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.

Abstract

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 pharmacokinetic 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.

• Authors: Ken Ohmachi, Kiyoshi Ando, Tomohiro Kinoshita, Kyoya Kumagai, Kiyohiko Hatake, Takayuki Ishikawa, Takanori Teshima, Koji Kato, Koji Izutsu, Eisuke Ueda, Kiyohiko Nakai, Hiroshi Kuriki, Kensei Tobinai
• Journal: Japanese journal of clinical oncology (Jpn J Clin Oncol) Vol. 48 Issue 8 Pg. 736-742 (Aug 01 2018) ISSN: 1465-3621 [Electronic] England
• PMID: 30060000 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)

Chemical References

• Antibodies, Monoclonal, Humanized
• Cytokines
• obinutuzumab

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects, pharmacokinetics)
• Area Under Curve
• B-Lymphocytes (pathology)
• Cytokines (metabolism)
• Endpoint Determination
• Female
• Humans
• Infusions, Intravenous
• Lymphoma, Non-Hodgkin (drug therapy)
• Male
• Middle Aged
• Treatment Outcome