Effectiveness of the Combination of Rituximab and Standard Chemotherapeutic Regimens in Previously Untreated Patients with Chronic Lymphocytic Leukaemia in Real-Life: Results from a Noninterventional Study (CILI Study)

Róbert Szász,György Ujj,Katalin Pál,Tamás Schneider,Elvira Altai,Péter Dombi,Natália Jóni,János Iványi,Péter Farkas,János Jakucs,Árpád Illés,Klára Piukovics,Ilona Tárkányi,Ágnes Nagy,Zsolt Nagy,László Szerafin

doi:10.1007/s12253-018-0474-9

Abstract

Chronic lymphocytic leukemia (CLL) is one of the most common haematological malignancies exhibiting remarkable heterogeneity in clinical course. Rituximab added to standard chemotherapy has been proven to increase response rate and eventually survival among previously untreated CLL patients. CILI was an open-label, non-randomized, single arm, multicentric, observational study aimed to collect real-life effectiveness data for rituximab used according to the current label in combination with standard chemotherapy in previously untreated CLL patients. Overall response rates (ORR) in the entire study population as well as in various subgroups were estimated. Adverse events were recorded during the entire course of the study. A total number of 150 patients were enrolled by 15 Hungarian study sites. Out of these, 82 patients received 6 cycles of rituximab containing treatment. Overall response rates of 88.24% (CI95%: 81.6–93.12%) and 94.59% (CI95%: 86.73–98.51%) were recorded in the intent-to-treat (ITT) and per-protocol (PP) populations, respectively. In both study populations, somewhat higher ORR was observed in patients aged ≥65 years. Subgroups defined according to either chromosomal aberrations (presence of 11q and 17p deletions) showed apparently high ORRs, though these rates were most probably biased by low patient numbers. 144 adverse events were reported during the study, of which 15 AEs were considered to be related to the administration of rituximab. Analyses of the efficacy variables have revealed comparable results to those previously reported by controlled clinical trials.

Highlights

Chronic lymphocytic leukemia (CLL) is a malignant lymphoproliferative disease characterized by uncontrolled replication of B-lymphocytes
Anti-CD20 therapy in combination with chlorambucil is recommended for patients with significant comorbidities and rituximab plus bendamustin for older fit patients [19, 20]
According to the current label, rituximab 375 mg/m2 body surface area administered on day 0 of the first treatment cycle followed by 500 mg/m2 body surface area administered on day 1 of each subsequent cycle

Summary

Introduction

Chronic lymphocytic leukemia (CLL) is a malignant lymphoproliferative disease characterized by uncontrolled replication of B-lymphocytes. CLL is the most common subtype of leukemia in the Western world with an incidence of 4.2 cases per 100,000 persons per year [1]. CLL affects mostly elderly patients; the median age at the time of diagnosis was reported to be 70 years. Since 5%– 10% of the patients with CLL have a family history of lymphoid malignancies [1]. CD19 positive CLL B-cells are characterized by the increased expression of CD5 and CD23 antigens and the low expression of CD20, CD79b, and surface immunoglobulin. Blood smear morphology typically shows mature lymphocytes and Gumprecht shadows [2]

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