A pilot phase II study of ofatumumab monotherapy for extranodal marginal zone B‐cell lymphoma of the mucosa‐associated lymphoid tissue (MALT) lymphoma

Abstract

These are the final results of the Ofatumumab in MALT lymphoma study (O‐MA 1), a pilot phase II trial evaluating the capacity and safety of ofatumumab to induce objective responses in patients with Helicobacter pylori eradication refractory or extragastric MALT lymphoma. Ofatumumab was given at 4 weekly doses (1000 mg) followed by 4 doses at 2‐month intervals starting at week 8. According to protocol, a total of 16 patients were recruited (median age 69 years; range 38‐85). Thirty one percent (5/16) of patients had primary gastric MALT lymphoma while the remaining 69% (11/16) presented with extragastric manifestations. Seventy‐five percent (12/16) had localized lymphoma and 4 patients disseminated disease. The overall response rate to treatment with ofatumumab was 81% (13/16), with the median time to best response being 5.5 months. In detail, 50% (8/16) achieved complete remission; 31% (5/16), partial remission; and 19% (3/16), disease stabilization as best response. However, 1 patient with gastric lymphoma and complete remission at second restaging had a relapse at final assessment but ongoing complete remission during further follow‐up. Tolerability was excellent accept low‐grade infusion reactions occurring in 86% (14/16). At a median follow‐up time of 25 months only 1 patient has relapsed suggesting durable responses in the majority of patients. This pilot trial shows clearly that ofatumumab is active and safe for the treatment of MALT lymphoma.

Immunomodulatory treatment for mucosa‐associated lymphoid tissue lymphoma (MALT lymphoma)

“…The presence of plasmacytic differentiation might be of interest in this context, as plasma‐cells are CD20‐negative; an increase of plasmacytic differentiation following application of R has been reported in patients with MALT lymphoma 54 . Furthermore, the second generation compound ofatumumab, and also the CD20‐based radio‐immunotherapy with 90Y‐ibritumomab‐tiuxetan have been tested and found active in this context 47,49 . Ofatumumab was evaluated in a pilot trial of 16 patients (31% gastric patients, 69% extragastric patients) resulting in an ORR of 81% and 50% CRs, and while larger series and long‐term data are missing, this appears to be at least as effective as R‐monotherapy based on these pivotal data 47 .…”

“…Furthermore, the second generation compound ofatumumab, and also the CD20‐based radio‐immunotherapy with 90Y‐ibritumomab‐tiuxetan have been tested and found active in this context 47,49 . Ofatumumab was evaluated in a pilot trial of 16 patients (31% gastric patients, 69% extragastric patients) resulting in an ORR of 81% and 50% CRs, and while larger series and long‐term data are missing, this appears to be at least as effective as R‐monotherapy based on these pivotal data 47 . Radio‐immunotherapy with 90Y‐ibritumomab‐tiuxetan, was in addition to preliminary retrospective data, investigated in a phase II study including a total of 30 patients (43% gastric, 57% extragastric) 49 .…”

How I treat MALT lymphoma: ‘a subjective interpretation of the gospel according to Isaacson….’

“… 10 In the O-MA1 trial, ofatumumab showed an ORR of 81% with a CR rate of 50% in 16 patients with MALT lymphoma. 11 Those next generation compounds might be of interest for further studies to potentially overcome resistance to R-monotherapy and also for combination regimens.…”

Incidentally Discovered Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue in the Colon

“…Hence, the decision of radiation versus chemotherapy can be made based on individual patient's profile and the center's experience [ 19 ]. In advanced stage disease when systemic treatment is needed, chemotherapy and/or immunotherapy with anti-CD20 monoclonal antibodies can be considered [ 19 , 20 ]. Surgical resection is recommended when a colorectal MALT lymphoma does not respond to eradication therapy or chemotherapy, provided it is localized without dissemination [ 21 ].…”