Intervention Review

Rituximab as maintenance therapy for patients with follicular lymphoma

  1. Liat Vidal1,*,
  2. Anat Gafter-Gvili2,
  3. Leonard Leibovici2,
  4. Ofer Shpilberg3

Editorial Group: Cochrane Haematological Malignancies Group

Published Online: 15 APR 2009

Assessed as up-to-date: 31 JAN 2009

DOI: 10.1002/14651858.CD006552.pub2


How to Cite

Vidal L, Gafter-Gvili A, Leibovici L, Shpilberg O. Rituximab as maintenance therapy for patients with follicular lymphoma. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD006552. DOI: 10.1002/14651858.CD006552.pub2.

Author Information

  1. 1

    Beilinson Campus, Rabin Medical Center, Department of Internal Medicine E, Petah-Tiqva, Israel

  2. 2

    Beilinson Campus, Rabin Medical Center, Department of Medicine E, Petah-Tiqva, Israel

  3. 3

    Rabin Medical Center, Institute of Hematology, Petah-Tikva, Israel

*Liat Vidal, Department of Internal Medicine E, Beilinson Campus, Rabin Medical Center, 39 Jabotinsky Street, Petah-Tiqva, 49100, Israel. vidall@clalit.org.il. vidallit@yahoo.com.

Publication History

  1. Publication Status: New
  2. Published Online: 15 APR 2009

SEARCH

 

Abstract

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Background

Rituximab, a monoclonal anti-CD20 antibody, in combination with chemotherapy improves overall survival compared to chemotherapy alone when used for induction therapy for patients with newly diagnosed or relapsed indolent lymphoma. Randomised controlled trials have demonstrated that maintenance treatment with rituximab prolongs progression-free survival but evidence of effect on overall survival is lacking.

Objectives

To evaluate the effects of maintenance treatment with rituximab on overall survival in patients with follicular lymphoma.

Search methods

We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 2), PubMed (June 2007), EMBASE (June 2007), LILACS (June 2007), databases of ongoing trials, and relevant conference proceedings. References of identified trials were searched and the first author of each included trial was contacted.

Selection criteria

Randomised controlled trials that compared rituximab maintenance therapy to observation, treatment at relapse (no maintenance therapy), or other maintenance treatment.

Data collection and analysis

Two authors independently appraised the quality of each trial and extracted data from included trials. Hazard ratios (HR) and relative risks with 95% confidence intervals (CI) were estimated and pooled using the fixed-effect model.

Main results

Five trials including 1056 adult patients were included in the review. Four trials (895 patients) were included in the analysis of overall survival. Patients treated with rituximab as maintenance therapy had a significantly better overall survival compared to observation alone (HR 0.53, 95% CI 0.38 to 0.73).

Authors' conclusions

Rituximab maintenance therapy should be added to standard therapy of patients with relapsed or refractory follicular lymphoma following a successful induction treatment. The drug should be given either as four weekly infusions every six months or as a single infusion every two to three months. Future randomised controlled trials should explore the effect of different protocols of rituximab maintenance therapy on overall survival.

 

Plain language summary

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

Rituximab as maintenance therapy for patients with follicular lymphoma

Follicular lymphoma is a B-cell lymphoma characterised by an initial response to treatment that is usually followed by relapse and progression. Most patients present with advanced disease that cannot be cured. Lymphoma B-cells express CD20. Rituximab, a monoclonal anti-CD20 antibody, is expected to be active against cells that express CD20. Compared to chemotherapy alone, rituximab in combination with chemotherapy improves overall survival when used for induction therapy (treatment designed as a first step toward reducing the number of cancer cells) for patients with newly diagnosed or relapsed indolent lymphoma. Clinical trials that have shown improved event-free survival were inconsistent regarding overall (all-cause) survival. We aimed to evaluate the effects of maintenance therapy with rituximab on overall survival in patients with follicular lymphoma.

Study design: systematic review and meta-analysis of five randomised controlled trials (1056 patients).
Contribution: patients with follicular lymphoma and high tumour burden treated with rituximab maintenance therapy had better overall survival and disease control but more infections than patients who were observed without rituximab.
Implications: rituximab maintenance therapy should be added to the standard therapy of patients with relapsed or refractory (to treatment) follicular lymphoma following a successful induction treatment.
Limitations: variability in treatment regimens among trials precluded determination of the optimal rituximab maintenance regimen. One trial compared rituximab maintenance to rituximab at disease progression for patients with lower tumour burden and found both options to be comparable.
Future research should focus on:
the effect of rituximab maintenance compared to rituximab at progression;
defining which patients benefit the most from rituximab, according to burden of disease, prognostic score, the type of chemotherapy regimens used for induction, and the inclusion of rituximab in induction; and
the optimal duration of maintenance treatment, as well as its schedule.
Both randomised controlled trials and observational trials should have longer follow up in order to assess the long-term toxicity of rituximab, and should evaluate quality of life outcomes.

