A phase I/II study of 10-min dosing of bendamustine hydrochloride (rapid infusion formulation) in patients with previously untreated indolent B-cell non-Hodgkin lymphoma, mantle cell lymphoma, or relapsed/refractory diffuse large B-cell lymphoma in Japan

Abstract

Purpose This phase I/II clinical study was conducted to examine the safety, tolerability, pharmacokinetics, and efficacy of 10-min dosing of bendamustine in patients with previously untreated indolent B-cell non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL) (Group 1) and patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) (Group 2). Methods Rituximab 375 mg/m2 was administered intravenously every 28 days to Group 1 patients on day 1 and every 21 days to Group 2 patients on day 1. Bendamustine 90 mg/m2/day was administered to the former on days 1 and 2; bendamustine 120 mg/m2/day was administered to the latter on days 2 and 3. Each regimen was delivered up to six cycles for both groups. The primary endpoints were safety and tolerability in Groups 1 and 2, respectively. Results Among 37 enrolled patients, safety was assessed in 36. In Group 1 (n = 30), 27 patients (90%) had follicular lymphoma. Adverse events (AEs) were observed in all 30 patients in Group 1. Dose-limiting toxicities were observed in two of six patients in Group 2. Common AEs included lymphocyte count decreased (86.7%, 100%). In Group 1, overall response and complete response rates were 93.1% (95% confidence interval [CI] 77.2–99.2%) and 75.9% (95% CI 56.5–89.7%), respectively. The Cmax and AUC of bendamustine tended to be higher in Group 2 than in Group 1. Conclusions This study showed that bendamustine is safe, well-tolerated and effective for patients with previously untreated iNHL, MCL or rrDLBCL. Pharmacokinetic data were equivalent to those obtained outside of Japan. Registration numbers Registration NCT03900377; registered April 3, 2019.

Comprehensive scientometrics and visualization study profiles lymphoma metabolism and identifies its significant research signatures

“…Recently, the efforts of oncology biologists and clinicians yielded considerable essential research advances in this field, and the development of new drugs has been flourishing. Novel agents, such as BTK inhibitors, BCL2 inhibitors, PD-1 monoclonal antibodies, and epigenetic agents, such as Decitabine, Azacitidine, and Cidabenamide, have demonstrated promising efficacy and a manageable safety profile in patients with primary or relapsed refractory lymphoma, either alone or in combination with CHOP or R-CHOP regimens (10)(11)(12)(13)(14)(15). Multiple novel immunotherapeutic agents, such as bispecific antibodies and chimeric antigen receptor T-cells, have also shown potential efficacy, introducing novel treatment alternatives for patients who otherwise have no possibility of cure (16).…”