Pharmaceutical follow-up for patients on rituximab therapy for non-Hodgkin lymphoma: what is the evidence?

BACKGROUND: Introduction of the monoclonal antibody rituximab to chemotherapy regimens has substantially improved disease-free and overall survival in patients with non-Hodgkin lymphomas (NHL). The short-term safety of this drug has been widely reported, but there are few data on long-term safety, which suggests that these patients require prolonged follow-up. AIM OF THE REVIEW: To review the literature on follow-up models, with a focus on the safety of rituximab therapy for diffuse large B-cell lymphoma and follicular lymphoma. METHOD: The Cochrane Library, Embassy, Lilacs, Medline, and Scirus databases were searched for systematic reviews and randomized controlled trials. Furthermore, textbooks and journals on pharmaceutical care and institutional websites were searched for patient management recommendations. The outcomes were follow-up models and grade 3, 4, and 5 adverse reactions. RESULTS: Five systematic reviews and eight clinical trials or updates describing patient follow-up or reporting adverse reactions were identified. Only one systematic review and seven clinical trials reported follow-up routines for patients receiving rituximab, including information on staging, frequency of reassessment, and laboratory tests, as well as pre-infusion care and management of acute or delayed adverse reactions. Five systematic reviews and four clinical trials reported data on statistically significant adverse reactions (fever, leukopenia, infection). Four guidelines or institutional protocols for treatment and follow-up were identified, as well as seven studies describing experiences in the implementation of pharmaceutical care for oncology patients, but none were specifically focused on follow-up of patients receiving rituximab for NHL. CONCLUSION: Although some systematic reviews and clinical trials contain guidance on follow-up of patients receiving rituximab for NHL, there are no validated strategies for systematic follow-up of these patients with a focus on safety. As there are few data on long-term safety profile of these novel treatments, monitoring strategies should be developed and implemented to ensure safe and optimized use of drugs recently added to the therapeutic arsenal of clinical oncology.

Follow-up of patients receiving rituximab for diffuse large B cell lymphoma: an overview of systematic reviews.

The advent of rituximab has significantly improved the clinical outcomes of patients with diffuse large B cell lymphoma (DLBCL). Although rituximab is considered safe and effective, data on its long-term use are limited, which suggests that patients should undergo systematic, long-term follow-up aiming to identify delayed or yet undescribed adverse reactions and optimize treatment effectiveness. This study presents an overview of systematic reviews of strategies for follow-up of DLBCL patients receiving rituximab and documents the current state of knowledge on efficacy and safety in this population. A highly sensitive strategy was used to identify systematic reviews of randomized clinical trials (RCTs) in the Cochrane Library, Embase, Lilacs, MEDLINE, and Scirus databases. A handsearch of medical and government agency websites was also conducted. Seven studies were included, among them there were RCTs of patients who used CHOP/CHOP-like chemotherapy plus rituximab for three to eight cycles every 14 to 21 days as induction therapy, whereas some studies used maintenance therapy for 3 to 24 months. Only one study described a follow-up model for management of adverse drug reactions. The benefits of rituximab for induction therapy of DLBCL were demonstrated, although there is no evidence of significant improvement in the overall survival of high-risk patients or those with HIV-related lymphoma. Rituximab therapy was associated with increased rates of fever, infection, and grade 3/4 hematological toxicity, as well as higher infection-related mortality in HIV-positive patients. Although one study addressed the management of adverse reactions to rituximab, our search did not yield any publications on systematic follow-up strategies for these patients. This finding suggests that such instruments should be developed and validated to optimize the effectiveness and long-term safety of novel therapies.