Unresolved issues in diffuse large B-cell lymphomas

Abstract

For more than 25 years, the combination of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was considered the ‘gold standard’ for the treatment of aggressive lymphomas, 90% of which are diffuse large B-cell lymphomas (DLBCLs). After the demonstration of rituximab’s single-agent activity in DLBCL, a pivotal trial in elderly patients demonstrated that combining rituximab with eight applications of CHOP significantly improved complete remission rates, and event-free and overall survival rates compared with CHOP alone. These positive results have meanwhile been confirmed by two additional randomized trials and have been extended to young patients with good-prognosis DLBCL by a fourth trial and rituximab, in combination with CHOP, has become accepted worldwide as the new standard for all DLBCL. Remaining issues concern biology-based approaches and the guidance of therapy by PET, the definition of the optimal dosage and schedule of rituximab for DLBCL, as well as the optimal chemotherapy regimen partner for rituximab. Finally, patients failing after rituximab-containing immunochemotherapy have a dismal prognosis and the treatment of these patients has become a prime challenge in the rituximab era.

Keywords::

• aggressive lymphoma
• CD20 antigen
• chemotherapy
• diffuse large B-cell lymphoma
• high-dose chemotherapy
• immunotherapy
• monoclonal antibody
• PET
• rituximab
• targeted therapy
• transplantation

Financial & competing interests disclosure

Michael Pfreundschuh is on the Roche Mabthera Advisory Board and has received unrestricted grants from Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.