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Lenalidomide plus obinutuzumab demonstrates antitumor activity in relapsed follicular B-cell lymphoma
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Oral lenalidomide in combination with obinutuzumab appeared well tolerated and effective for the treatment of relapsed or refractory follicular B-cell lymphoma, according to results from the GALEN clinical trial.
Researchers established a recommended dose of 20 mg lenalidomide (Revlimid, Celgene) in combination with 1,000 mg obinutuzumab (Gazyva, Genentech) for investigation in a phase 2 clinical trial.
“In this first clinical study of combined obinutuzumab and lenalidomide given for 6 months, an acceptable safety and tolerability profile was found in patients with relapsed or refractory follicular lymphoma,” Franck Morschhauser, MD, of Centre Hospitalier Régional Universitaire de Lille in France, and colleagues wrote.
“There was no signal of increased incidence or more severe infusion-related reactions, thromboembolic events or thrombocytopenia,” they added.
Previous research has shown that lenalidomide generated natural killer cell activation in vivo, which further improved the efficacy of subsequent obinutuzumab infusion therapy.
“Thus, combining obinutuzumab with lenalidomide may be even more effective than rituximab plus lenalidomide,” the researchers wrote.
The analysis included 19 patients aged at least 18 years (mean age, 61.5 years; 50% women) with relapsed or refractory follicular lymphoma after rituximab (Rituxan; Genentech, Biogen)-based therapy.
Patients received escalating doses of daily oral lenalidomide at 10 mg (n = 7), 15 mg (n = 3), 20 mg (n = 6) and 25 mg (n = 3) on days 1 to 21 of cycle 1 and on days 2 to 22 of cycles 2 to 6, in 28-day cycles. Researchers performed dose escalation in a 3 + 3 design based on dose-limiting toxicity during cycle 1 to establish the maximum tolerated dose.
Patients also received 1,000 mg IV obinutuzumab on days 8, 15 and 22 during cycle 1 and on day 1 during cycles 2 to 6.
Establishing a recommended phase 2 dose of lenalidomide in combination with a fixed dose of obinutuzumab served as the study’s primary endpoint. Secondary endpoints included safety, tolerability and preliminary antitumor activity.
Median follow-up for the final analysis was 38.1 months (95% CI, 35-41.6).
Twelve patients (63.2%; 95% CI, 38.4-83.7) responded to treatment after six cycles. Of those who responded, eight had a complete response, three had unconfirmed complete response and one had a partial response.
At 3 years, 52.1% (95% CI, 28.0-71.6) of patients achieved PFS and 73.3% (95% CI, 47.2-87.9) achieved OS.
All patients experienced at least one adverse event. There were 164 adverse events overall, the most common of which included constipation (52.6%), neutropenia (47.4%) and asthenia (36.8%). Most events were grade 1 or grade 2 (n = 139).
Of grade 3 or grade 4 adverse events, 64.3% were neutropenia/neutrophil decrease, but there were no cases of febrile neutropenia.
Four dose-limiting toxicities occurred among two patients, but researchers deemed these unrelated to treatment and the maximum tolerated dose was not reached.
Thirteen (7.9%) adverse events were related only to obinutuzumab, 54 (32.9%) were related only to lenalidomide and 32 (19.5%) were related to the combination.
“In the small group of patients reported here, of whom 40% where rituximab refractory and 20% refractory to last prior therapy, the GALEN regimen showed promising efficacy compared with a report of lenalidomide plus rituximab,” researchers wrote. – by Melinda Stevens
Disclosures: Celgene and Roche supported this study. Morschhauser reports personal fees from Bristol-Myers Squibb, Celgene, Epizyme, Gilead, Janssen, Servier and Roche for consultant/advisory board roles or scientific lectures unrelated to the study. Please see the study for all other authors’ relevant financial disclosures.
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