OBJECTIVE: To evaluate the therapeutic effect and adverse reactions of the maintenance therapies with Thalidomine or Bortezomib in the patients with newly diagnosed multiple myeloma (MM), so as to provide a reference for clinical treatment. METHODS: A retrospective analysis was conducted to compare the progression-free survival (PFS), overall survival (OS) and adverse reaction rate of 23 MM patients received the maintenance therapies of Bortezomib and of 68 MM patients received maintenance therapy of Thalidomine. RESULTS: The maintenance therapy with Bortezomib could extend the PFS of MM patients as compared with Thalidomine (PFS rate of patients on the maintenance therapy of Bortezomib in 12th, and 24th month was 100%, 88.89%, and that of Thalidomine-treated group was 72.31%, 47.54%). What's more, some specific patients could get better 2-year PFS rate in Bortezomib group than that in Thalidomine group, such as older than 65 years old, after autologous hematopoietic stem cell transplantation(ASCT), having genetic changes, extramedullary lesions, poor renal function, low serum free light chain ratio, high β2-MG, anemia, high LDH, VGPR of induction and consolidation therapy. The OS rate of Bortezomib on 18th, 24th and 30th month was 100%, 88.89%, 80% verus 91.52%,83.63%,72.90% of the group with thalidemide at the same time. As for 2-year OS rate, the Bortezomib group was higher than Thalidomine without statistical differences. However, the patients such as older than 65 years old, poor renal function and with extramedullary lesions, would also get higher 2-year OS rate from Bortezomi. Bortezomib and thalidomide could cause bone marrow suppression, peripheral neuritis and other adverse reactions. CONCLUSION The efficacy of maintenance therapy with Bortezomib is superior to thalidomide. As a conclusion, bortezomib is a better option for maintenance therapy of MM patient.
Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; Bortezomib ; administration & dosage ; Disease-Free Survival ; Humans ; Multiple Myeloma ; drug therapy ; Pyrazines ; Retrospective Studies ; Thalidomide ; administration & dosage ; Transplantation, Autologous ; Treatment Outcome

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.
Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Bacterial Infections/*complications/microbiology ; Bortezomib/*administration & dosage ; Female ; Gram-Negative Bacteria/isolation & purification ; Gram-Positive Bacteria/isolation & purification ; Humans ; Lymphocyte Count ; Lymphopenia/*therapy ; Male ; Middle Aged ; Multiple Myeloma/complications/*drug therapy/mortality ; Multivariate Analysis ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Stem Cell Transplantation ; Survival Rate ; Transplantation, Homologous

OBJECTIVETo investigate the clinical efficacy and safety of conventional dose and reduction dose of bortezomib in combination with bisphosphonates for treating patients with multiple myeloma ostespathy.

METHODSA total of 150 patients with multiple myeloma ostespathy were chosen in the period from March 2011 to July 2015 and randomly were divided into 2 groups: A group (75 cases) and B group (75 cases). The patients in A and B groups were treated with conventional dose of bortezomib and reduction dose of bortezomib on the basis of bisphosphonates respectively and the clinical efficacy, the improvement rate of life quality, NRS score, levels of IL-6 and CRP before and after treatment, and the adverse effects of 2 groups were compared.

RESULTSThere was no significant difference in the clinical efficacy between 2 groups (P<0.05). The improvement rate of patients life quality in B group was significantly better than that in A group (P>0.05). There was no significant difference in the NRS score, levels of IL-6 and CRP after treatment between 2 groups (P>0.05). There was no significant difference in the incidence of neutrophil reduction and thrombocytopenia between 2 groups (P<0.05). The incidence of BiPN, nausea and vomiting, herpes zoster and fatigue of B group was significantly lower than that in A group (P<0.05).

CONCLUSIONConventional dose and reduction dose of bortezomib in combination with bisphosphonates for treating patients with multiple myeloma ostespathy possess the same effects, including pain relief and disease progression control; but the reduction dose of bortezomib application can efficiently improve the life quality of patients and reduce the risk of adverse reactions.

