Intervention Review

Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin's lymphoma

  1. Holger Schulz1,*,
  2. Julia Bohlius1,
  3. Nicole Skoetz1,
  4. Sven Trelle2,
  5. Thilo Kober3,
  6. Marcel Reiser4,
  7. Martin Dreyling5,
  8. Michael Herold6,
  9. Guido Schwarzer7,
  10. Michael Hallek4,
  11. Andreas Engert1

Editorial Group: Cochrane Haematological Malignancies Group

Published Online: 17 OCT 2007

Assessed as up-to-date: 21 AUG 2007

DOI: 10.1002/14651858.CD003805.pub2


How to Cite

Schulz H, Bohlius J, Skoetz N, Trelle S, Kober T, Reiser M, Dreyling M, Herold M, Schwarzer G, Hallek M, Engert A. Chemotherapy plus Rituximab versus chemotherapy alone for B-cell non-Hodgkin's lymphoma. Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No.: CD003805. DOI: 10.1002/14651858.CD003805.pub2.

Author Information

  1. 1

    University Hospital of Cologne, Cochrane Haematological Malignancies Group, Department I of Internal Medicine, Cologne, Germany

  2. 2

    University of Bern, Division of Clinical Epidemiology and Biostatistics, Institute of Social and Preventive Medicine, Bern, Switzerland

  3. 3

    Smiling Press Productions, Scullin, Australia

  4. 4

    University Hospital of Cologne, Department I of Internal Medicine, Center of Integrated Oncology Köln Bonn, Cologne, Germany

  5. 5

    Klinikum der Universität München-Großhadern, Medizinische Klinik III, München, Germany

  6. 6

    2. Medizinische Klinik, Helios Klinikum Erfurt, Medical Clinic Hematology/Oncology, Erfurt, Germany

  7. 7

    German Cochrane Center, Department of Medical Biometry and Statistics, Freiburg, Germany

*Holger Schulz, Cochrane Haematological Malignancies Group, Department I of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, Cologne, 50924, Germany. hschulz@pioh.de.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 17 OCT 2007

SEARCH

 

Abstract

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

Background

Rituximab (R) has been shown to improve response rates and progression free survival when added to chemotherapy in patients with indolent and mantle cell lymphoma. However, the impact of R on overall survival (OS) when given in combination with chemotherapy (R-chemo) has remained unclear so far.

Objectives

We thus performed a comprehensive systematic review in this group of patients to compare R-chemo with chemotherapy alone with respect to OS. Other endpoints were overall response rate (ORR), toxicity and disease control as assessed by measures such as time to treatment failure (TTF), event free-survival (EFS), progression free-survival (PFS) and time to progression (TTP).

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and conference proceeding from 1990 to 2005.

Selection criteria

Only randomised controlled trials (RCT) comparing R-chemo with chemotherapy alone in patients with newly diagnosed or relapsed indolent lymphoma and mantle cell lymphoma (MCL) were included.

Data collection and analysis

Two review authors extracted data and assessed the study quality. Number needed to treat (NNT) were calculated to facilitate interpretation.

Main results

Seven randomised controlled trials involving 1943 patients with follicular lymphoma, mantle cell lymphoma, or other indolent lymphomas were included in the meta-analysis. Five studies were published as full-text articles, and two were in abstract form. Patients treated with R-chemo had better overall survival (hazard ratio [HR] for mortality 0.65; 95% confidence interval (CI) 0.54 to 0.78), overall response (relative risk of tumour response 1.21; 95% CI 1.16 to 1.27), and disease control (HR of disease event 0.62; 95% CI 0.55 to 0.71) than patients treated with chemotherapy alone. R-chemo improved overall survival in patients with follicular lymphoma (HR for mortality 0.63; 95% CI 0.51 to 0.79) and in patients with mantle cell lymphoma (HR for mortality 0.60; 95% CI 0.37 to 0.98). However, in the latter case, there was heterogeneity among the trials (P 0.07), making the survival benefit less reliable.

Authors' conclusions

The systematic review demonstrated improved OS for patients with indolent lymphoma, particularly in the subgroups of follicular and in mantle cell lymphoma when treated with R-chemo compared to chemotherapy alone.

 

Plain language summary

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

Although the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy (R-chemo) has been shown to improve response rates and progression-free survival in patients with indolent or mantle cell lymphoma, the efficacy of R-chemo with respect to overall survival is unclear.

