Phase 2 Trial of Obinutuzumab for Advanced DLBCL

New Orleans—Patients newly diagnosed with diffuse large B-cell lymphoma (DLBCL) tolerated a regimen of obinutuzumab and chemotherapy, according to a phase 2, open label, multicenter, single arm trial. The authors mentioned preliminary results indicated the combination treatment was effective and provided further rationale for an ongoing phase 3 trial comparing obinutuzumab and rituximab.

Results were presented during a poster presentation at the ASH meeting. The poster was titled Safety and Efficacy of Obinutuzumab (GA101) plus CHOP Chemotherapy in First-Line Advanced Diffuse Large B-Cell Lymphoma: Results from the Phase 2 GATHER Study (GAO4915g).

DLBCL is an aggressive disease and the most common type of non-Hodgkin’s lymphoma, accounting for approximately 30% of cases. During or after first-line treatment, the authors noted between 35% and 40% of patients will relapse, while <25% of these patients are cured with second-line therapy. The combination of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] chemotherapy is the standard first-line treatment option and improves survival and other outcomes.

The FDA approved obinutuzumab in combination with chlorambucil in February for patients with previously untreated chronic lymphocytic leukemia. Obinutuzumab, an anti-CD20 monoclonal antibody, is administered via intravenous infusion. It is not approved for any other indication.

This study included adult patients with untreated CD-20 positive DLBCL, a life expectancy of at least 12 months, Ann Arbor stage 2, 3, or 4 disease, and an International Prognostic Index of 2 or higher with at least 1 bidimensionally measurable lesion. Eighty patients enrolled, and 69 completed treatment.

They received 8 cycles of obinutuzumab: 1000 mg on day 1 of each 21-day cycle plus additional doses on days 8 and 15 of cycle 1. They also took CHOP chemotherapy on day 1 of cycles 1 through 6. Patients were strongly recommended to take prophylactic granulocyte-colony stimulating factor (G-CSF) during cycle 1 and were allowed to receive G-CSF after cycle 1.

Nineteen doses of obinutuzumab were skipped, all in cycle 1. The combination treatment was delayed by ≥5 days in 3.8% of patients in cycle 2, 9% of patients in cycle 3, 10.3% of patients in cycle 4, 6.5% of patients in cycle 5, and 9.5% of patients in cycle 6.

Each patient had at least 1 adverse event, and 77.5% of adverse events were considered related to obinutuzumab. In addition, 58.8% of patients had a grade 3 or higher adverse event, and 63.8% of patients had infusion-related adverse events. The most common grade 3 or higher adverse events were neutropenia, febrile neutropenia, and anemia. Furthermore, 32.5% of patients had a serious adverse event: 8.8% were related to obinutuzumab and 5% led to treatment withdrawal.

After receiving treatment, 55% of patients had a complete response, 27.5% had a partial response, and 11.3% had progressive disease. According to an independent review, 60% of patients had a complete response, 18.8% had a partial response, and 11.3% had progressive disease.

This study was sponsored by Genentech.