Safety and efficacy of obinutuzumab in Chinese patients with B-cell lymphomas: a secondary analysis of the GERSHWIN trial

Yan Qin, Yuqin Song, Zhixiang Shen, Xin Du, Wei Ji, Wanling Hsu, Jun Zhu, Yuankai Shi, Yan Qin, Yuqin Song, Zhixiang Shen, Xin Du, Wei Ji, Wanling Hsu, Jun Zhu, Yuankai Shi

Abstract

Background: Patients with relapsed/refractory B-cell lymphomas have limited treatment options. GERSHWIN is an open-label, single-arm, phase Ib study of obinutuzumab monotherapy in Chinese patients with histologically documented CD20+ relapsed/refractory chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), or follicular lymphoma (FL). The primary outcome measure of pharmacokinetics has been previously reported. We now present data on the secondary endpoint measures (e.g., safety, and efficacy and pharmacodynamics).

Methods: Patients received 1000 mg obinutuzumab intravenously on days 1, 8, and 15 of cycle 1 (CLL patients; first dose split over 2 days), and on day 1 of cycles 2-8. Each cycle lasted for 21 days; the treatment period was 24 weeks. All subjects receiving at least one dose of obinutuzumab were included in the analysis of safety, efficacy, as well as pharmacodynamics.

Results: A total of 48 patients (> 18 years of age) were enrolled (CLL: 12; DLBCL: 23; FL: 13). The subjects received a median of two lines of anticancer treatment prior to the enrollment. Thirty-five patients (72.9%) had at least one adverse event (AE). The most frequent AE was infusion-related reactions (15 patients; 31.3%), followed by pyrexia (11 patients; 22.9%). Treatment-related AEs were reported in 28 patients (58.3%), and included one death (interstitial lung disease). End-of-treatment (EoT) response rate was 33.3%. Best overall response rate was 47.9%. Most CLL patients achieved a partial response at EoT (58.3%). CD19+ depletion occurred in 75.0% of the patients with CLL, and all patients with FL and DLBCL.

Conclusions: The safety and efficacy of obinutuzumab monotherapy in Chinese patients with B-cell lymphomas were similar to that observed in previous studies in non-Chinese patients; no new safety signals were observed. Clinical trial registration ID NCT01680991.

Keywords: B-cell lymphoma; Chinese patients; Chronic lymphocytic leukemia; Obinutuzumab.

Figures

Fig. 1
Fig. 1
Patient flow through the study. aReasons for screening failures: three patients tested positive for Hepatitis B core antibody, two patients did not meet inclusion criteria number 1 (histologically documented CD20+ malignant disease), one patient did not meet inclusion criteria number 2 (relapsed/refractory CLL, FL, or DLBCL), one patient had positive hepatitis serology, and one patient had a hemoglobin value of 56 g/L. bReasons for discontinuation during treatment: AE (pneumonia), n = 1; PD, n = 9; protocol violation, n = 1; withdrawal by the patient, n = 3; physician decision, n = 6. cReasons for discontinuation during follow-up: death, n = 2; withdrawal by the patient, n = 4; PD, n = 1; physician decision, n = 2; other, n = 2 (patient could not visit due to poor physical condition, progression of disease confirmed in another hospital). CLL chronic lymphocytic leukemia, DLBCL diffuse large B-cell lymphoma, FL follicular lymphoma

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