Study design: Meta-analysis of seven randomised controlled trials involving 1943 patients.
Contribution: Patients treated with R-chemo had better overall survival, overall response, complete response, and disease control but more leukocytopenia and fever than patients treated with chemotherapy alone. R-chemo improved overall survival in patients with follicular lymphoma. Implications: Concomitant treatment with rituximab and standard chemotherapy regimens should be considered the standard of care for patients with indolent and mantle cell lymphomas who require therapy and for patients with follicular lymphoma.
Limitations: Heterogeneity among the analysed mantle cell lymphoma trials precluded reliable assessment of efficacy of R-chemo with respect to overall survival. Variability in treatment regimens among trials precluded determination of which chemotherapy regimen is the best to combine with rituximab or about the optimal number of cycles needed to treat patients with indolent lymphoma.
Future directions: From our view future studies should focus on the following points:
1. Which standard chemotherapy should be used in combination with Rituximab
2. Influence of clinical and biologic prognostic markers after R-chemotherapy. What is similar and what is different
3. Understanding rituximab efficacy and resistance
4. Role of rituximab in treatment of progressive disease
5. Mechanism of rituximab in combination with chemotherapy
6. Role of Pharmacokinetic, pharmacogenetics in the treatment with R-chemo
7. Role of subsequent therapy with rituximab after R-chemo

 

摘要

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

背景

比較化學治療合併Rituximab或單獨化學治療用於B細胞非何杰金氏淋巴癌

目前已知在進展緩慢(indolent)和套膜細胞淋巴瘤(mantle cell lymphoma)使用化學治療加上rituximab(R)可以改善反應率和無惡化存活率(progression free survival)。然而R合併化學治療(Rchemo)對整體存活率(OS)的影響至今仍未明。

目標

因此我們在這群病患進行完整的系統回顧,比較R化學治療和單獨用化學治療對整體存活率的影響。其他研究滿足點(endpoint)包括整體反應率(ORR),毒性及以各種測量如到達治療失敗時程(TTF),無事件存活率(EFS),無惡化存活率(PFS)及到達惡化時程(TTP)來評估疾病控制率。

搜尋策略

我們搜尋考科藍臨床試驗註冊目錄(CENTRAL) (考科藍圖書館),MEDLINE,EMBASE和從1990年到2005年進行的會議。

選擇標準

只有包含那些在新診斷或復發的進展緩慢淋巴癌及套膜細胞淋巴癌(MCL)比較使用R合併化學治療和單獨化學治療的隨機對照試驗(RCT)。

資料收集與分析

兩位審查作者收集資料並評估研究品質。同時計算益一需治數(number need to treat,NNT)來幫助資料解讀。

主要結論

統合分析(metaanalysis)共包含七個隨機對照試驗,共有1943位濾泡淋巴癌(follicular lymphoma),套膜細胞淋巴癌或其他進展緩慢的淋巴癌病患。其中有五個試驗為全文出版,另外兩個是摘要形式。比起單獨接受化學治療的病患,接受R合併化學治療的病患有較佳的整體存活率(HR 0.65; 95% CI 0.54 – 0.78),整體反應率(RR 1.21; 95% CI 1.16 – 1.27)和疾病控制率(HR 0.62; 95% CI 0.55 – 0.71)。R合併化學治療可以改善濾泡淋巴癌病患(HR 0.63; 95% CI 0.51 – 0.79)和套膜細胞淋巴癌病患(HR 0.60; 95% CI 0.37 – 0.98)的整體存活率。然而後者在試驗中較具異質性(heterogeneity),這使得它的存活益處較不可靠。

作者結論

這個系統回顧指出在進展緩慢的淋巴癌病患,尤其是濾泡淋巴癌和套膜細胞淋巴癌族群,使用R合併化學治療相較於單獨化學治療可以改善整體存活率。

翻譯人

本摘要由慈濟醫院黃冠博翻譯。

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

總結

雖然目前已知在進展緩慢淋巴癌和套膜細胞淋巴癌病患,化學治療併用抗CD20單株抗體rituximab (Rchemo)可以改善反應率和無惡化存活率。但是R併用化學治療對整體存活率的療效仍未知。研究設計:統合分析包含七個隨機對照試驗,共有1943位病患。 貢獻:接受R併用化學治療的病患有較佳的整體存活率,整體反應率,完全反應率(complete response)及疾病控制率。但是比起那些單獨接受化學治療的病患,他們有較多的白血球低下和發燒機率。R併用化學治療用在濾泡淋巴癌病患可以改善整體存活率。應用:對於需要接受治療的進展緩慢淋巴癌和套膜細胞淋巴癌病患,以及濾泡淋巴癌病患,應該考慮化學治療配方同時併用rituximab為標準治療方式。限制:因為分析試驗中套膜細胞淋巴癌的異質性,使得評估R併用化學治療對整體存活率的療效變得不可靠。針對進展緩慢淋巴癌病患在不同試驗中治療配方的變異性,使我們無法決定需用何種化療配方來合併rituximab治療是最佳選擇,也很難決定最適當的療程數目。未來方向:我們認為未來的研究應針對下列議題:1.需用何種標準化學治療來和rituximab併用 2.使用R合併化學治療後影響臨床和生物預後的因子。有何相同或不同之處3.瞭解rituximab的療效和抗藥性4.在疾病惡化時rituximab的治療角色 5.化學治療合併rituximab的機轉 6.藥物動力學(pharmacokinetic)和藥物基因學(pharmacogenetics)在R合併化學治療時的角色7. R合併化學治療後接續rituximab治療的角色