Reviewer: Neha Vapiwala, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 5, 2004
This presentation discusses the off-label use of rituximab for the treatment of indolent NHL.Presenter: H.S. Hochster
Indolent lymphomas (IL), as the name implies, have a "waxing and waning" pattern featuring multiple disease relapses over a large time period. It is not typically aggressive or fatal, and thus patients often have a long survival, but one that is characterized by periods of disease relapse and remission. The management of disease relapse typically consists of chemotherapy. The introduction of molecular targetted anticancer therapy has revolutionized the treatment of various tumors. In the case of lymphomas, the anti-CD20 agent rituximab plays a major role. The main study question here is whether induction chemotherapy and rituximab can improve the progression-free survival (PFS) compared to chemotherapy alone in patients with advanced indolent lymphoma (AIL). Of note, the authors initially intended to also compare the effects of CF (cyclophosphamide, fludarabine) vs. CVP (cyclophosphamide, vincristine, prednisone) chemotherapy on outcome. However, the CF arm was terminated secondary to unaccpetable toxicity (32 deaths vs. 8 in the CVP arm). The results reported here are for only those patients studied after discontinutaion of the CF arm.
Materials and Methods
The results of this trial establish the efficacy of CVP chemotherapy in achieving complete or partial remissions or disease stabilization in patients with advanced relapsed IL. The randomization analyzed here also supports the post-chemotherapy administration of at least 2 years of maintenance rituximab therapy in those patients achieving good response to induction chemotherapy. Furthermore, this benefit of additional maintenance treatment compared to observation appears to hold even in patients with follicular histology, high tumor burdens, and minimal residual disease post-chemotherapy.
While the results presented here are very promising, it is important to remember that this trial has relatively short follow-up, and for a disease with a long natural history, does not suffice to make far reaching conclusions. The long-term effect of the maintenance therapy on relapse rates "down the road" remains to be seen with longer follow-up of these patients. A second point to bear in mind is whether it would be preferable and reasonable to reserve rituximab for time of relapse, rather than providing it as maintenance, particularly in those with a complete response to chemotherapy. The authors feel, however, that the benefit of rituximab seen even in patients with minimal residual disease supports its use as maintenance.
Future studies might evaluate the use of induction chemotherapy and rituximab rather than induction chemotherapy alone, thus providing the benefits of rituximab to the whole group. Those patients could then later be randomized to additonal, maintenance rituximab versus no further treatment, in order to truly determine if rituximab provides beneift as a preventive agent, above and beyond its use as initial therapy.
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