Safety, tolerability and pharmacokinetics of shorter duration of infusion of obinutuzumab in Japanese patients with B-cell non-Hodgkin lymphoma: Final results of the phase II GATS study

Background: Shorter duration of infusion of monoclonal antibody treatments May reduce treatment burden and improve healthcare resource utilization. Methods: This phase II study recruited Japanese patients with previously untreated CD20+ B-cell non-Hodgkin lymphoma. Patients received intravenous obinutuzumab 1000 mg by regular infusion on Days 1, 8 and 15 of Cycle 1, followed by 90-min shorter duration of infusion in up to seven subsequent cycles, provided they received ≥3 regular infusions without any grade ≥3 infusion-related reactions and had a lymphocyte count <5.0 × 10⁹ cells/l. Standard cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy was given in Cycles 1–6. The primary endpoints were as follows: incidence of grade ≥3 infusion-related reactions in Cycle 2 in patients who started shorter duration of infusion in Cycle 2, serum obinutuzumab concentrations and phar-macokinetic parameters and the time course of cytokine release. Adverse events and serious adverse events were monitored. Results: Of 35 patients treated, 28 completed eight cycles; 31 started shorter duration of infusion in Cycle 2 and two patients in subsequent cycles. Two patients discontinued before starting shorter duration of infusion. No grade ≥3 infusion-related reactions occurred in Cycle 2. Twenty-one infusion-related reactions (all grades 1–2) were reported in 17/35 (49%) patients overall, mostly in Cycle 1 (18/21 infusion-related reactions [86%]). Grade ≥3 AEs occurring in ≥10% of patients included neutropenia/neutrophil count decreased (66%) and leukopenia/white blood cell count decreased (23%). Steady-state pharmacokinetics of obinutuzumab were attained in Cycle 2 and were not affected by shorter duration of infusion. No relevant cytokine elevations were reported with shorter duration of infusion. Conclusions: Regular infusion and shorter duration of infusion of obinutuzumab have comparable tolerability and pharmacokinetics in Japanese patients.