Emanuele Zucca, MD
The final results of the European phase III International Extranodal Lymphoma Study Group (IELSG)-19 trial, reported in the Journal of Clinical Oncology by Emanuele Zucca, MD, of the IELSG Operation Office, Oncology Institute of Southern Switzerland, and colleagues 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.
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.
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. ■
Zucca E, et al: J Clin Oncol 35:1905-1912, 2017.