Antibody-based therapy of non-Hodgkinʹs lymphoma

Monoclonal antibodies (mAb) have dramatically advanced our ability to treat non-Hodgkinʹs lymphoma (NHL), and there has been a virtual explosion of clinical data regarding their use. Rituximab is a humanized anti-CD20 mAb and has significant single agent activity in follicular lymphoma, and to a lesser extent in mantle-cell and diffuse large B-cell lymphoma (DLCL). Rituximab appears to have synergistic activity with cytotoxic chemotherapy and the combination has recently demonstrated improved rates of complete remission (CR) and overall survival in older patients with DLCL. Alemtuzumab (Campath-1H) is a humanized mAb targeting CD52 and has recently been approved in the USA for the treatment of fludarabine-refractory B-cell chronic lymphocytic leukaemia. Impressive activity has also been demonstrated in T-cell prolymphocytic leukaemia and mycosis fungoides. The radioconjugated anti-CD20 mAbs ibritumomab tiuxetan and I131-tositumomab also have impressive clinical activity in low-grade B-cell NHL, and the former has demonstrated superior CR rates to rituximab. Myelosuppression is more significant however, and their place in the treatment algorithm remains to be clearly defined. Other immunotoxins (e.g. BL22) and mAb against alternate targets (e.g. epratuzumab, humanized anti-CD22) are in development