Ofatumumab Shows Limited Activity in Previously Untreated Follicular Lymphoma

February 20, 2019
Leah Lawrence
Leah Lawrence

In this study, single-agent ofatumumab did not show superiority to rituximab or obinutuzumab, raising the question of whether ofatumumab should have a role in the treatment of follicular lymphoma.

Single-agent ofatumumab administered by extended induction resulted in a high response rate and was well tolerated among patients with treatment-naive advanced-stage follicular lymphoma (FL) with a low/intermediate-risk FLIPI score. However, researchers led by Cara A. Rosenbaum, MD, of Meyer Cancer Center at Weill Medical College of Cornell University, and colleagues, noted that “this antibody does not appear superior to either rituximab or obinutuzumab at the doses and extended-dosing schedule used in this study and, therefore, its future in FL remains questionable.”

Obinutuzumab in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and bendamustine has been shown to be highly active in patients with untreated FL, with efficacy similar to rituximab-based immunochemotherapy. However, results of a trial comparing ofatumumab and rituximab in the relapsed/refractory setting failed to show superiority of ofatumumab.

“Whether there is clinical benefit of single-agent ofatumumab or obinutuzumab over rituximab in treatment-naive patients with lower tumor burden remains unanswered,” the researchers wrote. “Partial supporting evidence for this hypothesis is provided by the GALLIUM study, in which previously untreated, symptomatic, advanced-stage FL patients were randomized to obinutuzumab 1,000 mg vs standard rituximab-based immunochemotherapy and maintenance. Despite a similar overall response rate and lower complete response rate, a prolonged 3-year progression-free survival (PFS) was observed with obinutuzumab vs rituximab maintenance therapy following immunochemotherapy induction.”

However, obinutuzumab has not been studied as a single agent in advanced FL patients with low tumor burden.

In this phase II study published in the British Journal of Haematology, the researchers hypothesized that ofatumumab may have significant efficacy in patients with low-tumor-burden advanced FL who were naive to rituximab. The study was originally designed to evaluate two doses of ofatumumab-500 mg and 1,000 mg-but the 500-mg arm was discontinued due to slow accrual.

Fifty-one patients were enrolled; 15 were randomly assigned to the 500-mg arm and 36 to the 1,000-mg arm. Patients received 4 weekly 1,000-mg doses followed by 4 extended-induction doses once every 8 weeks.

Among patients assigned to the 1,000-mg dose, the overall response rate was 84%, with a median duration of response of almost 2 years (23.7 months). By 12 months, 9% of patients achieved complete response, 75% achieved partial response, and 9% had stable disease. Of patients who achieved a complete or partial response as best response, the majority (66%) had responded to therapy by month 3. The median PFS was 1.9 years. All patients remain alive.

Patients experienced no grade 4 infusion reactions and no grade 3/4 infections. Grade 3 infusion reactions occurred in one-quarter of patients in the 1,000-mg arm.

“Durability of response to extended-induction ofatumumab in this study appears inferior to that reported for similar extended-dosing regimens of rituximab monotherapy in chemotherapy-naive, low-tumor-burden FL,” the researchers wrote. “At median follow-up of 30.7 months in the 1,000-mg arm, 31% of patients remain in remission, yielding a 1-year PFS of 90% and median PFS of 22.8 months. Prolonged median event-free/PFS durations of 34–42 months were comparatively observed in studies of rituximab extended-induction dosing.”