Demographics, treatment patterns, safety, and real-world effectiveness in patients aged 70 years and over with chronic lymphocytic leukemia receiving bendamustine with or without rituximab: a retrospective study

Abstract

Objectives: Bendamustine is a unique cytotoxic agent active against various human malignancies, including chronic lymphocytic leukemia (CLL). In vitro studies suggest that cytotoxic activity of bendamustine on CLL-derived cells is synergized by rituximab. A retrospective chart review was conducted to characterize treatment-naïve outpatients and those with relapsed disease aged 70 years and over with CLL receiving bendamustine (with or without rituximab) and to evaluate real-world patterns of care, safety, and effectiveness. Methods: Using McKesson Specialty Care/US Oncology Network iKnowMed databases, 91 outpatients with at least two recorded visits and at least two cycles of bendamustine monotherapy or bendamustine-rituximab combination therapy were identified and included. Mean age at diagnosis and start of first therapy was 70.3 and 77.4 years respectively, and 63.7% of patients were men. Results: Observed overall response rate was 56.3% in pooled treatment-naïve patients [n = 9; complete response (CR) 18.8%; partial response (PR) 37.5%; nodular partial response (nPR) 0%] and 58.7% in pooled patients with relapsed disease (n = 44; CR 13.3%; PR 44.0%; nPR 1.3%). Median time to progressive disease has not been reached for the 16 treatment-naïve patients (median follow up 15.1 months), and was 18.4 months for those with relapsed disease (n = 73). No unexpected toxicities were observed. Overall rate of blood/bone marrow toxicities (all grades) was 40.7%; grade 3/4 rates were 18.8% in treatment-naïve patients and 25.3% in those with relapsed disease. Most frequent nonhematologic adverse events were fatigue and rash. Conclusion: In this retrospective chart review of 91 outpatients with CLL aged 70 years and over, bendamustine (with or without rituximab) was an effective therapeutic option with manageable toxicity.

CD69 expression potentially predicts response to bendamustine and its modulation by ibrutinib or idelalisib enhances cytotoxic effect in chronic lymphocytic leukemia

“…Bendamustine is a well-tolerated and less toxic agent that has emerged as a feasible therapy for elderly and non-fit CLL patients [ 11 ]. Several trials have shown its clinical efficacy in previously untreated and refractory CLL patients being the combination of bendamustine with rituximab one of the first-line treatments for elderly patients with CLL lacking 17p deletion [ 12 – 15 ]. Nowadays, in vitro results and ongoing clinical trials have explored the combination of bendamustine with new generation monoclonal antibodies [ 16 , 17 ] and novel targeted agents[ 18 – 22 ].…”

Therapeutic potential of new B cell-targeted agents in the treatment of elderly and unfit patients with chronic lymphocytic leukemia

“…A larger study is needed to confirm these promising findings. In a retrospective study in outpatients ≥70 years of age receiving bendamustine monotherapy versus rituximab + bendamustine, the overall response rate was 50 % versus 67 %, respectively, in treatment-naive patients and 45 % versus 64 % in relapsed/refractory patients, with no unexpected toxicities [ 19 ]. Results of a subgroup analysis of a phase 2 clinical trial suggest that rituximab in combination with pentostatin and cyclophosphamide is effective and tolerable in older (≥70 years) as well as younger patients [ 20 ].…”

Recent Advances in the Pathogenesis and Treatment of Chronic Lymphocytic Leukemia

“…In recent years a number of less toxic regimens were explored in elderly CLL patients or patients with co-morbidities. These include reduced-intensity FCR and combinations of chlorambucil or bendamustine with the anti-CD20 monoclonal antibodies (mAb) rituximab or obinituzumab [67][68][69][70][71][72][73]. These regimens showed improved tolerability, but efficacy appeared to be generally reduced when compared to FCR.…”