Comparison of efficacy and safety of BR regimen and R-CHOP regimen in the treatment of newly diagnosed follicular lymphoma / 中国综合临床

Objective:Compare the clinical efficacy and safety of bendamustine combined with rituximab (BR regimen) and rituximab combined with standard CHOP regimen (R-CHOP regimen) in the treatment of newly diagnosed follicular lymphoma (FL).Methods:Adopting a prospective case-control study method. 104 newly diagnosed FL patients admitted to Beijing Aerospace General Hospital from January 2018 to January 2022 were selected and randomly divided into an observation group and a control group using a random number table method, with 52 patients in each group. The observation group was treated with bendamustine combined with rituximab, while the control group was treated with rituximab combined with standard CHOP regimen. Both groups were treated for 6 consecutive courses of treatment, with a 21 day treatment period. Compare the serum lactate dehydrogenase (LDH) levels before and after treatment between two groups β 2-Microglobulin (β 2-microglobulin, β 2-MG level, improvement in quality of life after treatment, long-term survival, clinical efficacy, and incidence of adverse reactions. Measurement data is represented by paired t-tests for intra group comparisons, and independent sample t-tests for inter group comparisons; Counting data is represented as an example (%), and inter group comparisons are made using χ 2-test, Wilcoxon rank sum test was used for comparing rank data. Survival analysis was conducted using the Log Rank test. Results:After treatment, serum LDH and The levels of β 2-MG were lower than before treatment [LDH: (262.34±37.24) U/L ratio (323.45±44.46) U/L, (287.23±43.19) U/L ratio (318.28±52.35) U/L; β 2-MG: (2.72±0.30) mg/L compared to (3.45±0.37) mg/L, (2.93±0.28) mg/L compared to (3.37±0.42) mg/L, t-values of 7.60, 3.30, 11.05, 6.29, P values of <0.001, 0.001, <0.001, <0.001, <0.001], and the observation group was lower than the control group ( t-values of 3.15, 3.69, P values of 0.002, <0.001, respectively). After 6 courses of treatment, the quality of life in the observation group improved in 27 cases, stabilized in 22 cases, and decreased in 3 cases; The quality of life in the control group improved in 18 cases, stabilized in 26 cases, and decreased in 8 cases. The improvement of quality of life in the observation group was better than that in the control group ( Z=-2.03, P=0.042). The progression free survival period in the observation group was longer than that in the control group [52.53 months (95% confidence interval: 49.16-55.89 months) compared to 38.84 months (95% confidence interval: 32.44-45.24 months)], and the difference was statistically significant (Log Rank χ 2=4.06, P=0.044), there was no statistically significant difference in overall survival between the two groups ( P=0.217). The complete remission rate in the observation group was higher than that in the control group [88.46%(46/52) vs 71.15%(37/52)], χ 2=4.83, P=0.028], there was no statistically significant difference in objective response rates between the two groups ( P=0.485). The incidence of nausea, vomiting, leukopenia, neutropenia, alopecia, and fatigue in the observation group was lower than that in the control group, and the differences were statistically significant (all P<0.05). Conclusions:Both the BR regimen and R-CHOP regimen can significantly reduce serum tumor marker levels in the treatment of newly diagnosed FL. However, the BR regimen has a higher complete response rate, better patient quality of life, longer PFS, fewer toxic side effects, and more significant overall efficacy.

Progress of bendamustine in treatment of multiple myeloma / 白血病·淋巴瘤

Bendamustine, a bifunctional derivate of nitrogen mustard, is an attractive treatment option for multiple myeloma (MM) due to its specific mode of activity, favorable toxicity profile, and clinical activity in patients resistant to alkylating agent. Bendamustine single agent and its combination with immunomodulators or proteasome inhibitors have been widely used in the relapsed/refractory MM patients. Bendamustine has brought the longer progression-free survival, overall survival time and deeper remission in the autologous stem cell transplantation pre-conditioning for MM patients. This paper reviews the treatment progress of bendamustine for MM.

