Patients who have mucosa-associated lymphoid tissue lymphoma and are treated with chlorambucil plus rituximab have better event-free survival and progression-free survival than do comparable patients treated with either drug alone, according to findings from a randomized phase III study.
In the International Extranodal Lymphoma Study Group study (IELSG-19), 5-year event-free survival was 70% in 131 patients treated with the combination therapy, 52% in 130 patients treated with chlorambucil alone, and 51% in 132 patients treated with rituximab alone. Progression-free survival also was significantly improved in the combination therapy arm compared with the two single-agent arms, Dr. Emanuele Zucca reported at the annual International Conference on Malignant Lymphoma in Lugano, Switzerland.
Overall survival at 5 years, however, was similar at about 90% for all three treatment arms, according to Dr. Zucca of the Oncology Institute of Southern Switzerland, Ospedale San Giovanni, Bellinzona.
Hematologic toxicity was more pronounced in the combination therapy arm than in the single-agent arms, but there were no unexpected severe side effects, Dr. Zucca reported.
IELSG-19 is the largest randomized study to date in MALT lymphoma, and is the first to compare combination chlorambucil and rituximab with both agents alone, he said.
The primary lymphoma site was the stomach in 43% of the393 study participants, and 34% had lymph node involvement. The international prognostic index score was low or low-intermediate in 81%. Just 8% of the patients had prior local therapy, Dr. Zucca said.
Study participants were adults with disseminated extranodal marginal zone B-cell lymphoma or localized disease not amenable to local therapy. Those randomized to the chlorambucil therapy arm received 6 mg/m2 of oral chlorambucil daily for 6 weeks, and those who responded or who had stable disease received the same dose daily for 14 consecutive days every 28 days for four cycles. Those in the combination therapy arm received the chlorambucil dosing, plus 375 mg/m2 of rituximab intravenously on days 1, 8, 15, 22, 56, 84, 112, and 140. Those in the rituximab-only group received the same rituximab dosing without chlorambucil.
In a published report of the outcomes in patients enrolled in the first two protocol arms (combination therapy and chlorambucil-only therapy), Dr. Zucca and his colleagues noted that survival rates in patients with MALT lymphoma are typically high. The significant differences in event-free survival have not yet translated into improved overall survival (J. Clin. Oncol 2013 Jan. 7 [doi:10.1200/JCO.2011.40.6272]).
Nonetheless, the findings – among the first to demonstrate the activity of chlorambucil with and without rituximab in MALT lymphoma – suggest the combination is a safe and effective approach that could improve outcomes, Dr. Zucca said.
The findings he presented expand upon the initial published analysis by including data from the rituximab-only arm, which was added following a more-rapid-than-expected initial recruitment into the combination and chlorambucil-only arms.
These findings are of note, because aside from H. pylori eradication for localized gastric disease, no consensus exists on the standard therapy for MALT lymphoma, he said.
Several study authors reported serving as consultants for or receiving honoraria from Roche International, which sponsored the IELSG-19 study.