Rapid Infusion of Biosimilar Rituximab Safe, Well Tolerated

At the American Society of Hematology’s (ASH) 59th Annual Meeting and Exposition in Atlanta, Georgia, on December 10, 2017, researcher Raakhee Shah, MPharm, and team will present the results of a study that demonstrates that patients can be switched from reference rituximab (MabThera) to biosimilar rituximab (Truxima) without reverting to slower infusion rates.¹

Rituximab is a monoclonal antibody approved in the European Union and United States to treat non-Hodgkin’s lymphoma and chronic lymphocytic leukemia (as well as other indications), and can be associated with infusion-related reactions (IRRs). The incidence of IRRs is greatest with the first infusion and decreases significantly with subsequent infusions.

In order to reduce the risk of IRRs, manufacturers recommend that the first dose be gradually increased every 30 minutes in increments of 50mg per hour to a maximum rate of 400mg per hour. For subsequent infusions, the dose is gradually increased every 30 minutes in increments of 100 mg per hour, known as standard subsequent rate infusion. This means a typical rituximab infusion can take 4 to 6 hours.

If the first infusion is well tolerated, it has become common practice to administer subsequent rituximab doses as a “rapid infusion” over 90 minutes, where 20% of the dose is given over the first 30 minutes, with the remaining 80% over the following 60 minutes.

This study aimed to assess the safety of rapid infusion of biosimilar rituximab by reviewing infusion r

elated adverse events (AEs) that fall into three categories: patients switching from the reference product, MabThera, to the biosimilar (n = 78), patients with previous exposure to the reference product but who received their last dose over 6 months prior (n = 6), and rituximab-naïve patients, (n = 58), respectively.

In total, 142 patients received the biosimilar between May 22, 2017 and July 26, 2017. Infusion-related reactions were noted from nursing infusion records and graded using Common Terminology Criteria for Adverse Events, Version 4.03.

Patients who had been receiving the reference product as a rapid infusion continued at this rate with the biosimilar. Those patients who had only received 1 prior dose of the reference product at the standard first-dose infusion rate received their first dose of the biosimilar as a rapid infusion.

Patients who had not received the reference product for over 6 months or were rituximab-naïve received their first dose at the standard first dose infusion rate. If the first infusion was well-tolerated, subsequent doses were given as rapid infusion. All patients received premedication with acetaminophen and an antihistamine.

The results of the study showed that the rapid infusion of the biosimilar was well-tolerated in all 3 groups of patients. In addition, patients who switched from the reference safely received their first dose of the biosimilar as a rapid infusion. One patient who switched from the reference developed tachycardia during the first dose of the biosimilar at a rapid infusion rate; however, this patient was able to receive subsequent doses of the biosimilar with an added glucocorticoid pre-medication without further IRRs.

Grade 2 or 3 IRRs were observed with 8 first-rate infusions (12%) and 4 of the patients received further doses of the biosimilar. These patients received their next doses at the standard subsequent infusion rate with glucocorticoid pre-medication without incident, and 2 of the patients received further doses at a rapid infusion rate without an IRR. Researchers plan to present updated results during the ASH meeting.

This study is the first reported post-marketing experience of rapid infusion of biosimilar rituximab, and showed that patients can be safely switched from the reference product to rituximab biosimilar without reverting to slower infusion rates. The authors hope that these findings will facilitate the introduction of the biosimilar at centers prescribing rituximab without adversely impacting resource utilization or the patient experience.

Reference

1. Shah R, Cheesman S, Ardeshna K, et al. Evaluation of the safety and tolerability of rapid infusion of biosimilar rituximab Truxima-the University College London hospitals (UCLH) experience. Presented at the American Society of Hematology 59th Annual Meeting and Exposition 2017, December 10, 2017; Atlanta, GA. Abstract 3387. https://ash.confex.com/ash/2017/webprogram/Paper107375.html