 

摘要

  1. Top of page
  2. Abstract
  3. Plain language summary
  4. 摘要

背景

使用莫須瘤作為濾泡性淋巴瘤病人的維持治療

莫須瘤是一種抗CD20的單株抗體,與化學治療合併使用較單獨使用化學治療當使用於新診斷或是復發的惰性淋巴瘤,更能改善整體存活率。莫須瘤使用於維持治療在隨機控制試驗已證實可延長無病存活(prolongs progressionfree survival),但目前仍沒有證據顯示有整體存活的效果。

目標

目標:評估濾泡性淋巴瘤的病人使用莫須瘤作為維持治療對於整體存活的效果

搜尋策略

我們用電子搜尋Cochrane Central Register of Controlled Trials (CENTRAL) (考科藍實證醫學資料庫2007年第二期)、PubMed (2007六月)、醫藥學文獻資料庫(2007年六月)、LILACS (2007年六月),進行中臨床試驗的資料庫、相關會議的紀錄等。確定試驗的參考文獻都被收尋,並且聯繫各試驗的第一作者。

選擇標準

隨機控制試驗設計比較莫須瘤作為維持治療及觀察組,以及用莫須瘤作為復發治療(非維持性治療),或是其他維持性治療。

資料收集與分析

兩位作者分別評估各個試驗的品質,及從各試驗中擷取數據。危險比(Hazard ratio, HR)及相對危險性(Relative Risk, RR)的百分之九十五信賴區間利用固定效果模型(Fixed Effect Model)來評估收集。

主要結論

五個試驗共1056個成年病患包含在此檢閱中。其中有四個試驗(895個病人)包含在整體存活的分析中。使用莫須瘤作為維持性治療的病人比較於觀察組,有明顯較好的整體存活(危險比0.53, 百分之九十五信賴區間是0.38至0.73)。

作者結論

莫須瘤作為維持性治療須加入在濾泡性淋巴瘤經成功的引導性化療後復發,或頑治病人的標準治療內。藥物是每六個月一個療程,每週給一次連續四次,或是每二到三個月給單一次劑量。莫須瘤作為維持性治療,在不同的給法對於整體存活的評估,需進一步隨機控制試驗的驗證。

翻譯人

本摘要由慈濟醫院王柔云翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

濾泡性淋巴瘤是一種B細胞淋巴瘤,其特色在於給予初始治療後會發生疾病的復發及惡化。大多數的病患以重症且不能治癒為表現。淋巴瘤的B細胞有CD20的表現。莫須瘤是一個抗CD20的單株抗體,並且主動對抗表現CD20的細胞。與單用化學治療相比,莫須瘤在新診斷的淋巴瘤用於引導治療(為減少癌細胞數量的第一步)或是復發的惰性淋巴瘤,兩種情況合併化學治療可改善整體存活率。臨床試驗顯示無事件存活率(eventfree survival, EFS)的改善,和整體存活率是不一致的。我們評估莫須瘤在濾泡性淋巴瘤病人,用於維持治療的整體存活率。研究設計:系統性檢閱和多變數分析五個隨機控制試驗(1056人)。貢獻:濾泡性淋巴瘤和高腫瘤負荷者,使用莫須瘤作為維持治療,有較好的整體存活和疾病控制;但比較沒有使用莫須瘤的觀察組有較多的感染。應用:莫須瘤作為維持性治療須加入在濾泡性淋巴瘤經成功的引導性化療後,復發或頑治病人的標準治療內。限制:因各試驗間不同治療配方的變異性,導致無法取得莫須瘤作為維持治療的理想配方。其中一個試驗在低腫瘤負荷者,比較莫須瘤作為維持治療及莫須瘤在疾病惡化後使用的差異,他們發現兩個狀況是相當的。更進一步的研究需著重在,比較莫須瘤作為維持治療及在復發時使用的最大效益。依照腫瘤負荷的大小、預後分數、引導治療的化療配方、在引導化療時加入莫須瘤,以及維持治療給予時間的長短和時間表,去定義哪種病人使用莫須瘤可得到最大的益處。隨機控制試驗和觀察性試驗,需要長期的追蹤,以獲得莫須瘤的長期毒性,並且也要評估生活品質的結果。