Rituximab maintenance therapy in diffuse large B-cell lymphoma: is XY the most important variable?

I n B-cell non-Hodgkin lymphomas (NHL) rituximab has extended the disease-free intervals of hundreds of thousands of patients. At the inception of rituximab a considerable amount of academic vigor was invested in finding the appropriate dose and frequency during induction therapy. This was followed by consideration of rituximab maintenance or extended dosing strategies. However, if maintenance rituximab does not significantly improve treatment outcomes it only represents expensive plasma. An integral step in harnessing the excitement for maintenance ritux-imab is to look for patients' characteristics that can help to tailor or risk-adapt rituximab dose and/or duration of use with the goal of providing benefit to all. The primary end-point of interest, improvement in overall survival, has only been seen in meta-analyses, leaving surrogate markers of benefit, such as event-free survival and progression-free survival in trials, to be debated at podiums and in patients' examination rooms without a clear consensus being reached. 1 The original report that triggered the spark of enthusiasm for maintenance rituximab was published by Dr. Ghielmini and colleagues and concerned patients with fol-licular lymphoma (FL) in whom prolonged rituximab treatment extended the duration of remission. 2 The use of rituximab in FL subsequently expanded as results of ran-domized trials emerged showing remission prolongation with maintenance rituximab after single agent rituximab and combined rituximab-chemotherapy and then similar results in mantle cell lymphoma. 3-7 A theme began to develop: rituximab maintenance was most useful in B-cell NHL subtypes in which the majority of patients do not have durable remissions. However, in diffuse large B-cell lymphoma (DLBCL), the most common NHL, in which the majority of patients who achieve a complete remission after rituximab-chemotherapy are cured, maintenance rit-uximab therapy has not been felt to be efficacious. Nevertheless, Huang and colleagues reported a random-ized trial of maintenance rituximab in patients with an objective response after six cycles of R-CHOP-14 (ritux-imab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The maintenance rituximab was administered monthly during the first 12 months and once every 3 months during the second year. 8 Patients who received maintenance rituximab had a progression-free survival rate at 5 years of 45% compared to 34% in the patients who were observed (P=0.006). The overall survival rate at 5 years was 62% with maintenance rituximab and 49% with observation (P=0.03). Maintenance rituximab improved the progression-free and overall survival of patients in all International Prognostic Index groupings. The lower progression-free and overall survival rates might …