Rituximab Plus Chlorambucil As First-Line Treatment for Chronic Lymphocytic Leukemia: Final Analysis of an Open-Label Phase II Study

Abstract

A B S T R A C T PurposeMost patients with chronic lymphocytic leukemia (CLL) are elderly and/or have comorbidities that may make them ineligible for fludarabine-based treatment. For this population, chlorambucil monotherapy is an appropriate therapeutic option; however, response rates with chlorambucil are low, and more effective treatments are needed. This trial was designed to assess how the addition of rituximab to chlorambucil (R-chlorambucil) would affect safety and efficacy in patients with CLL. Patients and MethodsPatients with first-line CLL were treated with rituximab (375 mg/m 2 on day 1, cycle one, and 500 mg/m 2 thereafter) plus chlorambucil (10 mg/m 2 /d all cycles; day 1 through 7) for six 28-day cycles. For patients not achieving complete response (CR), six additional cycles of chlorambucil alone could be administered. The primary end point of the study was safety. ResultsA total of 100 patients were treated with R-chlorambucil, with a median follow-up of 30 months. Median age of patients was 70 years (range, 43 to 86 years), with patients having a median of seven comorbidities. Hematologic toxicities accounted for most grade 3/4 adverse events reported, with neutropenia and lymphopenia both occurring in 41% of patients and leukopenia in 23%. Overall response rates were 84%, with CR achieved in 10% of patients. Median progression-free survival was 23.5 months; median overall survival was not reached. ConclusionThese results compare favorably with previously published results for chlorambucil monotherapy, suggesting that the addition of rituximab to chlorambucil may improve efficacy with no unexpected adverse events. R-chlorambucil may improve outcome for patients who are ineligible for fludarabine-based treatments.

Chlorambucil plus rituximab with or without maintenance rituximab as first‐line treatment for elderly chronic lymphocytic leukemia patients

“…The trial provided very satisfactory results: the response rate-82.4% OR, including 16.5% CR and 2.4% CRi, with cytometric MRD2 in 14% of CR cases-compares favorably with the 31-55% OR rates of trials using single-agent CLB at comparable doses [7,8,23], the 72% OR of the LRF CLL4 trial, using higher doses of single-agent CLB [6] and is supported by a similar British trial using CLB-R (OR 82%) [11]. Furthermore, in our study, PFS (34.7 months) is higher than that reported in trials using single-agent CLB (8.3-18 months) [6][7][8]12,23].…”

“…Infections occurred in 15.5% of patients, although rarely of grade 3-4 (1%). Thus, CLB-R toxicity compares favorably with other trials using CLB alone or with R [6][7][8]11,23]. Infusion-related side effects were limited.…”

“…Management of elderly patients has remained a primary unmet need until recently, when evidence-based therapeutic strategies exploring the association between CLB and anti-CD20 monoclonal antibodies are being reported [10][11][12].…”

A krónikus lymphocytás leukaemia korszerű molekuláris diagnosztikája és kezelése az új célzott terápiák korszakában

“…Korábban az idős betegek standard kezelése a chlorambucil-monoterápia volt. Fázis 2-es klinikai vizsgálatok bizonyították, hogy a chlorambucil-rituximab kombináció hatékonyabb a chlorambucil-monoterápiával szemben [45]. A chlorambucil és egyéb CD20-ellenes monoklonális antitest (ofatumumab vagy obinutuzumab) kombinációk hatékonyságát vizsgálták a COMPLEMENT és a CLL11-es klinikai vizsgálatokban [46,47].…”

Obinutuzumabe no tratamento de pacientes com leucemia linfoide crônica, não elegíveis à dose completa de fludarabina: análise de impacto orçamentário baseado no tempo para a próxima terapia

“…Apesar de eficaz, o FCR pode apresentar toxicidade excessiva, o que limita sua indicação ou a continuidade do tratamento, principalmente, em pacientes idosos (Eichhorst et al, 2009;Hallek et al, 2010). Apesar de alguns pacientes idosos serem elegíveis ao tratamento com FCR, muitos apresentam comorbidades, o que torna a associação FCR inapropriada para a maioria daqueles acima de 75 anos, que apresentam uma média de comorbidades de 4,2 para todos os tipos de câncer (Hillmen et al, 2014;Yancik, 1997). Esses pacientes são classificados como slow-go e o tratamento recomendado são as terapias anti-CD20 associadas a doses moderadas de clorambucila, sendo, assim, denominados pacientes slow-go (Hallek, 2015).…”