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

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

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

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

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

Bortezomib is an inhibitor of 26S proteasome, which is an effective treatment for multiple myeloma. The common adverse effects of bortezomib are asthenic conditions, gastrointestinal disturbances, and peripheral neuropathy. Here we describe a patient with dyspnea and general weakness because of complete atrioventricular block while receiving bortezomib. We immediately stopped bortezomib, and after inserting a permanent VDD pacemaker, the patients' symptoms disappeared.
Atrioventricular Block/*chemically induced ; Boronic Acids/*adverse effects/*therapeutic use ; Female ; Humans ; Middle Aged ; Multiple Myeloma/*drug therapy ; Pyrazines/*adverse effects/*therapeutic use

Bortezomib is an inhibitor of 26S proteasome, which is an effective treatment for multiple myeloma. The common adverse effects of bortezomib are asthenic conditions, gastrointestinal disturbances, and peripheral neuropathy. Here we describe a patient with dyspnea and general weakness because of complete atrioventricular block while receiving bortezomib. We immediately stopped bortezomib, and after inserting a permanent VDD pacemaker, the patients' symptoms disappeared.
Atrioventricular Block/*chemically induced ; Boronic Acids/*adverse effects/*therapeutic use ; Female ; Humans ; Middle Aged ; Multiple Myeloma/*drug therapy ; Pyrazines/*adverse effects/*therapeutic use

BACKGROUND: Free light chain (FLC) is widely used to evaluate B-cell proliferative diseases. Herein, we estimated the clinical usefulness of serum FLC in multiple myeloma (MM). METHODS: Fifty-one patients were enrolled. We performed FLC analysis, protein electrophoresis (PEP), and immunofixation electrophoresis (IFE). FLC was measured using Toshiba 200 FR Neo with FREELITE(TM), and kappa/lambda (kappa/lambda) ratio was calculated. We compared these parameters in 41 patients with increased FLC before and after bortezomib treatment. Complete response (CR) was defined as the disappearance of monoclonal (M) protein in serum and/or urine as measured by IFE. Partial response (PR) was defined as > or =50% reduction of serum M protein. Early objective response (EOR) included both CR and PR. Minimal response (MR) was defined as 25-49% reduction of M protein and stable disease (SD) as <25% reduction. RESULTS: Forty-one (80.4%) of the 51 patients studied revealed increment of FLC and the five patients with no increment revealed an abnormal kappa/lambda ratio. Especially, all of the light chain myeloma and non-secretory myeloma showed increased FLC concentrations. Among the patients with EOR, 72.4% (21/29) showed a normal or subnormal FLC concentration after the first cycle of treatment. Otherwise, PEP and IFE normalized in 24.1% (7/29) and 24.1% (7/29), respectively. The ratio of decreased FLC after the first cycle of treatment was significantly different between EOR and other response groups (MR, SD) (90.6% vs 51.8%, P=0.011). CONCLUSIONS: FLC was considered as a good diagnostic method in complement with PEP and IFE in MM, especially in light chain myeloma or non-secretory myeloma. Moreover, FLC is a useful monitoring tool because it reflects therapy results more rapidly owing to a short serum half-life.
Adult ; Aged ; Boronic Acids/therapeutic use ; Female ; Humans ; Immunoelectrophoresis ; Immunoglobulin Light Chains/*blood/urine ; Male ; Middle Aged ; Multiple Myeloma/*diagnosis/therapy ; Pyrazines/therapeutic use ; Reagent Kits, Diagnostic