Chlorambucil versus observation after anti-Helicobacter therapy in gastric MALT lymphomas: results of the international randomised LY03 trial

Barry W Hancock, Wendi Qian, David Linch, Jean-Charles Delchier, Paul Smith, Ira Jakupovic, Cathy Burton, Robert Souhami, Andrew Wotherspoon, Christiane Copie-Bergman, Carlo Capella, Catherine Traulle, Michael Levy, Sergio Cortelazzo, Andres J M Ferreri, Achille Ambrosetti, Graziella Pinotti, Giovanni Martinelli, Umberto Vitolo, Franco Cavalli, Christian Gisselbrecht, Emanuele Zucca, Barry W Hancock, Wendi Qian, David Linch, Jean-Charles Delchier, Paul Smith, Ira Jakupovic, Cathy Burton, Robert Souhami, Andrew Wotherspoon, Christiane Copie-Bergman, Carlo Capella, Catherine Traulle, Michael Levy, Sergio Cortelazzo, Andres J M Ferreri, Achille Ambrosetti, Graziella Pinotti, Giovanni Martinelli, Umberto Vitolo, Franco Cavalli, Christian Gisselbrecht, Emanuele Zucca

Abstract

Gastric mucosa-associated lymphoid tissue (MALT) lymphomas are uncommon tumours characterised by a tendency to remain localised for long periods. The aetiological association between MALT lymphomas and Helicobacter pylori is well established. The role of additional chemotherapy after H. pylori eradication in localised MALT lymphomas is unclear. The LY03 trial was designed to establish whether chlorambucil after treatment for H. pylori would help prevent recurrence. Patients were treated with antibiotics for H. pylori infection. Those with successful eradication of H. pylori and no evidence of progression of lymphoma were eligible for randomisation to chlorambucil or observation. Two hundred and thirty-one patients were registered. Ninety-seven percent patients had H. pylori eradicated after antibiotics and 59% achieved macroscopically normal gastric mucosa. One hundred and ten patients were randomised. With a median follow-up of 58 months, six patients were dead and 17 had recurrent/progressive disease. The recurrence/progression rates at 5 years were 11% for chlorambucil, and 21% for observation with a difference of 10%, 95% confidence interval (CI) = -9% to 29%, P = 0.15. No difference was detected in recurrence/progression-free survival [Hazard Ratio (HR) = 0.96, 95% CI = 0.41-2.2, P = 0.91] or overall survival (HR = 1.93, 95% CI = 0.39-9.58, P = 0.42). This is the first randomised trial to show there is no good evidence to support that additional single agent chemotherapy to anti-H. pylori treatment contributes to prevent recurrence in localised gastric MALT lymphomas.

Figures

Fig 1
Fig 1
Trial profile.
Fig 2
Fig 2
Cumulative incidence rate of recurrence/progression.
Fig 3
Fig 3
Recurrence/progression-free survival.
Fig 4
Fig 4
Overall survival.

