Rituximab, a monoclonal antibody targeting CD20 receptors widely used in the treatment of non-hodgkin lymphoma, is now being used in various indications, on and off-label. For five University Hospitals in Quebec, Canada, rituximab represents more than 10% of the total drug expenses. Pharmacy managers gave the Therapeutic Drug Management Program (TDMP – www.pgtm.qc.ca) the mandate to evaluate rituximab use in those centers.
The objectives of the study were to describe rituximab use for all indications in our hospitals and to review the utilization of rituximab in maintenance therapy for follicular lymphoma according to predefined criteria.
A review of pharmacy databases was performed to identify patients who received rituximab between April 1st 2008 and March 31st 2009. Every patient file containing rituximab was reviewed. Patients’ medical records were also reviewed for pathology and side effects. No sampling was performed.
At least one dose of rituximab was administered to 797 adult patients during the study period. Median age was 62. The most frequent indications were follicular lymphoma (36%) and diffuse large B-cell lymphoma (26%) followed by chronic lymphoid leukemia (CLL) (8%). Various off label indications, including idiopathic thrombocytopenic purpura, hemolytic anemia and Waldenstrom macroglobulinemia, represented 30% of our population. At the time of data analysis, 42% of patients were still treated with rituximab, 45% had finished their planned treatment and 6% had discontinued treatment because of adverse events or disease progression. Thirty-eight patients (4.8%) died during the study period. Rituximab was also used in 41 pediatric patients for various indications, mostly for nephrotic syndrome (27%). The evaluation of patients outcome for off-label indications could not be performed due to the complexity, variety and chronic courses of diseases treated. For the 232 patients receiving rituximab as maintenance therapy, only 76% of patients had follicular lymphoma. Of these, 53% received rituximab maintenance after first-line treatment with R-CVP and 19% after R-CHOP. Only one patient receiving maintenance treatment stopped therapy because of disease progression. No death was reported. Conformity to utilization criteria was excellent for dose and frequency (100% and 99%) but lower for duration and indication (87 % and 70%). Of note, 13% exceeded the planned two years treatment length and fourteen patients received maintenance therapy following induction chemotherapy for CLL.
Rituximab was used in various on and off label indications and utilization criteria should be developed and followed in each centers. Pharmacy and therapeutics committees should also request an annual summary of efficacy and security for the off-label indications. Almost a third of patients treated with maintenance rituximab did not receive it for follicular lymphoma. A review of the literature should be performed and recommendations be made for other indications for maintenance treatment.
Off Label Use: review of utilisation or rituximab: non hematologic indications.
Asterisk with author names denotes non-ASH members.