Final results of the phase II O-MA 1 trial – ofatumumab demonstrates efficacy and a favorable toxicity profile in MALT Lymphoma

On 10^th July 2017, in Hematological Oncology, Barbara Kiesewetter, MD, from the Medical University of Vienna, Austria, et al. published final results of the pilot, single-center, one-arm, phase II Ofatumumab in Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma study (O-MA 1; EudraCT Number 2012-005223-32).

The trial aimed to assess the ability and safety of ofatumumab in inducing objective responses in patients with Helicobacter pylori eradication refractory or extra-gastric MALT Lymphoma. Patients received ofatumumab at 4 weekly doses of 1,000 mg IV (induction phase) then 4 doses at 1,000mg every 2 months starting at week 8 (consolidation phase) with the last dose being administered at week 32.

Key Highlights:

Treatment and response:

• Sixteen pts recruited (median age, 69 years; range, 38–85); most (13/16, 81%) were >60 years
• Median time from last treatment = 12.9 months (range, 4.0–51.0)
• Median time from diagnosis to ofatumumab = 12.3 months (range, 2.0–166.0)
• Median follow-up = 25.1 months (range, 13.0–37.0)
• ORR = 81%; CR = 50%; PR = 31%; SD = 19%
• Median time to best response = 5.5 months (range, 2.5–9.9)
• Number of applied ofatumumab doses = 124; 15/16 pts completed the study per protocol
• Response Rate (RR) at first restaging in week 12 (+/- 2 weeks) = 62%; RR at second restaging in week 24 (+/- 2 weeks) = 75%; at final response evaluation = 81%
• Three patients improved to better response between restaging at weeks 12 and 24 (SD to PR = 1; SD to CR = 1; PR to CR = 1) and 2 more pts improved between week 24 and end of treatment (SD to PR = 1; PR to CR = 1)
• RR for gastric versus extra-gastric pts (100% vs 73%; P = 0.59) and for localized versus disseminated disease (83% vs 75%; P = 1.000) was not significantly different
• Of rituximab pretreated pts, 75% (3/4) responded to ofatumumab therapy (CR = 1; PR = 2)
• One patient has relapsed at 21-month follow-up after initial CR at end of treatment, the patient died due to Lymphoma progression
• Seven pts (44%) are in ongoing CR and without Lymphoma

Toxicity:

• Of the 16 pts, one stopped study therapy due to prolonged hospitalization for erysipelas unrelated to study medication
• Infusion Related Reactions (IRRs): grade I = 3 pts (19%); grade II = 11 pts (69%)
• Grade II respiratory infection reported in 1 patient
• Lymphopenia: grade II = 3 pts (19%); grade III = 1 patient (6%)
• No dose reductions due to toxicity were performed

The authors concluded that, based on the results of this pilot study, ofatumumab demonstrated efficacy and was well tolerated in patients with extranodal MALT Lymphoma. Indeed, it’s toxicity profile appears so favorable that it presents as an attractive option as salvage treatment of elderly or frail patients. Moreover, the anti-CD20 antibody demonstrated efficacy in patients with the relapsed form of disease who had previously received rituximab. The authors did acknowledge that the number of patients in the trial was small but the RRs seemed to be just as good, if not better, than rituximab monotherapy. The group emphasized that larger trials should be conducted to assess ofatumumab in a larger patient cohort and also to investigate it as part of combination chemoimmunotherapeutic strategies.

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.