Obinutuzumab New Option for Rituximab-Refractory Indolent NHL

Combination treatment with the anti-CD20 monoclonal antibody obinutuzumab plus bendamustine followed by obinutuzumab maintenance significantly delayed disease progression in patients with indolent non-Hodgkin lymphoma refractory to rituximab compared with bendamustine therapy alone, according to results of an interim analysis of the GADOLIN trial published in Lancet Oncology.

“The results of this study showed that patients receiving obinutuzumab plus bendamustine had a significant improvement in independent review committee–assessed progression-free survival compared with bendamustine monotherapy, and the median progression-free survival for obinutuzumab plus bendamustine has not yet been reached,” wrote researchers led by Laurie H. Sehn, MD, of the British Columbia Cancer Agency and University of British Columbia, Vancouver.

Patients with indolent non-Hodgkin lymphoma have few treatment options if their disease is refractory to rituximab-based treatment regimens. This trial enrolled 396 patients with indolent, CD20-positive disease and randomly assigned them to treatment with the combination obinutuzumab plus bendamustine (n = 194) or bendamustine alone (n = 202). Patients in the combination arm who did not progress continued on obinutuzumab maintenance for up to 2 years.

At the first interim analysis, an Independent Data Monitoring Committee stopped the trial early when the primary endpoint had been met. At the time of the analysis, progression-free survival events occurred in 37% of patients in the combination group and 51% of the monotherapy group.

With a median follow-up of more than 20 months, the median progression-free survival had not yet been reached for patients assigned to obinutuzumab plus bendamustine compared with 14.9 months for bendamustine alone (hazard ratio [HR], 0.55 [95% CI, 0.40-0.74] P = .0001). According to the researchers, “the HR is comparable to the benefit previously shown with the addition of rituximab to chemotherapy in rituximab-naive patients.”

Although the study was not powered to detect a significant difference, combination therapy produced longer progression-free survival in most of the analyzed subgroups compared with monotherapy. At the interim analysis, there was no significant difference in overall survival between the two groups.

Grade 3 to grade 5 adverse events occurred in more than 60% of patients in the combination arm (68%) and the monotherapy arm (62%). The most common grade 3 or worse adverse events were neutropenia, thrombocytopenia, anemia and infusion-related reactions. Thirty-eight percent of patients in the combination arm and 33% of patients in the monotherapy arm had a serious adverse event; deaths due to serious adverse events occurred in 6% of patients on both arms.

“In conclusion, this randomized phase III study is, to our knowledge, the first to show the clinical use of a novel anti-CD20 monoclonal antibody for patients with indolent non-Hodgkin lymphoma who are no longer benefiting from rituximab,” the researchers wrote. “The addition of obinutuzumab to bendamustine followed by obinutuzumab maintenance resulted in a clinically meaningful and significant improvement in progression-free survival compared with bendamustine monotherapy, with a manageable toxicity profile.”