Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study

Abstract

Background: Bendamustine was approved in China on May 26th, 2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma (NHL). The current study was the registration trial and the first reported evaluation of the efficacy, safety, and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment. Methods: This was a prospective, multicenter, open-label, single-arm, phase 3 study (NCT01596621; C18083/3076) with a 2-year follow-up period. Eligible patients received bendamustine hydrochloride 120 mg/m 2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles (and up to eight cycles). The primary endpoint was the overall response rate (ORR); and secondary endpoints were duration of response (DoR), progression-free survival (PFS), safety, and pharmacokinetics. Patients were classified according to their best overall response after initiation of therapy. Proportions of patients in each response category (complete response [CR], partial response [PR], stable disease, or progressive disease) were summarized along with a two-sided binomial exact 95% confidence intervals (CIs) for the ORR. Results: A total of 102 patients were enrolled from 20 centers between August 6th, 2012, and June 18th, 2015. At the time of the primary analysis, the ORR was 73% (95% CI: 63%–81%) per Independent Review Committee (IRC) including 19% CR and 54% PR. With the follow-up period, the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment; the median PFS was 18.6 months and 15.3 months, respectively. The most common non-hematologic adverse events (AEs) were gastrointestinal toxicity, pyrexia, and rash. Grade 3/4 neutropenia was reported in 76% of patients. Serious AEs were reported in 29 patients and five patients died during the study. Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities. Conclusion: Bendamustine is an active and effective therapy in Chinese patients with relapsed, indolent B-cell NHL, with a comparable risk/benefit relationship to that reported in North American patients. Clinical trial registration: ClinicalTrials.gov, No. NCT01596621; https://clinicaltrials.gov/ct2/show/NCT01596621

Clinical Efficacy of Bendamustine Plus Rituximab (BR) for B-cell Relevant Indolent Non-Hodgkin’s Lymphoma and Role of β2-MG in Predicting the Efficacy of BR Regimen: A Real-World Retrospective Study in China

“…Further clarification of the pharmacological mechanism of bendamustine in antitumor may unveil differences in clinical benefits between R-CHOP and BR regimens in the management of B-cell-associated iNHL. A prospective, multicenter, open-label, single-arm, phase 3 study demonstrated the efficacy and safety of bendamustine in Chinese adults with indolent B-cell NHL who relapsed after chemotherapy and rituximab treatment, with results similar to those of previous clinical trials conducted in patients from Western countries [ 23 ], which seems to be in line with our results. It is worth noting that the average PFS and OS of the patients in this study were 12.1 months and 15.5 months, respectively, which remains various from the results obtained in the above prospective study.…”

Agents contributing to secondary immunodeficiency development in patients with multiple myeloma, chronic lymphocytic leukemia and non-Hodgkin lymphoma: A systematic literature review

“…These analyses did not include B-lineage monoclonal antibodies, tyrosine kinase inhibitors, proteasome inhibitors, or IMiDs. Non-specific agents were used in eight studies, one in CLL ( 65 ), two in MM ( 79 , 82 ), and five in NHL ( 102 , 115 , 116 , 119 , 129 ). In CLL, the proportion of patients with any grade and grade ≥3 infections was 45.8% and 11.9%, respectively.…”

“…In patients treated with kinase monotherapy, sinopulmonary bacterial infections were reported in 8.0% of patients with CLL ( 51 , 60 , 62 ). In those patients who received non-specific agents as monotherapy and/or double/triplet regimen, sinopulmonary bacterial infections were reported in 9.9% ( 102 , 115 , 116 , 119 , 129 ) of patients with NHL.…”