Antonio Salar1, Eva Domingo-Domenech2, Carlos Panizo3, Concepción Nicolás4, Joan Bargay5, Ana Muntañola6, Miguel Canales7, José Luis Bello8, Juan Manuel Sancho9, José Francisco Tomás10, María José Rodríguez11, Francisco Javier Peñalver12, Carlos Grande13, José Javier Sánchez-Blanco14, Luis Palomera15, Reyes Arranz16, Eulogio Conde17, Mar García18, Juan Fernando García19, Dolores Caballero20, Carlos Montalbán21. 1. Department of Hematology, Hospital del Mar, Barcelona, Spain. Electronic address: 94131@parcdesalutmar.cat. 2. Department of Hematology, Hospital Durans i Reynals, Barcelona, Spain. 3. Department of Hematology, Clínica Universitaria de Navarra, Pamplona, Spain. 4. Department of Hematology, Hospital Central de Asturias, Asturias, Spain. 5. Department of Hematology, Hospital Son Llatzer, Mallorca, Spain. 6. Department of Hematology, Hospital Universitario Mutua de Terrassa, Terrassa, Spain. 7. Department of Hematology, Hospital Universitario La Paz, Madrid, Spain. 8. Department of Hematology, Complejo Universitario de Santiago, Santiago de Compostela, Spain. 9. Department of Hematology, Hospital Germans Trias i Pujol, Badalona, Spain. 10. Department of Hematology, MD Anderson Cancer Center, Madrid, Spain. 11. Department of Hematology, Hospital Universitario de Canarias, Tenerife, Spain. 12. Department of Hematology, Hospital Fundación Alcorcón, Alcorcón, Spain. 13. Department of Hematology, Hospital Universitario 12 de Octubre, Madrid, Spain. 14. Department of Hematology, Hospital Morales Meseguer, Murcia, Spain. 15. Department of Hematology, Hospital Clínico Lozano Blesa, Zaragoza, Spain. 16. Department of Hematology, Hospital Universitario La Princesa, Madrid, Spain. 17. Department of Hematology, Hospital Marqués de Valdecilla, Santander, Spain. 18. Department of Anatomic Pathology, Hospital del Mar, Barcelona, Spain. 19. Department of Anatomic Pathology, MD Anderson Cancer Center, Madrid, Spain. 20. Department of Hematology, Hospital Clínico de Salamanca, Salamanca, Spain. 21. Department of Hematology, MD Anderson Cancer Center, Madrid, Spain; Department of Internal Medicine, Hospital Universitario Ramón y Cajal, Madrid, Spain.
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. FINDINGS: 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. INTERPRETATION: This response-adapted schedule of bendamustine plus rituximab appears to be an active and well tolerated first-line treatment for patients with MALT lymphoma. FUNDING: Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO), Mundipharma Spain, and Roche Pharma Spain.
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. FINDINGS: 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. INTERPRETATION: This response-adapted schedule of bendamustine plus rituximab appears to be an active and well tolerated first-line treatment for patients with MALT lymphoma. FUNDING: Grupo Español de Linfomas/Trasplante de Médula Ósea (GELTAMO), Mundipharma Spain, and Roche Pharma Spain.
Authors: Andreas Engert; Carlo Balduini; Anneke Brand; Bertrand Coiffier; Catherine Cordonnier; Hartmut Döhner; Thom Duyvené de Wit; Sabine Eichinger; Willem Fibbe; Tony Green; Fleur de Haas; Achille Iolascon; Thierry Jaffredo; Francesco Rodeghiero; Gilles Salles; Jan Jacob Schuringa Journal: Haematologica Date: 2016-01-27 Impact factor: 9.941