References

    1. Bayerdorffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. Lancet. 1995;345:1591–1594.
    1. Bertoni F, Zucca E. State-of-the-art therapeutics:marginal-zone lymphoma. Journal of Clinical Oncology. 2005;23:6415–6420.
    1. Bertoni F, Conconi A, Capella C, Motta T, Giardini R, Ponzoni M, Pedrinis E, Novero D, Rinaldi P, Cazzaniga G, Biondi A, Wotherspoon A, Hancock B, Smith P, Souhami R, Cotter F, Cavalli F, Zucca E. International Extranodal Lymphoma Study Group and United Kingdom Lymphoma Group. Molecular follow-up in gastric mucosa-associated lymphoid tissue lymphomas: early analysis of the LY03 co-operative trial. Blood. 2002;99:2541–2544.
    1. Chini C, Pinotti G, Stathis A, Proserpio I, Bertoni F, Cavalli F, Zucca E. Long term outcome of gastric MALT lymphoma patients treated with anti-Helicobacter (antibiotic and proton-pump inhibitor) regimens. Blood. 2007;110:761a. Abs.# 2583. ASH Annual Meeting Abstracts.
    1. Copie-Bergman C, Wotherspoon A. MALT lymphoma pathology, initial diagnosis, and posttreatment evaluation. In: Cavalli F, Stein H, Zucca E, editors. Extranodal Lymphomas Pathology and Management. London: Informa Health Care; 2008. pp. 114–123.
    1. Ferrucci P, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years? British Journal of Haematology. 2007;136:521–538.
    1. Fischbach W, Goebeler ME, Ruskone-Fourmestraux A, Wundisch T, Neubauer A, Raderer M, Savio A. Most patients with minimal histological residuals of gastric MALT lymphoma after successful eradication of Helicobacter pylori can be managed safely by a watch and wait strategy: experience from a large international series. Gut. 2007;56:1685–1687.
    1. Hammel P, Haioun C, Chaumette MT, Gaulard P, Divine M, Reyes F, Delchier JC. Efficacy of single-agent chemotherapy in low-grade B-cell mucosa-associated lymphoid tissue lymphoma with prominent gastric expression. Journal of Clinical Oncology. 1995;13:2524–2529.
    1. Isaacson PG, Spencer J. Malignant lymphoma of mucosa-associated lymphoid tissue. Histopathology. 1987;11:445–462.
    1. Isaacson PG, Wright DH. Malignant lymphoma of mucosa associated lymphoid tissue: a distinctive type of B-cell lymphoma. Cancer. 1983;52:1410–1416.
    1. Koch P, Probst A, Berdel WE, Willich NA, Reinartz G, Brockmann J, Liersch R, del Valle F, Clasen H, Hirt C, Breitsprecher R, Schmits R, Freund M, Fietkau R, Ketterer P, Freitag EM, Hinkelbein M, Heinecke A, Parwaresch R, Tiemann M. Treatment results in localized primary gastric lymphoma: data of patients registered within the German multicenter study (GIT NHL 02/96) Journal Clinical Oncology. 2005;23:7050–7059.
    1. Levy M, Copie-Bergman C, Cameiro C, Chaumette M, Delfau-Larue M, Haioun C, Charachon A, Hemery F, Caulard P, Leroy K, Delchier JC. Prognostic value of translocation t(11;18) in tumour response of low-grade gastric lymphoma of mucosa-associated lymphoid tissue type to oral chemotherapy. Journal of Clinical Oncology. 2005;23:5061–5066.
    1. Liu H, Ye H, Ruskone-Fourmestraux A, De Jong D, Pileri S, Thiede C, Lavergne A, Boot H, Caletti G, Wundisch T. T(11;18) is a marker for all stage gastric MALT lymphomas that will not respond to H. pylori eradication. Gastroenterology. 2002;122:1286–1294.
    1. Martinelli G, Laszlo D, Ferreri AJ, Pruneri G, Ponzoni M, Conconi A, Crosta C, Pedrinis E, Bertoni F, Calabrese L, Zucca E. Clinical activity of rituximab in gastric marginal zone non-Hodgkin’s lymphoma resistant to or not eligible for anti-Helicobacter pylori therapy. Journal of Clinical Oncology. 2005;23:1979–1983.
    1. Pinotti G, Zucca E, Roggero E, Pascarella A, Bertoni F, Savio A, Savio E, Capella C, Pedrinis E, Saletti P, Morandi E, Santandrea G, Cavalli F. Clinical features, treatment and outcome in a series of 93 patients with low-grade gastric MALT lymphoma. Leukemia and Lymphoma. 1997;26:527–537.
    1. Roggero E, Zucca E, Pinotti G, Pascarella A, Capella C, Savio A, Pedrinis E, Paterlini A, Venco A, Cavalli F. Eradication of Helicobacter pylori infection in primary low- grade gastric lymphoma of mucosa-associated lymphoid tissue. Annals of Internal Medicine. 1995;122:767–769.
    1. Rohatiner A, d’Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, Lister TA, Norton A, Salem P, Shipp M. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Annals of Oncology. 1994;5:397–400.
    1. Ruskone-Fourmestraux A, Lavergne A, Aegerter PH, Megraud F, Palazzo L, de Mascrarel A, Molina T, Rambaud JL. Predictive factors for regression of gastric MALT lymphoma after anti-Helicobacter pylori treatment. Gut. 2001;48:297–303.
    1. Stolte M, Bayerdorffer E, Morgner A, Alpen B, Wundish T, Thiede C, Neubauer A. Helicobacter and gastric MALT lymphoma. Gut. 2002;50:19–24.
    1. Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet. 1991;338:1175–1176.
    1. Wotherspoon AC, Doglioni C, Diss TC, Pan L, Moschini A, De Boni M, Issacson PG. Regression of primary low grade B-cell gastric lymphoma of mucosa associated lymphoid tissue (MALT) type following eradication of Helicobacter pylori. Lancet. 1993;342:575–577.
    1. Wundisch T, Thiede C, Morgner A, Dempfle A, Gunther A, Liu H, Ye H, Du MQ, Kim TD, Bayerdorffer E, Stolte M, Neubauer A. Long-term follow-up of gastric MALT after Helicobacter pylori eradication. Journal of Clinical Oncology. 2005;23:8018–8024.
    1. Yoon SS, Coit DG, Portlock CS, Karpeh MS. The diminishing role of surgery in the treatment of gastric lymphoma. Annals of Surgery. 2004;240:28–37.

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