Final Results of the IELSG-19 Randomized Trial of Mucosa-Associated Lymphoid Tissue Lymphoma: Improved Event-Free and Progression-Free Survival With Rituximab Plus Chlorambucil Versus Either Chlorambucil or Rituximab Monotherapy

Emanuele Zucca, Annarita Conconi, Giovanni Martinelli, Reda Bouabdallah, Alessandra Tucci, Umberto Vitolo, Maurizio Martelli, Ruth Pettengell, Gilles Salles, Catherine Sebban, Armando Lopez Guillermo, Graziella Pinotti, Liliana Devizzi, Franck Morschhauser, Hervé Tilly, Valter Torri, Stefan Hohaus, Andrés J M Ferreri, Pierre Zachée, André BoslyCorinne Haioun, Caterina Stelitano, Monica Bellei, Maurilio Ponzoni, Anne Moreau, Andrew Jack, Elias Campo, Luca Mazzucchelli, Franco Cavalli, Peter Johnson, Catherine Thieblemont

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and Methods Eligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m2/d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. Results At a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination ( P = .0009). Progression-free survival was also significantly better with the combination ( P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. Conclusion Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.

Original languageEnglish
Pages (from-to)1905-1912
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number17
DOIs
Publication statusPublished - Jun 10 2017

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols
  • Chlorambucil
  • Disease-Free Survival
  • Endpoint Determination
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lymphoma, B-Cell, Marginal Zone
  • Male
  • Middle Aged
  • Rituximab
  • Treatment Outcome
  • Clinical Trial, Phase III
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

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