First Line Systemic Treatment for MALT Lymphoma—Do We Still Need Chemotherapy? Real World Data from the Medical University Vienna

SIMPLE SUMMARY: The Division of Oncology at the Medical University Vienna is a tertiary referral center for extranodal lymphoma of mucosa-associated lymphoid tissue (MALT)-type and currently oversees more than 400 patients with this diagnosis, including a relevant percentage of patients being treated with systemic therapies. In the current analysis, we present response and long-term data of 159 patients (not eligible for Helicobacter pylori eradication) treated upfront with systemic treatment focusing on chemotherapy- versus immunotherapy-based strategies. We show that despite higher response and complete remission rates for chemo- versus immunotherapy, there appears to be no difference in progression-free survival, thus suggesting comparable long-term results. Considering the biological background of MALT lymphoma—and particularly its high dependence on the tumor microenvironment—but also the favorable toxicity profile of assessed immunomodulatory agents such as IMiD lenalidomide or macrolide clarithromycin, we suggest that these data support further investigation of chemotherapy-free treatment concepts for MALT lymphoma. ABSTRACT: There is no clear therapeutic algorithm for mucosa-associated lymphoid tissue (MALT) lymphoma beyond Helicobacter pylori eradication and while chemotherapy-based regimens are standard for MALT lymphoma patients in need of systemic treatment, it appears of interest to also investigate chemotherapy-free strategies. We have retrospectively assessed MALT lymphoma patients undergoing upfront systemic treatment, classified either as chemotherapy (=classical cytostatic agents +/− rituximab) or immunotherapy (=immunomodulatory agents or single anti-CD20 antibodies) at the Medical University Vienna 1999–2019. The primary endpoint was progression-free survival (PFS). In total, 159 patients were identified with a median follow-up of 67 months. The majority of patients had extragastric disease (80%), but we also identified 32 patients (20%) with Helicobacter pylori negative or disseminated gastric lymphoma. Regarding the type of first line treatment and outcome, 46% (74/159) received a chemotherapy-based regimen and 54% (85/159) immunotherapy including IMiDs lenalidomide/thalidomide (37%), anti-CD20-anitbodies rituximab/ofatumumab (27%), macrolides clarithromycin/azithromycin (27%) and proteasome inhibitor bortezomib (9%). Median PFS was 76 months (95%CI 50–102), and while the overall response (90% vs. 68%, p < 0.01) and the complete remission rate (75% vs. 43%, p < 0.01) was significantly higher for chemotherapy, there was no difference in PFS between chemotherapy (median 81 months, 95%CI 47–116) and immunotherapy (76 months, 95%CI 50–103, p = 0.57), suggesting comparable long-term outcomes. To conclude, our data show higher response rates with chemo- compared to immunotherapy, but this did not translate into a superior PFS. Given the biological background of MALT lymphoma, and the favorable toxicity profile of novel immunomodulatory treatments, this should be further investigated.