title: First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial.
abstract: BACKGROUND
  No standard first-line systemic treatment for mucosa-associated lymphoid tissue (MALT) lymphoma is available. In a phase 2 study we aimed to assess the safety and activity of a response-adapted combination of bendamustine plus rituximab as upfront treatment for this type of lymphoma.
  
  
  METHODS
  In a multicentre, single-arm, non-randomised, phase 2 trial, we enrolled patients with MALT lymphoma at any site and stage and treated them with bendamustine (90 mg/m(2) on days 1 and 2) plus rituximab (375 mg/m(2) on day 1), every 4 weeks. Inclusion criteria were measurable or evaluable disease, age 18-85 years, and unequivocal active lymphoma; we also enrolled patients with MALT lymphoma arising in the stomach after failure of Helicobacter pylori eradication and primary cutaneous cases after failure of local therapies. Exclusion criteria included evidence of histological transformation, CNS involvement, and active hepatitis B or C virus or HIV infection. After three cycles, patients achieving complete response received one additional cycle (total four cycles) and those achieving partial response received three additional cycles (total six cycles). The primary endpoint was 2-year event-free survival. Analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01015248.
  
  
  RESULTS
  60 patients from 19 centres in Spain were enrolled between May 27, 2009, and May 23, 2011, and received treatment; 57 patients were evaluable for the primary endpoint. Only 14 (25%) patients needed more than four cycles of treatment. After a median follow-up of 43 months (IQR 37-51), median event-free survival was not reached. Event-free survival at 2 years was 93% (95% CI 84-97) and at 4 years was 88% (95% CI 74-95). The most frequently observed grade 3-4 adverse events were haematological: lymphopenia in 20 (33%) patients, neutropenia in 12 (20%) patients, and leucopenia in three (5%) patients. Grade 3-4 febrile neutropenia or infections were reported in three (5%) and four (7%) patients, respectively.
  
  
  CONCLUSIONS
  This response-adapted schedule of bendamustine plus rituximab appears to be an active and well tolerated first-line treatment for patients with MALT lymphoma.
  
  
  BACKGROUND
  Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO), Mundipharma Spain, and Roche Pharma Spain.
authors.affiliation: Department of Hematology, Hospital del Mar, Barcelona, Spain. Electronic address: 94131@parcdesalutmar.cat.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salar
authors.affiliation: Department of Hematology, Hospital Durans i Reynals, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Domingo-Domenech
authors.affiliation: Department of Hematology, Clínica Universitaria de Navarra, Pamplona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Panizo
authors.affiliation: Department of Hematology, Hospital Central de Asturias, Asturias, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Nicolás
authors.affiliation: Department of Hematology, Hospital Son Llatzer, Mallorca, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Bargay
authors.affiliation: Department of Hematology, Hospital Universitario Mutua de Terrassa, Terrassa, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Muntañola
authors.affiliation: Department of Hematology, Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Canales
authors.affiliation: Department of Hematology, Complejo Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Bello
authors.affiliation: Department of Hematology, Hospital Germans Trias i Pujol, Badalona, Spain.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Sancho
authors.affiliation: Department of Hematology, MD Anderson Cancer Center, Madrid, Spain.
authors.forename: José Francisco
authors.initials: JF
authors.lastname: Tomás
authors.affiliation: Department of Hematology, Hospital Universitario de Canarias, Tenerife, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Rodríguez
authors.affiliation: Department of Hematology, Hospital Fundación Alcorcón, Alcorcón, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Peñalver
authors.affiliation: Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Grande
authors.affiliation: Department of Hematology, Hospital Morales Meseguer, Murcia, Spain.
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Sánchez-Blanco
authors.affiliation: Department of Hematology, Hospital Clínico Lozano Blesa, Zaragoza, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Palomera
authors.affiliation: Department of Hematology, Hospital Universitario La Princesa, Madrid, Spain.
authors.forename: Reyes
authors.initials: R
authors.lastname: Arranz
authors.affiliation: Department of Hematology, Hospital Marqués de Valdecilla, Santander, Spain.
authors.forename: Eulogio
authors.initials: E
authors.lastname: Conde
authors.affiliation: Department of Anatomic Pathology, Hospital del Mar, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: García
authors.affiliation: Department of Anatomic Pathology, MD Anderson Cancer Center, Madrid, Spain.
authors.forename: Juan Fernando
authors.initials: JF
authors.lastname: García
authors.affiliation: Department of Hematology, Hospital Clínico de Salamanca, Salamanca, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.affiliation: Department of Hematology, MD Anderson Cancer Center, Madrid, Spain; Department of Internal Medicine, Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Montalbán