Efficacy of bendamustine and rituximab in unfit patients with previously untreated chronic lymphocytic leukemia. Indirect comparison with ibrutinib in a real‐world setting. A GIMEMA‐ERIC and US study

Abstract

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Real Life Use of Bendamustine in Elderly Patients with Lymphoid Neoplasia

“…Results from these studies yielded median PFS values of about 40–43 months in patients receiving BR as frontline treatment [ 5 , 12 ], but only 11 months (4-year PFS: 4.6%) in subsequent lines of therapy [ 4 , 28 ]. Real-life multicentric experiences observed similar, if not slightly better results (median PFS: 45 months in previously untreated CLL, and 25 months in relapsed CLL) [ 6 , 7 , 29 ] and reflected a good efficacy even for advanced-age patients, showing no difference in clinical responses between 60 and 80 years of age [ 30 ].…”

“…Similarly, a matched-adjusted indirect comparison of patients who had received BR or ibrutinib as first salvage treatment outside of clinical trials showed no OS difference [ 6 ]. More recently, a retrospective study has demonstrated that BR is an effective first-line regimen in unfit patients (largely consisting of elderly patients aged > 65 years), with the exception of patients with unfavorable genetic features (i.e., del(17p)/TP53 aberrations and IGHV-unmutated status) [ 7 ]. However, the safety and efficacy of bendamustine-containing regimens according to age groups of patients with CLL is so far unexplored.…”

“…Bendamustine is usually regarded as a tolerable regimen, less toxic compared to other classical chemotherapy combinations; evidence from clinical trials report that the most common grade 3–4 toxicity events related to bendamustine are nausea, vomiting, skin rash, fatigue, myelosuppression and infections [ 7 , 8 , 9 , 12 ]. Recent systematic reviews showed that incidence of such events with bendamustine was not significantly superior than with R-CHOP, chlorambucil or rituximab-fludarabine, and cyclophosphamide (R-FC) regimens [ 13 , 14 ]; however, special interest has been raised on the incidence of infections in bendamustine-exposed patients, particularly for atypical agents like cytomegalovirus (CMV) and Pneumocystis Jirovecii (PJ) [ 15 , 16 , 17 , 18 ].…”

Low‐dose fludarabine and cyclophosphamide combined with rituximab in the first‐line treatment of elderly/comorbid patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL): long‐term results of project Q‐lite by the Czech CLL Study Group

“…The main patient characteristics (median age 70 years; median CIRS score 5, median creatinine clearance 69 ml/min) demonstrate that patients in our present cohort were older and more comorbid than in the trials specifically designed for younger, fit patients [e.g. CLL10 trial: median age in the FCR and bendamustine and rituximab (BR) arms: 62 vs. 61 years, median CIRS score 2 vs. 2, median creatinine clearance 87 vs. 86 ml/min]; 4 on the other hand, published results of trials using chlorambucila and obinutuzumab indicated significantly older and somewhat principal data on studies using LDFCR [26][27][28][29] or BR 23,[30][31][32] regimens in untreated CLL. Interestingly, the median PFS of patients with mutated IGHV in BR arms of the CLL10 (56 months) 4 and the Alliance trial (51 months) 23 are comparable to our present result of 53 months; importantly, there was no significant difference between the ibrutinib arms and the BR arm regarding PFS in patients with mutated IGHV in the Alliance study.…”

“…There are five other publications on dose‐reduced FCR in the first‐line therapy of CLL; in addition, given the patient population in the present study, it seems logical to compare the results with the BR regimen as the patient cohorts in publications on BR, as well as the efficacy and safety data, are closest to our present results on LDFCR. Table V summarises the principal data on studies using LDFCR 26–29 or BR 23,30–32 regimens in untreated CLL. Interestingly, the median PFS of patients with mutated IGHV in BR arms of the CLL10 (56 months) 4 and the Alliance trial (51 months) 23 are comparable to our present result of 53 months; importantly, there was no significant difference between the ibrutinib arms and the BR arm regarding PFS in patients with mutated IGHV in the Alliance study 23 .…”