Clinical reasearch of bendamustine combination regimen in the treatment of relapsed/refractory multiple myeloma / 中国医师杂志

Objective:To investigate the clinical efficacy and safety of bendamustine combination regimen in the treatment of patients with relapsed or refractory multiple myeloma (RRMM).Methods:From March 2020 to December 2020, 16 patients with RRMM were treated with bendamustine combination regimen in Beijing Jishuitan Hospital. The efficacy and adverse events (AEs) of bendamustine combination regimen were retrospectively analyzed in the 16 patients.Results:The median treatment lines for 16 patients with RRMM who received bendamustine combination regimen was 4 lines, and the median course of treatment was 3 (1-8). The median follow-up time after bendamustine treatment started was 5.3(1.3-9.2)months. Among the 16 cases, the disease control rate (DCR), overall response rate(ORR), and ≥ very good partial remission (VGPR) rate were 13/16, 5/16, 4/16 respectively. The median PFS was 4.9 months. Among them, the ORR of bendamustine combined with immunomodulators was higher. AEs were anemia, leukopenia, neutropenia, thrombocytopenia and fatigue. No patients who stopped treatment and adjusted the dose due to AEs.Conclusions:Bendamustine combination regimen is an effective and safe regimen for relapsed/refractory multiple myeloma.

Chinese expert consensus on bendamustine for the treatment of lymphoma (2020 version) / 白血病·淋巴瘤

Bendamustine, a bifunctionnal molecule with alkylating agent and antimetabolites properties, has shown a better efficacy in many pathological types of lymphomas. Many studies have shown the better efficacy of bendamustine with or without other agents in the treatment of lymphomas including indolent non-Hodgkin lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma. In 2008, bendamustine was approved by Food and Drug Administration of the United States for the treatment of patients with rituximab-resistant indolent non-Hodgkin lymphoma and chronic lymphocytic leukemia. However, bendamustine was not approved for the treatment of lymphomas in China unitil 2018, and most physicians had little clinical experience on the use of this agent. Based on the results of clinical trials of bendamustine in China and the relevant domestic and foreign literatures, the Chinese hematologists and oncologists developed the Chinese expert consensus on bendamustine for the treatment of lymphomas (2020 version).

Safety and efficacy of bendamustine in the conditioning regimen for autologous stem cell transplantation in patients with relapsed/refractory lymphoma

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.

Bendamustine, etoposide, and dexamethasone to mobilize peripheral blood hematopoietic stem cells for autologous transplantation in non-Hodgkin lymphoma

BACKGROUND: Bendamustine is a chemotherapeutic agent that has shown broad activity in patients with lymphoid malignancies. It contains both alkylating and nucleoside analog moieties, and thus, is not commonly used for stem cell mobilization due to concerns that it may adversely affect stem cell collection. Here we describe the lymphoma subset of a prospective, non-randomized phase II study of bendamustine, etoposide, and dexamethasone (BED) as a mobilization agent for lymphoid malignancies. METHODS: This subset analysis includes diffuse large B-cell lymphoma (N=3), follicular lymphoma (N=1), primary mediastinal B-cell lymphoma (N=1), and NK/T-cell lymphoma (N=1). Patients received bendamustine (120 mg/m² IV d 1, 2), etoposide (200 mg/m² IV d 1–3), and dexamethasone (40 mg PO d 1–4) followed by filgrastim (10 mcg/kg/d sc. through collection). RESULTS: We successfully collected stem cells from all patients, with a median of 7.9×10⁶/kg of body weight (range, 4.4 to 17.3×10⁶/kg) over a median of 1.5 days (range, 1 to 3) of apheresis. All patients who received transplants were engrafted using kinetics that were comparable to those of other mobilization regimens. Three non-hematologic significant adverse events were observed in one patient, and included bacterial sepsis (grade 3), tumor lysis syndrome (grade 3), and disease progression (grade 5). CONCLUSION: For non-Hodgkin lymphoma, mobilization with bendamustine is safe and effective.

