OBJECTIVETo evaluate the efficacy and feasibility of bortezomib plus dexamethasone (BD) in patients with primary systemic (AL) amyloidosis.

METHODSEleven AL amyloidosis patients, including four relapsed or progressed after previous therapies and 7 newly diagnosed were treated with BD. Ten patients had two or more organs involved. Precursor protein analysis showed that 1 was κ light chain, 9 λ light chain; 5 patients with positive immunofixation including 1 IgG κ, 3 IgG λ and 1 IgA λ. BD was administered according to standard two-week schedule.

RESULTSEight patients were evaluable, the median number of treatment cycles was 3 (range 1 - 6). Median follow-up duration was 6 months. At least one affected organ response was observed in six patients and median time to organ response was 2 months. Three patients progressed and two of them died. Toxicities were mainly diarrhea, thrombocytopenia, peripheral neuropathy, fatigue and herpes zoster, and 7 evaluable patients who had toxicities were adjusted dosage and 2 of them interrupted therapy. Epilepsia, paralytic ileus, acute cardiac dysfunction, and postural hypotention were occurred in 3 inevaluble patients.

CONCLUSIONBortezomib plus dexamethasone is effective in AL amyloidosis. Adverse events are common, and in some patients are severe.

Amyloidosis ; drug therapy ; Boronic Acids ; therapeutic use ; Bortezomib ; Dexamethasone ; administration & dosage ; Humans ; Multiple Myeloma ; drug therapy

The proteasome is primarily responsible for intracellular protein degradation. The abnormality of its activity is sign of tumorigenesis. It was confirmed that proteasome inhibitors have activities against a variety of malignancies. Bortezomib, the first proteasome inhibitor, obtained permission of clinical trial and on sale. Multiple myeloma patients treated with bortezomib have gained a high overall response rate and complete remission rate. A lot of studies on effects of proteasome inhibitors on leukemias, including plasma cell leukemia; chronic lymphocytic leukemia, adult T cell lymphoma/leukemia, chronic myeloid leukemia and acute myeloid leukemia, were reviewed in this article.
Animals ; Boronic Acids ; therapeutic use ; Bortezomib ; Humans ; Leukemia ; drug therapy ; enzymology ; Multiple Myeloma ; drug therapy ; Protease Inhibitors ; therapeutic use ; Proteasome Inhibitors ; Pyrazines ; therapeutic use

Boronic Acids ; therapeutic use ; Dexamethasone ; therapeutic use ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Male ; Multiple Myeloma ; drug therapy ; therapy ; Pyrazines ; therapeutic use

OBJECTIVETo review this efficacy and safety of bortezomib, a proteasome inhibitor, in the setting of the sensitized transplant candidate.

DATA SOURCESThe data used in this review were from articles published (PubMed) between 2000 to 2010. Additionally abstracts from medical meetings related to transplant were also used.

STUDY SELECTIONArticles were selected if they were trial results or case studies for the use of bortezomib in the sensitized patient population.

RESULTSThe early data using bortezomib as a part of desensitization regimens has shown success. Although one cycle (4 doses) of bortezomib seems to have affect on many patients, it also seems likely that to provide complete desensitization multiple cycles will be required. Regarding safety, bortezomib has been shown to have minimal side effects. The most common side effects reported are those of thrombocytopenia and anemia. These side effects are dose related and self limiting upon discontinuation of the treatment.

CONCLUSIONSBortezomib with plasmapheresis is a promising new alternative to desensitization protocols that use either high dose intravenous immune globulin (IVIG) or low dose IVIG and plasmapheresis. The efficacy on antibody reduction looks to be batter that that of the IVIG based regimens without significant addition toxicity. The results of ongoing prospective trials are positive and their complete results are greatly anticipated.

Boronic Acids ; therapeutic use ; Bortezomib ; Graft Rejection ; immunology ; prevention & control ; Humans ; Protease Inhibitors ; therapeutic use ; Proteasome Endopeptidase Complex ; metabolism ; Pyrazines ; therapeutic use ; Transplants ; adverse effects

