Final Results of European Trial in Mucosa-Associated Lymphoid Tissue Lymphoma
The final results of the European phase III International Extranodal Lymphoma Study Group (IELSG)-19 trial, reported in the Journal of Clinical Oncology by Zucca et al, showed that event-free and progression-free survival were better with rituximab (Rituxan) plus chlorambucil vs either agent alone in patients with mucosa-associated lymphoid tissue (MALT) lymphoma; however, no differences in overall survival were observed. The IELSG-19 trial was the first randomized study to examine systemic therapy for MALT lymphoma.
Study Details
The trial, conducted in 78 centers in 6 countries, initially randomized patients to first-line treatment with chlorambucil alone (6 mg/m2/d on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or the combination of chlorambucil (same schedule) plus rituximab (375 mg/m2 on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21. After planned enrollment of 252 patients, the protocol was amended to continue with a 3-arm design (1:1:6 ratio), incorporating a new arm of rituximab alone (same schedule). In total, 454 patients were randomized to receive chlorambucil alone (n = 151), chlorambucil plus rituximab (n = 152), or rituximab alone (n = 151. A 5-year analysis reported in 2013 showed superior event-free survival, the primary study endpoint, with rituximab plus chlorambucil vs chlorambucil.
Outcomes
Median follow-up was 7.4 years. Median event-free survival was not reached in the combination group (hazard ratio [HR] = 0.54, 95% confidence interval [CI]= 0.38–0.77, vs chlorambucil; overall P = .0009), 5.1 years in the chlorambucil group, and 5.6 years with rituximab alone (HR = 0.97, 95% CI = 0.69–1.35, vs chlorambucil). Five-year event-free survival was 68%, 51%, and 50%. Median progression-free survival was not reached for the combination (HR = 0.62, 95% CI = 0.42–0.93; overall P = .0119), 8.3 years for chlorambucil, and 6.9 years for rituximab (HR = 1.10, 95% CI = 0.76–1.59). Five-year progression-free survival was 72%, 59%, and 57%.
Median overall survival was not reached in any group, and there were no significant differences between the groups (overall P = .464). Compared with the chlorambucil group, hazard ratios were 1.24 (95% CI = 0.69–2.23) for the combination group and 0.91 (95% CI = 0.44–1.86) for the rituximab group. Five-year overall survival rates were 90% in the combination group, 89% in the chlorambucil group, and 92% in the rituximab group.
All treatments were well tolerated, with no unexpected toxicities being observed.
The investigators concluded: “Rituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in [event-free survival] and progression-free survival did not translate into longer overall survival.”
The study was supported by grants from Oncosuisse and Roche.
Emanuele Zucca, MD, of the IELSG Operation Office, Oncology Institute of Southern Switzerland, is the corresponding author of the Journal of Clinical Oncology article.
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