Bendamustine in heavily pre-treated multiple myeloma patients: Results of a retrospective analysis from the Korean Multiple Myeloma Working Party

BACKGROUND: Bendamustine may be a potential treatment option for patients with myeloma, but little is known about the utility of bendamustine as a salvage treatment, especially in Asian patients. METHODS: We performed a multicenter retrospective study of patients with relapsed or refractory myeloma who received bendamustine and prednisone. RESULTS: The records of 65 heavily pre-treated patients, who had undergone bortezomib and lenalidomide treatment (median number of previous treatments: 5), were analyzed. The median time from diagnosis to bendamustine treatment was 3.8 years, and the median patient age was 63 years (range, 38‒77 yr). The responses to the last treatment before bendamustine were refractory disease (N=52, 80%) or disease progression from partial response (N=13, 20%). Twenty-three patients responded to the treatment, with an overall response rate of 35% (23/65), and the median number of bendamustine treatment cycles was two (range, 1‒5 cycles). The median overall survival after bendamustine treatment was 5.5 months and the overall survival rate in responders to bendamustine was significantly better than that in non-responders (P=0.036). CONCLUSION: Bendamustine may be a potential salvage treatment to extend survival in a select group of heavily pre-treated patients with relapsed or refractory myeloma.

Determination of Residual Palladium in Bendamustine Hydrochloride by GFAAS / 中国药师

Objective:To develop a method for the determination of palladium in bendamustine hydrochloride by GFAAS. Meth-ods:The sample was destroyed by heat, and the content of palladium was determined by GFAAS with the detection wavelength of 247. 6 nm. Results:The absorbance and the content of palladium showed a good linear relationship within the range of 20-60 ng· ml-1(r=0. 998 4). The average recovery of palladium was 102. 9%(RSD=1. 7%, n=9). Conclusion: The method is sensitive and simple, which can be used for the determination of palladium in bendamustine hydrochloride.

Clinical application progress of bendamustine in lymphocytic malignancy / 白血病·淋巴瘤

Bendamustine hydrochloride is a bifunctional alkylating agent with clinical activity to a number of cancers.Bendamustine,an emerging nitrogen mustards anticancer agent,can improve tolerability without sacrificing clinical activity.Although bendamustine has been used widely for more than 40 years,it was not systematically studied in lymphoproliferative disorders until the 1990s.Bendamustine molecule is more stable than the molecules of other alkylators,and it can cause more extensive and more durable damage to DNA.Unlike other alkylating agents,primary targets of bendamustine are based on excision repair pathways rather than mismatch repair pathways,and it activates DNA damage stress responses,induces apoptosis,inhibits mitotic checkpoints,and induces mitotic catastrophe.This paper will review the role of bendamustine in chronic lymphoblastic leukemia(CLL),indolent non-Hodgkin's lymphoma (NHL),diffuse large B-cell lymphoma (DLBCL),mantle cell lymphoma (MCL),peripheral T-cell lymphoma (PTCL),and Hodgkin' s lymphoma (HL).

Identification of the related substances in bendamustine hydrochloride / 中国药科大学学报

@#In the HPLC analysis of bendamustine hydrochloride, two related substances(IMP01 and IMP02)were detected. These two related substances were identified by LC-MS/MS and their structural confirmation was unambiguously carried out by synthesis followed by characterization using Q-TOF/MS and NMR. Based on the spectral data, related substances IMP01 and IMP02 were characterized as 4-(1-methyl-5-morpholino-1H-benzo［d］imidazol-2-yl)butyric acid hydrochloride and 4-{1-methyl-5-［(2-chloroethyl)(2-hydroxyethyl)amino］-1H-benzo［d］imidazol-2-yl)} butyric acid hydrochloride, respectively. Bendamustine hydrochloride and its related substances were separated under the established LC-MS condition. HPLC is a useful method for the determination of the related substances in bendamustine hydrochloride. Results obtained are valuable for its manufacturing process and quality control.

