This phase II study aimed to evaluate the tolerability and activity of the monoclonal anti-CD20 antibody rituximab (Rituxan) in patients with either untreated or relapsed biopsy-proven extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type, with measurable or evaluable disease. Treatment consisted of rituximab at 375 mg/m² IV weekly for 4 weeks. Response assessments were planned at 2, 6, and 12 months after the start of treatment.
Between January 2000 and May 2001, when enrollment was closed, 35 patients (24 females, 11 males) were registered; four patients had been previously treated with anthracycline-containing chemotherapy and seven with alkylating agents. Median age was 57 years (range: 27-85 years). Fifteen patients had a primary gastric marginal zone lymphoma, two of which had no evidence of prior Helicobacter pylori (HP) infection, and the remaining had previously received anti-HP therapy and were HP negative with evidence of lymphoma progression at study entry, after a median time of 25 months (range: 5-89 months) from eradication. Twenty patients had a primary nongastric localization (7 skin/subcutaneous, 4 lung, 4 salivary gland, 3 orbit, 1 breast, and 1 liver); in seven of these cases multiple mucosal sites were involved.
At study entry, 12 patients had Ann Arbor stage I disease, 3 stage II, and 20 stage IV; bone marrow involvement was documented in 9 patients; 2 patients had B symptoms; and lactate dehydrogenase was elevated in three cases. All patients had Eastern Cooperative Oncology Group performance status £ 1. A total of 34 patients completed the treatment program; one patient refused to receive the third and fourth planned doses and was lost to follow-up.
At a median follow-up of 12 months, 34 patients had at least one response assessment, and 26 patients were assessed for response 6 months after treatment. By standard criteria, the overall response rate among the 34 fully evaluated patients was 73% (95% confidence interval: 56%-87%), with 15 complete responses and 10 partial responses. The median time to best response was 2.2 months (range: 1-5.6 months) from the beginning of treatment. Three patients had disease progression immediately after treatment, and three patients relapsed after complete response at 6.6, 9.7, and 10.1 months.
Toxicity was mild, with only two cases of rapidly regressing grade 3 toxicity (bronchospasm and glottis edema) during the first infusion and one case of grade 3 infection (pneumonia). Grade 1/2 allergic skin rashes were reported in three patients. Grade 2 gastric bleeding was reported in one patient; grade 1 asthenia and myalgias in two cases. Two cases of infusion-related grade 1/2 hypotension and two cases of grade 2 fever were documented.
CONCLUSION: These results show promising efficacy of rituximab as a single agent in patients with extranodal marginal zone lymphoma.