Antineoplastic Agents ; administration & dosage ; therapeutic use ; Bortezomib ; administration & dosage ; chemistry ; therapeutic use ; C-Reactive Protein ; analysis ; Diphosphonates ; administration & dosage ; therapeutic use ; Disease Progression ; Humans ; Interleukin-6 ; analysis ; Multiple Myeloma ; drug therapy

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
Aged ; Aminopterin/adverse effects/*analogs & derivatives/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bortezomib/adverse effects/*therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Lymphoma, T-Cell, Peripheral/diagnostic imaging/*drug therapy/pathology ; Male ; Neoplasm Recurrence, Local ; Neutropenia/etiology ; Positron Emission Tomography Computed Tomography

OBJECTIVETo investigate the effect of CAL-101, a selective inhibitor of PI3Kδ, in combination with bortezomib on the proliferation and apoptosis in human mantle cell lymphoma cell lines Z138, HBL-2 and Jeko-1 in vitro, to explore its mechanisms and provide the foundation for effective treatment strategies against mantle cell lymphoma.

METHODSMTT assay was applied to detect the inhibitory effects of CAL-101 and bortezomib either alone or combined on Z138, HBL-2 and Jeko-1 cells. Calcusyn software was used to analyze the synergistic cytotoxicity. Western blot was used to detect the expression of PI3K-p110σ and p-Akt, Akt, p-ERK and ERK proteins after the cells were exposed to different concentrations of CAL-101. Flow cytometry was employed to assess the apoptosis rate. NF-κB kit was used to determine the changes of location of NF-κB P65, and Western blot was applied to detect the level of caswpase-3 and the phosphorylation of Akt in different groups.

RESULTSCAL-101 and BTZ inhibited the proliferation of Z138, HBL-2 and Jeko-1 cells in a dose- and time-dependent manner. CAL-101/BTZ combination induced significantly synergistic cytotoxicity in the MCL cells. The results of Western blot assay showed that CAL-101 significantly blocked the phosphorylation of Akt and ERK in the MCL cell lines. In addition, CAL-101 combined with BTZ induced pronounced apoptosis (P < 0.01). For example, after the Z138 cells exposed to the drugs for 48 h, the apoptosis rates of the control, CAL-101, BTZ and CAL-101 + BTZ groups were: (2.6 ± 1.8)%, (40.0 ± 3.0)%, (34.0 ± 1.0)%, and (67.4 ± 1.0)%, respectively; and when drug treatment was given to HBL-2 cells over 96 h, the apoptosis rates of these four cell groups were (7.4 ± 0.6)%, (30.7 ± 5.7)%, (12.0 ± 1.0)%, and (85.0 ± 4.0)%, respectively. The combination therapy contributed to the enhanced inactivity of nuclear factor-κB (NF-κB) and Akt inactivation in the MCL cell lines (P < 0.05), however, the casepase-3 activity was up-regulated.

CONCLUSIONSThe combination of CAL-101 and bortezomib is muchmore effective in inhibiting proliferation and promoting apoptosis of mantle cell lymphoma cell lines (Z138, HBL-2 and Jeko-1), which may be mediated through inhibiting PI3K/Akt signaling pathway and the transcription of NF-κB.

Antineoplastic Agents ; pharmacology ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Apoptosis ; drug effects ; Blotting, Western ; Boronic Acids ; Bortezomib ; pharmacology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Class Ia Phosphatidylinositol 3-Kinase ; antagonists & inhibitors ; Dose-Response Relationship, Drug ; Drug Synergism ; Formazans ; Humans ; Lymphoma, Mantle-Cell ; drug therapy ; pathology ; MAP Kinase Signaling System ; drug effects ; NF-kappa B ; metabolism ; Neoplasm Proteins ; metabolism ; Phosphatidylinositol 3-Kinases ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Purines ; administration & dosage ; pharmacology ; Pyrazines ; Quinazolinones ; administration & dosage ; pharmacology ; Signal Transduction ; Software ; Tetrazolium Salts

PURPOSE: Recently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR. MATERIALS AND METHODS: Eleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11. RESULTS: Bortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91+/-22.15 mL/min/1.73 m2) versus eGFR at time of AMR diagnosis (17.00+/-9.25 mL/min/1.73 m2; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function. CONCLUSION: Anti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.
Adolescent ; Adult ; Antibodies, Monoclonal/therapeutic use ; Antineoplastic Agents/*therapeutic use ; Boronic Acids/therapeutic use ; Bortezomib/*therapeutic use ; Female ; Graft Rejection/*drug therapy/*prevention & control ; Humans ; Immunoglobulins, Intravenous/therapeutic use ; Immunologic Factors/therapeutic use ; Isoantibodies ; Kidney Failure, Chronic/*surgery ; *Kidney Transplantation ; Male ; Middle Aged ; Plasmapheresis ; Pyrazines/administration & dosage ; Transplantation, Homologous

OBJECTIVETo evaluate the efficacy and safety of bortezomib-based chemotherapy for 80 patients with multiple myeloma (MM).