Efficacy of bendamustine hydrochloride in patients with rituximab-refractory indolent B-cell non-Hodgkin's lymphoma：results from a phaseⅢmulticenter study / 中国肿瘤临床

Objective:To evaluate the efficacy and toxicity of single-agent bendamustine in patients with indolent B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab. Methods:Between April 2010 and April 2013, 100 patients with rituximab-refrac-tory indolent B-cell NHL from 8 institutions were enrolled. Bendamustine was administered at 120 mg/m2 on days 1 and 2 every 21 days for 6-8 cycles. The primary endpoint was the overall response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results:One hundred patients with a median age of 56 (rang-ing from 28 to 74) years were recruited in this clinical study. The total number of chemotherapy was 447 cycles, and the median number was 4 cycles. Ninety-three patients could be evaluated for efficacy. Fifteen patients (16.1%) had complete remission (CR), 52 (55.9%) had partial remission (PR), 22 (23.7%) had stable disease (SD), and 4 (4.3%) had progression disease (PD). The ORR and DCR were 72%and 95.7%, respectively. After a median follow-up of 26.6 months (ranging from 2 to 48.4 months), 59 patients (63.4%) had PD.The median PFS was 8.53 (95%CI:6.518-10.542) months, and PFS rate for 1 year was (40.6±5.3)%. Forty-eight patients (48%) had 3/4 grade adverse events, including leucopenia (26%), neutropenia (24%), and anemia (11%). Conclusion:Single-agent bendamustine produced a high rate of objective responses in patients with rituximab-refractory indolent B-cell NHL and could be one of the new op-tions for second-line treatment of these patients. The most common adverse event is hematologic toxicity.

Effect of bendamustine plus rituximab on relapsed extragastric mucosa-associated lymphoid tissue lymphoma / 白血病·淋巴瘤

Objective To investigate the rituximab plus bendamustine (R-Benda) therapeutic effect for relapsed extragastric mucosa-associated lymphoid tissue (MALT) lymphoma.Methods Ten patients (three females and seven males) with relapsed extragastric MALT lymphoma undergoing therapy with R-Benda were defined.Bendamustine was given at a dose of 90 mg/m2 on days 2 and 3 in nine patients and at 70 mg/m2 in one patient, while all received 375 mg/m2 rituximab on day 1.Results Nine patients received six courses of therapy,while one patient discontinued therapy after five courses for personal reasons, while one elderly patient had progressive disease after three courses.Tolerance of therapy was excellent, and all except one patient responded.Eight patients achieved the complete remission, one achieved the partial remission, and one patient progressed.Toxicities were mild and mainly hematological.After a median follow-up of 24 months (range, 5-43 months), 9 patients were alive.Conclusion R-Benda regime has high activity and good tolerance for patients with relapsed extragastric MALT lymphoma.

Bendamustine for Relapsed and Refractory Hodgkin Lymphomas: Four Cases and a Review of the Literature.

Aims: The management of relapsed/refractory Hodgkin lymphoma is challenging and new choices are needed. Brentuximab vedotin and bendamustine are two effective drugs in these cases. The aim of this study is to present the response to bendamustine after brentuximab failure. Study Design: Retrospective study evaluating the response to bendamustine in four cases with relapsed or refractory Hodgkin lymphoma. Place and Duration of Study: Cukurova University Faculty of Medicine Department of Oncology, between 2012 and 2014. Methodology: Clinical and metabolic responses to bendamustine in four cases with relapsed refractory Hodgkin lymphoma were evaluated. Informed consent was obtained from the patients. Bendamustine was used in four cases with very refractory Hodgkin lymphoma after Brentuximab failure. The dosage was 120 mg/M2 for two consecutive days in 4 weeks, without growth factor support. Results: Four cases with relapsed or refractory Hodgkin lymphoma were treated with bendamustine after brentuximab vedotin failure. Complete metabolic response was documented in two cases,one case did not respond and only short duration of response was determined in one case. Conclusion: Bendamustine is an effective and cost-effective choice in cases with relapsed/refractory Hodgkin lymphoma after brentuximab vedotin failure. However response is of short duration and definitive treatment must be performed as soon as possible.

