Results of the phase 3 GADOLIN trial have revealed a new treatment option for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to researchers.
The trial showed that obinutuzumab plus bendamustine, followed by obinutuzumab maintenance, can ward off disease progression in NHL patients who have relapsed after rituximab-based
therapy or stopped responding to it.
The obinutuzumab regimen significantly improved progression-free survival (PFS) when compared to bendamustine alone (without maintenance).
However, there was no significant difference between the 2 treatment arms with regard to overall survival (OS).
Still, the trial was stopped before its protocol-specified final analysis because of the PFS benefit in the obinutuzumab arm.
Laurie Sehn, MD, of the BC Cancer Agency in Vancouver, British Columbia, Canada, and her colleagues reported the results of this trial in The Lancet. The research was funded by F. Hoffmann-La Roche Ltd.
Patients and treatment
GADOLIN enrolled patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and Waldenstrom’s macroglobulinemia (WM).
The patients were randomized to receive one of the following treatments:
- bendamustine alone (120 mg/m2/day on days 1 and 2 for up to six 28-day cycles)
- bendamustine (90 mg/m2/day on days 1 and 2 for up to six 28-day cycles) plus obinutuzumab (1000 mg on days 1, 8, and 15 for cycle 1, followed by 1 dose for up to six 28-day cycles), followed by obinutuzumab maintenance (1000 mg every 2 months for 2 years or until progression).
The investigators said baseline characteristics were well-balanced between the treatment arms. Patients in both arms had received a median of 2 prior treatments, and the median time from last treatment was about 4 months.
Of the 194 patients randomized to the obinutuzumab arm, 155 had FL, 27 had MZL, and 12 had SLL. Of the 202 patients randomized to the bendamustine (control) arm, 166 had FL, 19 had MZL, 16 had SLL, and 1 had WM.
Ultimately, 156 patients completed induction in the obinutuzumab arm, as did 129 patients in the control arm. Thirty-six patients completed maintenance with obinutuzumab, and 46 were still receiving maintenance at the time of analysis.
The median follow-up was 21.9 months in the obinutuzumab arm and 20.3 months in the control arm.
Safety
Nearly all patients in both arms experienced at least 1 adverse event (AE).
Grade 3-5 AEs occurred in 68% of patients in the obinutuzumab arm and 62% in the control arm. The most frequent of these were neutropenia (33% vs 26%), thrombocytopenia (11% vs 16%), anemia (8% vs 10%), and infusion-related reactions (11% vs 6%).
Serious AEs occurred in 38% of patients in the obinutuzumab arm and 33% in the control arm. The most common were febrile neutropenia (4% vs 3%), infusion-related reactions (4% vs 2%), and pneumonia (3% vs 5%).
Response
According to an independent review committee, the overall response rate at the end of induction was 69% in the obinutuzumab arm and 63% in the control arm. The complete response rates were 11% and 12%, respectively.
The median duration of response was not reached in the obinutuzumab arm and was 13.2 months in the control arm.
Survival
The median PFS was not reached in the obinutuzumab arm and was 14.9 months in the control arm (P=0.0001), according to the independent review committee.
According to investigators, the median PFS was 29.2 months and 14 months, respectively (P<0.0001).
At last follow-up, the median OS had not been reached in either arm (P=0.40).
There were 34 deaths in the obinutuzumab arm and 41 in the control arm (18% and 20%, respectively). Most patients died of disease progression (65% and 71%, respectively).
Twelve patients in each arm (6%) died of AEs. Three of these deaths were treatment-related in the obinutuzumab arm (acute myeloid leukemia, vascular pseudoaneurysm, and pseudomonal sepsis).
Five of the 12 AE deaths in the control arm were treatment-related (sepsis, 2 cases of leukemia, and 2 cases of Pneumocystis jirovecii pneumonia).
Taking these results together, the investigators said the obinutuzumab regimen had a manageable toxicity profile, and it produced a “clinically meaningful and significant” improvement in PFS when compared to bendamustine alone.
