Use of Bendamustine Combined with Rituximab in Chronic Lymphocytic Leukemia Patients: A Single Center Experience

Abstract

Background:There is no single standard treatment (tx) modality for symptomatic chronic lymphocytic leukemia (CLL) patients (pts). Fludarabine, cyclophosphamide, and rituximab (FCR) is the prefered regimen for healthy, young pts (<65 years). However, through the disease course almost all pts in this group will relapse and may become refractory to fludarabine-containing regimens. Additionally, for older adults (>65 years) and pts with comorbidities fludarabine is not a suitable agent. Bendamustine combined with rituximab (BR) is an acceptable alternative in these patient groups.Aim: To evaluate the efficacy and safety of BR in previously untreated or relapsed/refractory (R/R) CLL pts.Patients and Methods: Ptswho received BR as first- or further lines of tx were enrolled in the study. Data were analysed as of August 2017. The standard dose of bendamustine was 70 mg/m2 in D1 and D2 for R/R pts and 90 mg/m2 in D1 and D2 for tx naive pts. Rituximab dose was 375 mg/m2 in the first cycle and 500 mg/m2 in consecutive cycles. Pts' demographics, disease stages, biological and cytogenetic prognostic markers, comorbidities, previous treatments, bendamustine dose, cycle durations, use of G-CSF, adverse events (AEs), tx responses and follow-up periods were noted retrospectively. Evaluation of response was established according to NCI-WG guidelines [Hallek et al, 2008]. All toxicities were assessed according to the National Cancer Institute's Common Toxicity Criteria (NCI-CTC), version 4.Results: Nineteen ptswere enrolled in the study (Table 1). Thirteen pts were male and the median age at the time of BR treatment was 61 years (range, 41-80 years), with 9 pts (47%) older than 65 years. At the time of diagnosis, 7 pts (37%) were Rai stage IV. Del(13q), del(11q), and del(17p) were positive in 5, 1, and 2 pts, respectively. All pts had active disease as defined by the NCI-WG. Five pts received BR as first-line. Of the previously treated 14 pts, 71% had received fludarabine with either alkylating agents and/or rituximab. Median number of previous lines of tx was 2.Among comorbidities, hypertension (32%), asthma/COPD (32%) and type 2 diabetes mellitus (3%) were the three most common.Bendamustine dose ranged from 70 mg to 100 mg/m2. According to the physicians' decision, bendamustine was started as 70 mg in first cycle of tx and was escalated to the planned dose in all pts but three. All 6 intended courses were administered to 15 pts (79%), and in the remaining 4 pts, 3 died due to infections and one patient required early discontinuation due to prolonged neutropenia. In 8 pts (42%) tx cycle prolonged to 35 days and in 11 cases (58%) G-CSF were used during tx.After a median follow-up of 17 months (mos), five of 19 pts (26%) had progressed at the time of analysis, and median time to next treatment (TTNT) was 12 mos (range, 5-34 mos). Treatment responses are shown in Table 2. During the follow-up 5 pts (26%) died. Two had multiple comorbidities, three received bendamustine doses ≥90 mg/m2. Deaths were due to R/R disease and/or infections. Median OS after treatment was 13 mos (range, 5-34 mos).Overall, grade III-IV AEs occurred in 14 cases (74%): the most common toxicity was hematologic AEs (anemia in 2, neutropenia in 12, and thrombocytopenia in 2 cases), and serious infection occurred in six pts (2 bacterial pneumonia, 4 neutropenic fever). Non-hematologic toxicities were grade II rash in one, and grade II nausea in one patient.Conclusion: BR is effective and safe in treatment naive CLL patients and shows notable activity in R/R pts. Major toxic effect are myelosuppresion and infections. Higher doses of bendamustine should be avoided in patients with comorbidities and older age. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.