Patients with advanced mucosa-associated lymphoid tissue (MALT) lymphoma are often treated with chemotherapy-based regimens; however, because of the indolent course of the disease, researchers are investigating immunomodulatory, chemotherapy-free strategies, including the combination of lenalidomide and rituximab. In a Letter to the Editor published in Blood, Barbara Kiesewetter, MD, of the Division of Oncology at the Medical University of Vienna in Austria, and authors reported interim results of the phase II AGMT MALT-2 trial, which was designed to assess the feasibility of this treatment combination in patients with MALT lymphoma.
The study enrolled patients with gastric and extragastric MALT lymphoma (if they were Helicobacter pylori [HP]-negative or had successful elimination of HP) who had adequate blood counts (defined as an absolute neutrophil count of ≥1,000/μL and a platelet count of ≥60×109/L).
Of 46 evaluable patients (median age = 64 years; range = 32-84 years), most (n=28; 61%) were female and had received the following prior treatments:
- systemic (immunotherapy/chemotherapy; n=11; 24%)
- rituximab-containing regimens (n=9; 20%)
- prior lenalidomide (n=1; 2%)
- >2 prior lines of therapy (n=9; 20%)
Patients received lenalidomide 20 mg administered orally on days one through 21, followed by seven days of no treatment, and rituximab 375 mg/m2 administered intravenously on day one of each 28-day cycle.
After three treatment courses, patients were assessed and were treated according to response:
- Patients who achieved stable disease (SD) or better received another 3 treatment cycles.
- Patients who achieved complete response (CR) after 6 cycles stopped treatment, whereas those who achieved partial response (PR) or SD received another 2 cycles for a maximum of 8 cycles.
Patients received an average of six treatment cycles (range = 5 to 8 cycles), with 54 percent (n=25) receiving six, 28 percent (n=13) receiving eight, and 17 percent (n=8) receiving five or fewer cycles.
After a median follow-up of 27 months (range = 13.2-36.3 months), the overall response rate was 80 percent (n=37; 95% CI 69-92), with a median time to best response of 3.6 months (range = 2.8-5.8 months).
Twenty-five patients (54%; 95% CI 40-69) achieved CR, 12 (26%; 95% CI 13-39) achieved PR, and eight (17%; 95% CI 6-28) had SD. One patient with gastric MALT lymphoma demonstrated progressive disease (PD) at first restaging but “was successfully salvaged with rituximab plus bendamustine and is an ongoing remission for >18 months,” the authors reported. “Remarkably, two patients given only one cycle due to adverse events (AEs) showed durable PR, now ongoing for longer than 15 and 20 months.”
Eleven patients (24%) converted to a better response between the first and second restaging, and an additional three patients (7%) improved from cycle six to eight. Two patients whose initial best response was SD and PR had PD at final restaging after cycle eight.
Though there was a trend toward worse response in patients with elevated lactate dehydrogenase at baseline (p=0.079) compared to those without, univariate analysis revealed no significant differences in response related to patient demographics (including gender, localization, dissemination status, and prior treatment).
Three patients relapsed during study follow-up (occurring 5-8.8 months after response), for a 91 percent progression-free survival rate. These data “suggest durable responses in the majority of cases,” Dr. Kiesewetter and authors wrote.
In the safety analysis, which included data from 48 patients who received at least one dose of rituximab plus lenalidomide, 18 patients (38%) experienced mild infusion reactions related to rituximab administration. AEs associated with lenalidomide included mild musculoskeletal pain (42%), mild fatigue (33%), cough/respiratory infections (33%), diarrhea (23%), and mild vertigo (23%). Exanthema occurred in 46 percent of patients but was typically mild. Grade ≥3 hematologic AEs included neutropenia (n=9), leukopenia (n=2), and anemia (n=1).
“Late remissions appear to be a common phenomenon in patients treated with immunomodulators [like lenalidomide] for MALT lymphoma, and long-term effects of rituximab [plus] lenalidomide might still be underestimated in [our] analysis,” the authors concluded. Rituximab plus lenalidomide was “equally effective” for pretreated and non-treated patients, demonstrating that this combination appears to be “feasible, safe, and active for treating patients with MALT lymphoma, irrespective of primary localization and pretreatment.”
The study is limited by its heterogeneous patient population and its short follow-up, along with the lack of a comparator group.
Kiesewetter B, Willenbacher E, Willenbacher W, et al. A phase 2 study of rituximab plus lenalidomide for mucosa-associated lymphoid tissue lymphoma. Blood. 2017;129:383-5.