CHICAGO—Obinutuzumab, a new anti-CD20 monoclonal antibody, significantly delayed progression of indolent non-Hodgkin lymphoma (iNHL) when added to standard bendamustine chemotherapy, according to interim results from the phase III GADOLIN trial. Laurie H. Sehn, MD, MPH, from BC Cancer Agency, Vancouver, British Columbia, presented the findings during a presentation at the 2015 ASCO Annual Meeting.
The standard initial treatment for iNHL is a combination of chemotherapy and the targeted drug rituximab; however, many patients ultimately become resistant to rituximab, leaving them with limited options for further treatment.
“Unfortunately, there is not yet a cure for indolent lymphoma, so the overall goal of treatment is to increase the amount of time patients remain symptom-free and in remission,” Dr. Sehn said. “The fact that this new approach doubled average remission time marks a major step forward for our patients.”
To determine the benefit of obinutuzumab plus standard bendamustine chemotherapy in these rituximab-refractory patients, GADOLIN investigators studied the outcomes of 396 patients with various types of NHL – the most common being follicular lymphoma. Baseline characteristics were similar between the two treatment arms, with patients having a median of two prior therapies and approximately four months had elapsed since their last treatment. More than 90 percent of patients in each arm were refractory to their last treatment, Dr. Sehn added.
Patients were randomized to receive either:
- bendumustine 120 mg/m2 (n=194) for a maximum of six 28-day cycles
- bendamustine 90 mg/m2 plus 1,000 mg obinutuzumab (n=202) for a maximum of six 28-day cycles, followed by obinutuzumab single-agent therapy every two months for two years
After a median observation time of 20 months in the bendamustine group and 22 months in the combo group, Dr. Sehn and colleagues found that the median PFS was doubled in the obinutuzumab group (TABLE). After the primary endpoint (progression-free survival assessed by an independent radiology facility) was reached, the study was unblinded.
|TABLE. Progression-free survival among GADOLIN participants|
|Bendamustine + obinituzumab||
0.55 (95% CI 0.4-0.74; p=0.00011
0.52 (95% CI 0.39-0.70; p<0.0001)
The GADOLIN investigators saw no new or unexpected side effects or safety concerns in the combination arm, although rates of grade ≥3 neutropenia and infusion-related reactions were slightly more frequent in the combination arm than the bendamustine arm (68% vs. 62.1% and 33.0% vs. 26.3%, respectively). However, patients in the bendamustine-alone arm did experience greater rates of grade ≥3 thrombocytopenia (16.2% vs. 10.8%), anemia (10.1% vs. 7.7%), and pneumonia (5.6% vs. 2.6%).
“This study is remarkable because it demonstrates the first randomized evidence of a clinical benefit of a novel anti-CD20 monoclonal antibody for patients who are rituximab-refractory,” Dr. Sehn said. Obinutuzumab, in combination with chlorambucil, is currently FDA-approved for the treatment of chronic lymphocytic leukemia. The findings from the phase III GADOLIN trial could support a new indication for obinutuzumab.
“Obinutuzumab may offer patients the chance to stay well for a significantly longer period of time, putting off the need for additional chemotherapy,” Dr. Sehn said, however, longer follow-up is needed to determine obinutuzumab’s potential overall survival benefit.
Source: Sehn LH, Chua NS, Mayer J, et al. GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma. Abstract #LBA8502. Presented at the 2015 American Society of Clinical Oncology Annual Meeting. Chicago, IL, June 1, 2015.