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

A phase 3 trial in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. Patients were initially randomised 1 to 1 between chlorambucil 6 mg per square metre daily on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18 and 21 to 22, and the same chlorambucil with rituximab 375 mg per square metre on day 1 of weeks 1, 2, 3, 4, 9, 13, 17 and 21. After the planned enrolment of 252 patients the protocol was amended to a three-arm design in a 1 to 1 to 6 ratio, adding a rituximab monotherapy arm, for a final sample of 454.

At a median follow-up of 7.4 years, five-year event-free survival was 51 per cent (95 per cent confidence interval 42 to 60) with chlorambucil alone, 50 per cent (42 to 59) with rituximab alone and 68 per cent (60 to 76) with the combination (p = 0.0009); the hazard ratio for the combination against chlorambucil was 0.54 (0.38 to 0.77). Progression-free survival was also significantly better with the combination (p = 0.0119). Five-year overall survival was approximately 90 per cent in each arm. No unexpected toxicities were recorded.