Bendamustine hydrochloride in patients with rituximab-refractory indolent B-cell non-Hodgkin's lymphoma / 中国肿瘤临床

Objective:To observe the clinical efficacy and toxicities of bendamustine hydrochloride in patients with rituximab-re-fractory indolent B-cell non-Hodgkin's lymphoma (NHL). Methods:A total of 25 patients with rituximab-refractory NHL received bendamustine hydrochloride 120 mg/m2 intravenously on days 1 and 2 of the 21-day cycle. The short-term response, progression free survival, and toxicities were evaluated. Results:The total number of chemotherapy of the 25 patients was 122 cycles, and the median number was 5 cycles. All patients could be evaluated for efficacy. Among the patients, 6 had complete remission, 13 had partial remis-sion, 3 had stable disease, and 3 had progression disease. The overall response rate and clinical benefit rate were 76%and 88%, respec-tively. Until the deadline, 13 patients had progression disease. The median duration of response was 8 months, and the median progres-sion-free survival (PFS) was 9.3 months. Subgroup analysis showed that PFS is significantly related to bone marrow involvement and serum LDH level (P<0.05). The main adverse effects were myelosuppression, gastrointestinal reactions, and infection. Rash was found in 2 patients, and 1 case of gastric cancer was discovered after 5 cycles of treatment. Conclusion:Bendamustine hydrochloride was ef-fective and tolerable in patients with rituximab-refractory indolent B-cell NHL.

Clinical progress of bendamustine in the treatment of lymphoma and leukemia / 白血病·淋巴瘤

Bendamustine is a kind of nitrogen mustard derivatives consisting of a 2-chloroethylamine alkylating group and a benzimidazole ring.This special structure grants its anti-cancer mechanism different from other common alkylating agents with double function.Since approved,bendanustine has been widely used to treat henatologic malignancies and solid tumors such as breast cancer.In 2008,the FDA approved bendamustine injection for the treatment of chronic lymphocytic leukemia and indolent B cell non-Hodgkin's lymphoma.In recent years,scholars in China and abroad have carried out a series of clinical researches on single bendamustine and bendamsutine combinational chemotherapy,especially in hematologic malignancies,which obtained certain clinical efficacy.In this paper,the pharmacological actions,pharmacokinetics and clinical progress of bendamustine in lymphoma and leukemia are reviewed.

Derivative Spectrophotometric Methods for the Determination of Bendamustine Hydrochloride.

Bendamustine hydrochloride is used to treat chronic lymphocytic leukemia. It kills the existing cancer cells and limits the growth of new cancer cells. Three simple, rapid and sensitive spectrophotometric methods were developed for the determination of Bendamustine hydrochloride in phosphate buffer (pH 8.0) (Method A) and boric buffer (pH 9.0) (Method B). Method C is a difference spectroscopy technique in which the amplitude was chosen for the analytical calculations. Bendamustine hydrochloride obeys Beer-Lambert’s law over the concentration range 1-40 μg/ml, 0.1-40 μg/ml and 5- 40 μg/ml with regression equations y = 0.003x + 0.001(r² = 0.998) y = 0.0027x + 0.0005 (r² = 0.999), and y = 0.0034x + 0.006 (r² = 0.994) for Method A, B and C respectively. The methods were validated as per ICH guidelines and can be applied for the determination of Bendamustine hydrochloride in pharmaceutical formulations.