METHODSA total of 80 cases with a median age of 57 (range: 25-78) years were enrolled in the study. Bortezomib-based regimens included VD (bortezomib and dexamethasone) and PAD (bortezomib, doxorubicin and dexamethasone). 16 of the 80 patients received autologous or allo-hematopoietic stem cell transplantation (HSCT).

RESULTSThe overall response (OR) rate was 80%, including a complete response (CR) of 46.3%. After a median follow-up of 25 months, the 1-year and 2-year overall survival (OS) was 81.4% and 72.9%, and the 2-year progression-free survival (PFS) was 76% and 62.5%, respectively. The 2-year OS and PFS were 100% and 73.9 % in patients with HSCT, while both were 66% (P=0.029) and 58.7% (P=0.447) in patients without HSCT. In univariate analysis, Durie-Salmon group, ISS stage, CR and very good partial response (VGPR), and HSCT were prognostic factors for OS. Gender and extramedullary plasmacytomas were important prognostic factors for PFS. Multivariate analysis by Cox regression revealed that CR and VGPR, Durie-Salmon group A, and HSCT were prognostic factors for better OS; while male and patients without extramedullary plasmacytomas were prognostic factors for longer PFS.

CONCLUSIONMM patients could benefit from bortezomib-based chemotherapy with satisfactory efficacy and safety. HSCT could improve the OS for young MM patients.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; drug therapy ; therapy ; Prognosis ; Pyrazines ; administration & dosage ; Treatment Outcome

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Humans ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage

This study was aimed to evaluate the clinical characteristics of immunoglobin D multiple myeloma (IgD MM) and its curative efficacy. The clinical data of 15 cases of newly diagnosed IgD MM from April 1993 to June 2013 were analyzed retrospectively. Among 15 cases received induction treatment, the traditional chemotherapy was carried out in 9 cases, bortezomib-based therapy was performed in 6 cases. The diagnostic criteria and disease response criteria of MM were based on International Myeloma Working Group (IMWG) criteria,survival time was analyzed by using Kaplan-Meier method, the median age of patients was 57 years (range 40-72), the ratio of male to female was 2:1, the MM patients in Durie-Salmon stage III accounted for 100% (15/15) , the MM patients with λ light chain accounts for 80% (12/15) , with bone lesion 86.7% (13/15), with pleural effusion 26.7% (4/15) , with renal impairment (RI) 86.7% (13/15) ,with anemia 93.3% (14/15) , with serum album<35 g/L 26.7% (4/15). The median creatinine clearance rate (Ccr) of patients was 23.1 (6-44) ml/min, and median hemoglobin level was 82 (43-131) g/L. The results showed that in followed-up 11 cases, 8 cases died, 3 cases survived; the average duration of follow-up for these cases was 20 (0.5-138) months, the median progression-free survival time (PFS) was 7 (95%CI4.6-9.4) months, and the median overall survival (OS) time was 15 (95%CI6.6-27.4 ) months. Compared traditional chemotherapy with bortezomib regimen therapy,median OS time was 17 (95%CI6.1-28.0) months vs 15 (95%CI 0.0-33.3) months (P = 0.90) . Assessable curative effect of 14 cases was as follows: CR 33.3% (5/15); VGPR 13.3% (2/15); PR 20% (3/15); SD 20% (3/15); PD 6.7% (1/15). It is concluded that IgD MM is a rare type of MM and has a poor prognosis. Bortezomib may be beneficial for some patients with extramedullary infiltration. Autologous hematopoietic stem cell transplantation may improve survival time.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Disease-Free Survival ; Female ; Humans ; Immunoglobulins ; immunology ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; immunology ; Pyrazines ; administration & dosage ; Retrospective Studies

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; Bortezomib ; Humans ; Multiple Myeloma ; diagnosis ; drug therapy ; Pyrazines ; administration & dosage