Combination treatment with lenalidomide 20 mg and obinutuzumab 1,000 mg was effective and well-tolerated in patients with relapsed or refractory follicular B-cell lymphoma, according to the results of a phase Ib study.
“To further explore the optimal duration of this combination, the phase II part of this study is currently assessing efficacy of the GALEN regimen with a lenalidomide dose of 20 mg during 6 months and 2 years of maintenance in three separate populations,” Franck Morschhauser, of Centre Hospitalier Regional Universitaire de Lille, France, and colleagues wrote in Blood.
Previous research had shown promising results with the combination of rituximab and lenalidomide. Obinutuzumab is a type II anti-CD20 monoclonal antibody that is considered to better enhance antibody-dependent cellular cytotoxicity compared with rituximab.
In the study, Morschhauser and colleagues enrolled 20 patients aged 18 years or older with relapsed or refractory follicular lymphoma who had already been treated with a rituximab-containing regimen. One patient withdrew early due to neutropenia at baseline screening.
Patients received escalating doses of oral lenalidomide (10 mg to 25 mg). Obinutuzumab 1,000 mg was given on days 8, 15, and 22 for the first cycle and on day 1 for subsequent cycles, up to 6 cycles total.
Overall, 164 adverse events occurred, the majority of which were grade 1 or 2. The most common events were constipation (52.6%), neutropenia (47.4%), and asthenia (36.8%). The most common grade 3 or 4 events were neutropenia/neutrophil decrease (64.3%).
The researchers observed four dose-limiting toxicities (DLTs), occurring in two patients. One death occurred due to cardiac arrest in the presence of grade 3 worsening pleural effusion, and one grade 3 pulmonary infection occurred with grade 3 hypokalemia. Both cases were considered unrelated to study treatment. No maximum tolerated dose was reached, but the recommended phase II dose was 20 mg because of grade 3/4 neutropenia that occurred at 25 mg.
Nine serious adverse events occurred in 7 patients, including 3 (33.3%) second primary malignancies. The researchers wrote that although these could be related to study treatment, “both patients had received heavy prior therapy that could have contributed to their emergence.”
The majority of patients in the study responded to treatment (63.2%). Among the responses were eight complete responses, three unconfirmed complete responses, and one partial response. The median follow-up was 38.1 months. At 3 years, the progression-free survival rate was 52.1%, and the overall survival rate was 73.3%.
“In the small group of patients reported here, of whom 40% were rituximab refractory and 20% refractory to last prior therapy, the GALEN regimen showed promising efficacy compared with a report of lenalidomide plus rituximab,” the researchers wrote. “Our data are consistent with the preliminary report of another phase I study that combined obinutuzumab and lenalidomide using a slightly different initial treatment schedule (no 8 days of lenalidomide prophase and a longer induction period of 12 months); no DLTs were observed at the highest dose of 20 mg, which was selected as the RP2D [the highest dose with acceptable toxicity].”