Obinutuzumab May Have Synergistic Action With New Tyrosine Kinase Inhibitors

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Final results from the phase I/II GAUGUIN study showed that obinutuzumab (Gazyva) monotherapy was active in patients with heavily pretreated relapsed or refractory chronic lymphocytic leukemia, European researchers reported in Blood. In phase II, median progression-free survival was 10.7 months, and median duration of response was 8.9 months.

“For clinical use, obinutuzumab monotherapy is likely to be suitable in situations where rituximab [Rituxan] or ofatumumab [Arzerra] monotherapy are currently used, due to its higher propensity for B-cell depletion, and in patients not suitable for cytotoxic chemotherapy,” the researchers wrote. “However, arguably the most exciting development for obinutuzumab will lie in its potential for combination with new kinase inhibitors such as ibrutinib [Imbruvica] or idelalisib [Zydelig], where its efficiency with regard to eliminating circulating B cells may be synergistic with the strong ability of such kinase inhibitors to induce the migration of clonal cells from lymph node and bone marrow to the blood.”

During the phase I dose escalation portion of the study, 13 patients from 7 centers across France received obinutuzumab at 400 to 1,200 mg (days 1 and 8 of cycle 1; day 1 of cycles 2–8). In the phase II portion, 20 patients from 20 centers across France and Germany received a fixed dose of 1,000 mg (days 1, 8, and 15 of cycle 1; day 1 of cycles 2–8). The median ages of the patients were 64 in phase I and 62.5 in phase II. The median number of previous treatments was three for patients in both phases of the study. Ten patients (50%) in phase II had received prior rituximab treatment.

The overall end-of-treatment response rates (all partial responses) were 62% in phase I and 15% in phase II, and the respective best overall response rates were 62% and 30%. The researchers speculated that lower best overall response in phase II was “possibly due to higher baseline tumor burden resulting in lower treatment exposure.”

Nearly all patients had infusion-related reactions, although few were grade 3/4. Adverse events were independent of dose, and no dose-limiting toxicities were reported. ■

Cartron G, et al: Blood 124:2196-2202, 2014.




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