5.45 Rituximab Infusion-Related Toxicity In Patients With CLL

Abstract

Background: Rituximab in combination with chemotherapy is an effective treatment of patients (pts) with chronic lymphocytic leukemia (CLL). The most frequent adverse event of rituximab is infusion–related toxicity, e.g. cytokine–release syndrome that occurs usually during the first infusion. However, there are scarce data on feasibility and tolerability of rituximab infusions in CLL outside clinical trials. Therefore, we performed a single–center retrospective analysis of the frequency of rituximab infusion–related adverse events during first– and second-line CLL treatment administered in routine practice. We also analyzed its relation to parameters of tumor load and possible association with treatment efficacy. Patients and Methods: We analyzed 87 pts (61 males, median age 63 years [range 32–83]) with CLL treated between March 2005 and March 2011 at our institution. The most common first-line regimens were FCR (36 pts) and low-dose FCR (13 pts); 5 pts were treated with other protocols. Thirty-three pts underwent second-line treatment: 16 pts FCR, 12 pts rituximab dexamethasone, 7 pts low-dose FCR and 8 pts other regimens. Intravenous hydration (2000 ml on days 0 and 1 of cycle), allopurinol 300–600 mg p.o. and premedication with methylprednisolone 80 mg i.v., acetaminophen 1000 mg p.o. and bisulepine 1 mg i.v. were administered before rituximab infusion. Rituximab was given by fractionated infusion (100 mg for 2 hours, then, if tolerated well, the rest of the dose with infusion rate escalation from 100 mg/hour up to 400 mg/hour) in a total dose 375 mg/m in the first cycle and 500 mg/m in subsequent cycles. Results: Rituximab infusion-related toxicity occurred in 33% of pts (n 18) during first-line treatment and 21% of pts (n 33) during second-line treatment. Adverse events were predominantly mild and the National Cancer Institute Common Terminology Criteria for Adverse Events grade III/IV occurred rarely (2% in the first line, 3% in the second line). Infusion toxicity manifested predominantly as rigors, chills, fever and/or hypotension and grade III/IV adverse events were syncope, respiratory distress and hypotension with collapse. All patients with adverse events could finish rituximab infusion at the initially planned dose on the same day. Treatment response analysis did not demonstrate statistically significant differences between patients with and without rituximab infusion toxicity (first line ORR 86% vs. 89%, second line 57% vs. 58%). Patients who developed rituximab infusion toxicity had higher initial absolute lymphocyte count (first line, 87 vs. 56 10/L, p 0.21; second line, 101 vs. 14 10/L, p 0.043). At the median time of follow up 16 months, there were no statistically significant differences in PFS or OS between cohorts. Conclusions: Rituximab infusion-related toxicity in pts with CLL is relatively frequent (33%). However, occurrence of infusion-related symptoms can be reduced by proper premedication and severe adverse events are uncommon. In our experience, all patients were able to receive the planned dose of rituximab. We did not find a statistically significant association between rituximab infusion toxicity and effectiveness of treatment. Acknowledgements: Supported by research project MZO 00179906 from Ministry of Health, Czech Republic.