority, the relapse rate remains 50%, which is significantly better than the standard of care. However, major improvements in OS have not yet been achieved. A clearer definition of eligible patients should also take into account their interim pet-scan, metabolic tumour volume, relation with Ct DNA with follow-up of minimal residual disease.