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

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

This study was purpose to explore the therapeutic efficacy and safety of VD regimen and VAD regimen for patients with multiple myeloma. The clinical data of 59 patients with multiple myeloma in our hospital from June 2008 to June 2011 were analyzed retrospectively. The 59 patients with multiple myeloma were divided randomly into VD and VAD groups. The patients in VD group were treated with bortezomib combined dexamethasone. The patients in VAD group were treated with vincristine, doxorubicin and dexamethasone. The efficacy, median survival time, 1-and 2-year survival rate, and toxicity were estimated for the patients in VD group and VAD group. The results showed that the efficacy in the VD group and VAD group was 83.78% and 59.09% respectively. The efficacy in the VD group was significantly higher than that in the VAD group (P < 0.05). The median survival time and 1-and 2-year survival rate in VD group were significantly higher than that in VAD group (P < 0.05). The side effects in VD group mainly were haematologic toxicity, gastrointestinal disorder and peripheral neuropathy. The adverse events were mild and tolerable. The main side effects in the VAD group were haematologic toxicity, infection and hair loss. Most of the infectious in VAD group were at Grade III-IV. It is concluded that VD regimen is an effective and safe therapy regimen for multiple myeloma, and it seems significantly superior to VAD regimen and its side effect can be tolerable for the patients.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Boronic Acids ; administration & dosage ; therapeutic use ; Bortezomib ; Dexamethasone ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; administration & dosage ; therapeutic use ; Vincristine ; therapeutic use

This study was aimed to evaluate the therapeutic efficacy of bortezomib combined with autologous peripheral blood hematopoietic stem cell transplantation (autoPBSCT) for patients with multiple myeloma (MM). 5 patients underwent autologous hematopoietic stem cell transplantation. Bortezomib treatment was supplied for patients before autoPBSCT and in the conditioning of transplantation, it was also used in maintaining treatment. Patients with transplantation adopted bortezomib plus melphalan conditioning regimen. The number of infused MNC and number of CD34(+) cells were 4.06×10(8) (4.09×10(8) - 4.37×10(8))/kg and 3.98×10(6) (2.49×10(6) - 8.2×10(6))/kg respectively. The results showed that hematopoiesis was reconstituted in 5 patients, with a neutrophil cell count more than 0.5×10(9)/L at day 14 (13 - 25 days) after transplantation and platelet count more than 50×10(9)/L at day 28 (21 - 41 days) after transplantation. Transplantation-associated death was not observed. 5 patients were disease-free survival. In conclusion, treatment of bortezomib combined with autologous peripheral hematopoietic stem cell transplantation is an effective method for patients with multiple myeloma. Use of bortezomib after transplantation might still be favourable to MM patients, for survival prolongation and life quality improvement.
Adult ; Boronic Acids ; therapeutic use ; Bortezomib ; Combined Modality Therapy ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; therapy ; Peripheral Blood Stem Cell Transplantation ; Pyrazines ; therapeutic use ; Transplantation Conditioning ; methods

Adult ; Boronic Acids ; therapeutic use ; Bortezomib ; Combined Modality Therapy ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; POEMS Syndrome ; therapy ; Pyrazines ; therapeutic use

OBJECTIVETo evaluate the efficacy and safety of bortezomib retreatment in 76 patients with relapsed/refractory multiple myeloma (MM), who previously responded to bortezomib.

METHODSRetrospective analysis of 76 MM patients, who had achieved at least a partial response (PR) on initial bortezomib therapy in our hospital from May 2006 to August 2011, received bortezomib retreatment when they relapsed or progressed.

RESULTSThe overall response rate (ORR) was 60.5%, among them 6.5% patients achieved CR, 5.8% patients achieved very good partial response (VGPR), 38.2% patients achieved PR. Then we further stratified all patients into 3 groups according to the response of initial bortezomib therapy, including CR group, VGPR group and PR group. After bortezomib retreatment, the ORR of the 3 groups was 84.6%, 73.1% and 43.2%, respectively. According to the response of bortezomib retreatment, the patients were divided into 2 groups: group 1 who at least achieved PR, group 2 who showed no response. The median progression-free survival (PFS) after bortezomib retreatment for group 1 and 2 was 7(1-39) and 5(1-14) months, respectively (P>0.05), while the median overall survival (OS) after bortezomib retreatment was 16(2-64) and 8(1-28) months, respectively (P<0.05). Adverse events (AE) were identified in 88% patients during bortezomib retreatment, including neutropenia, diarrhea and thrombocytopenia, only 9.2%(7 patients) reached Ⅲ-Ⅳ grade of AE. Severe peripheral neuropathy occurred in only one patient.

CONCLUSIONBortezomib retreatment regimen is demonstrated a higher response rate in patients who achieved deeper response in initial treatment, with no more adverse events.

Adult ; Aged ; Boronic Acids ; adverse effects ; therapeutic use ; Bortezomib ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; Pyrazines ; adverse effects ; therapeutic use ; Retrospective Studies ; Treatment Outcome