This is the first study to provide evidence to support initiation of 90-minute rituximab infusion in rituximab-naïve patients. In this study, first and subsequent infusions of rituximab over 90 minutes can be safely administered in rituximab-naïve patients with hematologic malignancies. Additionally, this study is the first to include patients receiving Truxima, a biosimilar rituximab, in a rapid rituximab infusion protocol.
Safety and feasibility of 90-minute rituximab infusion have been evaluated in several studies, in which the low incidence of severe IRRs was observed3,5,13,14. Thus, accelerating the infusion rate of rituximab from the first cycle should not affect the safety profiles by reinforcing premedication before rituximab administration to reduce the risk and severity of IRRs. In the standard infusion method, any grade IRRs were reported in 77% of patients in the first cycle and 33% in the remaining cycles1. In the RATE trial, grade 3 or higher IRRs occur in 2.4% of patients during the first infusion at a standard infusion rate and in 1.1% of patients for the first rapid infusion6. Even though our patients did not receive the first dose of rituximab according to the standard titration scheme, the incidence of any grade or grade 3/4 IRRs during first rapid infusion (19.5% and 0.8%, respectively) was comparable to those of previous studies during first standard infusion, showing no increased IRRs in 90-minute infusion3,6,9. Most IRRs occurred during the first infusion, with a decreased incidence during second and subsequent infusions. The IRRs were generally resolved by temporary pause in the infusion and supportive care, consistent with previous studies2,3,5,6,14. In the present study, patients with older age (≥ 70 years) and high tumor burden, such as high disease stage and high LDH level, received 90-minute rituximab infusion without severe IRRs. Based on our findings, 90-min rituximab infusion from the first cycle of therapy is a feasible and tolerable treatment option for patients with hematologic malignancies. By decreasing the time, the patients need to spend in the infusion center, rapid rituximab infusion can mitigate an important obstacle to patient acceptance of rituximab therapy.
In many studies, premedication usually included acetaminophen and an antihistamine before each rituximab infusion to prevent or minimize serious adverse drug events, but the use of corticosteroid as a part of premedication varies widely2–6, 9. In the RATE study, corticosteroid (prednisone or prednisolone) was administered mandatorily prior to rituximab infusion, and only 1.1% of grade 3 IRRs was reported6. Similarly, Atay et al. reported a 2-year experience with 90-minute rituximab infusion in which 75 patients were recommended to receive daily corticosteroid prior to rituximab infusion, and no grade 3 or 4 IRRs were observed3. All patients included in the present study also received a corticosteroid (hydrocortisone) 30 minutes prior to each rituximab infusion. Even though there is some controversy about the role of corticosteroid for preventing or reducing the occurrence of IRRs, introduction of corticosteroid premedication might be an important factor that does not increase incidence of severe IRRs during first rituximab infusion over 90 minutes. Further studies are needed to provide evidence supporting the role of corticosteroid as a premedication in first rituximab infusion.
Truxima, a biosimilar rituximab, has been used for treatment of malignant and autoimmune diseases was shown to be equivalent to originator rituximab in terms of efficacy, safety, and immunogenicity, resulting in potential for significant cost saving10–12. In this study, the safety profiles of originator rituximab and Truxima were evaluated, with no significant differences identified between groups in term of IRRs. The incidence of IRRs during the first infusion among Truxima-treated patients was 24.3%, which is slightly higher than that in originator rituximab-treated patients (17.2%), though the difference was not significant. One explanation of this result could be the small sample size of the Truxima group. The incidence of any grade and ≥ 3 grade IRRs during the first cycle is similar to previous finding of Truxima treatment in patients with newly diagnosed DLBCL and FL (24.3% vs. 24% and 0% vs. 0%, respectively)10. Most IRRs following Truxima administration over 90 minutes were mild and manageable, usually observed in the first cycle of treatment. The severity and type of IRRs and treatment outcomes were similar between originator rituximab and Truxima during first and subsequent rapid infusions. Based on our study, safety profiles and efficacy of Truxima administration over 90 minutes were comparable to those of originator rituximab, suggesting that Truxima might replace originator rituximab in a rapid rituximab infusion setting, resulting in reduced time and financial burden for patients.
This study has potential limitations, mostly stemming from the retrospective design. First, some patients receiving rituximab did not meet the inclusion criteria owing to lack of complete information regarding rapid infusion. In addition, any delayed IRRs following rituximab administration in both groups were not evaluated because most patients were discharged after 24 hours of rituximab administration if there were no adverse events. Another limitation of our study is lack of direct comparison data with patients receiving standard duration infusions in our institution. However, our results on safety and tolerability compare favorable to previously reported data regarding 90-minute rituximab infusion. Despite these limitations, we believe that our retrospective study provides clinical findings in that it could be of practical evidence for physicians who consider a 90-min rituximab infusion in their treatment options for hematologic malignancies.
In conclusion, in our experience, rituximab infusion time of 90 minutes is feasible and well tolerated by patients when administered as the first and subsequent infusions in the course of therapy with corticosteroid premedication, allowing considerable saving of time and cost of the patients and potentially ameliorating their adherence to treatment. In terms of IRR, safety profiles of Truxima, a biosimilar rituximab, were comparable to that of originator rituximab, suggesting that Truxima might replace originator rituximab in a rapid infusion setting. In the future, a comparative, prospective clinical trial is warranted to confirm these findings.