May 2013, Vol 4 No 3
Safety of Bendamustine in Treatment of CLL and NHLUncategorized
Chronic Lymphocytic Leukemia
Bendamustine is approved for single-agent use in chronic lymphocytic leukemia (CLL) based on the result from a phase 3 trial comparing bendamustine and chlorambucil.1 Progression-free survival was 18 months in the bendamustine group versus 6 months in the chlorambucil group. Bendamustine 100 mg/m2 was administered on days 1 and 2 of a 28-day cycle.1 Overall, bendamustine was well tolerated. The most common hematologic adverse events reported were anemia (89%), thrombocytopenia (77%), and neutropenia (75%). Laboratory values should be monitored on a weekly basis. Hematologic nadir typically occurs during week 3 of treatment. Blood transfusions were required in 20% of patients in the bendamustine arm versus 6% in the chlorambucil arm.1
The most common gastrointestinal adverse events included nausea (20%), vomiting (16%), diarrhea (9%), and weight loss (7%). Other nonhematologic adverse events included drug-related fever (24%), fatigue (9%), asthenia (8%), rash (8%), hyperuricemia (7%), nasopharyngitis (7%), chills (6%), hypersensitivity reactions (5%), pruritus (5%), and herpes simplex (3%).1
Adverse reactions and hypersensitivity reactions after the first infusion have been reported. Premedications such as antiemetics and steroids are given prior to infusions. Prophylaxis with antifungal, antiviral, and antibiotic therapy during treatment will help to prevent the possibility of fungal and herpes infections and pneumocystis pneumonia.
Dose reduction perimeters for grade 3/4 hematologic or nonhematologic adverse events are as follows: for the first occurrence, decrease the dose from 100 mg/m2 to 50 mg/m2. If the adverse events require a treatment delay, the same guidelines pertain and treatment is held until resolution of the grade 3/4 adverse event. If a second dose reduction is required, 25 mg/m2 would be given.1
Bendamustine is also approved as a single-agent therapy for patients with non-Hodgkin lymphoma (NHL) in whom rituximab or a rituximab-containing regimen has failed during or within 6 months of treatment.1 Safety results are from a single-agent therapy trial of 100 participants that produced a 74% overall response rate and median response of 9.2 months. The recommended dose of bendamustine for the treatment of NHL is 120 mg/m2 administered on days 1 and 2 of a 21-day cycle. Hematologic nadir is usually seen during week 3 of treatment, and weekly laboratory surveillance is recommended.1
In a study by Cheson and colleagues, growth factors or blood products were used in 31% of 903 cycles; growth factor alone was used in 51% of patients.2 Growth factor should be given after an episode of febrile neutropenia, not as prophylaxis.
The most common nonhematologic adverse events reported are nausea (75%), fatigue (57%), vomiting (40%), diarrhea (37%), pyrexia (34%), constipation (29%), weight loss (18%), stomatitis (15%), herpes zoster (10%), and urinary tract infection (10%).1 Grade 3/4 adverse events were more common in patients aged ?66 years than in younger patients (88% vs 66%, respectively).2 Protection from infection required placing the patient on antibacterial, antifungal, and antiviral prophylactic therapy. If dose reduction or dose delays for grade 3/4 adverse events is necessary, decrease the dose from 120 mg/m2 to 90 mg/m2 on days 1 and 2. If treatment delays or recurring grade 3/4 adverse events continue, the dose should be reduced to 60 mg/m2 on days 1 and 2.1
Overall, bendamustine is effective and generally well tolerated in patients with CLL and NHL. With diligent surveillance, side effect management, and patient education about the most commonly seen side effects, patients can receive documented benefit from bendamustine, with longer disease-free survival.
1. Trenda [package insert]. Frazer, PA: Cephalon, Inc; 2012.
2. Cheson BD, Friedberg JW, Kahl, BS, et al. Bendamustine produces durable responses with an acceptable safety profile in patients with rituximab-refractory indolent non-Hodgkin lymphoma. Clin Lymphoma Myeloma Leuk. 2010;10:452-457.
This is the third article in a 4-part series on bendamustine. While the previous article discussed the efficacy of bendamustine for patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) in the registration studies cited in the US product labeling, this article discusses its safety.1 The next article in [ Read More ]
The previous articles have outlined the clinical outcomes of clinical trials evaluating bendamustine in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL). The third in the series of articles discusses the short-term toxicities of bendamustine from these clinical trials. Patients with CLL are always a challenge to treat due to [ Read More ]