A Canadian Perspective on the Safe Administration of Bendamustine and the Prevention and Management of Adverse Events

Abstract

Although bendamustine has been used to treat lymphoproliferative disorders for decades, it has only recently been approved for use in Canada. Thus, Canadian recommendations on the administration of bendamustine and the management of common adverse events (aes ) are needed. This article highlights effective management and assessment strategies recommended by Canadian nurses and pharmacists for the most common aes arising from the use of bendamustine in patients with chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma. Those strategies include administering bendamustine over 60 minutes instead of 30 minutes, administering pre-medications to control infusion-related reactions and nausea, hydrating patients to minimize fatigue, and using free-flowing saline at the closest port to prevent phlebitis.

An Open-Label Expanded-Access Trial of Bendamustine in Patients with Rituximab-Refractory Indolent Non-Hodgkin Lymphoma or Previously Untreated Chronic Lymphocytic Leukemia: BEND-ACT

“…Moreover, the incidence of neutropenia-the only grade 3 or 4 teae resulting in dose delay-was higher in patients on the 21-day cycle (25%) than in those on the 28-day cycle (6.9%). Taken together, those results might provide support for use of the 28-day treatment cycle, which is routine with bendamustine in many treatment centres across Canada for the management of inhl 37 .…”

“…A paper by Koolwine et al 37 suggested that a shorter bendamustine infusion time might increase peak plasma levels, resulting in more frequent nausea. The authors recommended giving bendamustine to all patients in a 60-minute infusion.…”

“…Other anti-emetic therapies, including dexamethasone and prochlorperazine, were also frequently used. Bendamustine has a moderate emetogenic risk, and consequently, administration of a 5-HT 3 antagonist such as ondansetron 1-2 days before, during, and after bendamustine treatment is recommended 37,38 . To improve the anti-emetic effect and to prevent infusion and skin reactions, dexamethasone can also be given in combination with 5-HT 3 antagonists 30 minutes before bendamustine infusion 39 .…”

“…However, it is important to note that aprepitant is reimbursed only for the prevention of nausea and vomiting from highly emetogenic cancer chemotherapy, and consequently, its use in Canada might be limited 36,38,39 . Acetaminophen, which was used as supportive therapy in 27.8% of patients overall, is also suggested before infusion in patients who have previously experienced grade 1 or 2 infusion reactions (for example, fever, chills, rash) 37,38 .…”

Estimating the Burden of Illness of Relapsed Follicular Lymphoma and Marginal Zone Lymphoma in Ontario, Canada

“…Intravenous rituximab in combination with CVP was only approved for use as first-line therapy in the treatment of NHL by Health Canada on 20 December 2005 and as maintenance treatment on 28 July 2006, part way through the study period. Bendamustine in combination with rituximab received a Health Canada notice of compliance for use in the relapsed setting in August 2012 and public reimbursement in Ontario in May 2013 and then moved into use in the first-line setting [29]. In 2018, a subcutaneous preparation of rituximab was approved as a fixed dose for combination therapy, simplifying administration and reducing systemic therapy suite time [8], with a corresponding reduction in costs related to administration.…”