BACKGROUND: Multiple myeloma is a malignant proliferation of plasma cells that accumulate in the bone marrow and results in several organ dysfunctions that are debilitating and fatal. For the past 20 years, advances in the understanding of genetic abnormalities, interactions in the bone marrow microenvironment, developments in the diagnosis and staging in myeloma and introduction and incorporation of novel agents early in the disease course have been pivotal in the clinical treatment and management of patients with multiple myeloma. However, the burden associated with the disease, including treatment costs, is significant for Filipino patients as it is still incurable. In the Philippines, the introduction of bortezomib in the market in the last decade have brought hope to many patients by expanding the availability of treatment options, improving quality of life and extending survival. METHODS: This paper documents the proceedings of a forum on multiple myeloma conducted last March 2018 at Makati City. The purpose of the forum was to discuss the major clinical presentations of the disease as well as treatment and management of selected patients. Speakers were hematology and medical oncology experts in the Philippines. RESULTS: Five cases of multiple myeloma with different clinical presentations and management were discussed: (1) renal insufficiency, (2) easy fatigability, (3) bone pain, (4) autologous stem cell/bone marrow transplantation and (5) coagulopathy. Short videos of selected patients (or their family members) after each presentation was showed, describing their treatment journey with myeloma. Other patients with multiple myeloma who were treated with bortezomib were present in the forum and briefly shared their experiences. CONCLUSION As multiple myeloma is a highly heterogeneous molecular disease, approaches and provision of care will need to be individualized for each patient. Because of its impressive performance, bortezomib is likely to continue being an important part of the clinical treatment and management of Filipino patients with myeloma.
Bortezomib

No abstract available.
Multiple Myeloma* ; Bortezomib

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) also known as Crow-Fukase syndrome or Takatsuki syndrome is a rare and disabling paraneoplastic syndrome that frequently occurs in the fifth or sixth decade of life without a known standard first-line therapy. A 34-year-old Filipino male nurse, who presented with gradually progressive distal lower extremity weakness and sharp shooting pain in bilateral legs accompanied by mild joint effusion on the left knee, hypertrichosis, bilateral conjunctival injection, and gynecomastia underwent extensive workup and was diagnosed with POEMS syndrome. Complete blood count revealed erythrocytosis and thrombocytosis with elevated serum VEGF (vascular endothelial growth factor) and elevated monoclonal serum free lambda light chains. The electrophysiologic studies revealed chronic demyelinating sensorimotor polyneuropathy while bone marrow core biopsy and bone marrow aspirate smear immunohistochemical staining showed it to be positive for lambda and CD138. He had an initial unsuccessful treatment course with melphalan and prednisone. Hence, bortezomib and dexamethasone were given which gave significant improvement in symptoms from the overall neuropathy limitation score of 5 to 1.

OBJECTIVETo investigate if Ad-NK4 can enhance the chemosensitivity of human multiple myeloma RPMI 8226 cells to bortezomib(BOR).

METHODSThe cell-matrix adhesion test and PRMI 8226 cell-ECV 304 cell adhesion test were used to analyze the effect of Ad-NK4 on adhesion of RPMI 8226 cells; Western blot was used to detect the expression changes of adhesion and invasion-associated proteins MMP2, MMP3, MMP7 and VEGF; MTT assay was used to detect the effect of Ad-NK4 on proliferation of RPMI 8226 cells; the flow cytometry with PI staining was used to detect the effect of Ad-NK4 on cell apoptosis; the expression of cleaved caspase-3, BAX and BCL-2 was assayed by Western blot.

RESULTSThese 2 adhesion assays indicated that Ad-NK4 significantly inhibited the adhesion of human multiple myeloma RPMI 8226 cells. In addition, Erk and JAK/STAT pathway may be involved in the process. The expression level of MMP-2, MMP-3 and VEGF were decreased in Ad-NK4 group, compared with untreated or Ad-GFP group (P<0.05). However, the expression of MMP-7 protein in Ad-NK4 group was not significantly different from untreated or Ad-GFP group (P>0.05). The inhibitory rates of the proliferation in cells treatedly Ad-NK4 combined with BOR was significantly higher than that with BOR or Ad-NK4 alone. Similarly, Western blot indicated that the level of cleaved caspase-3 and BAX in cells treated with Ad-NK4 combined with BOR was significantly higher than BOR or Ad-NK4 alone, but BCL-2 protein expression was significantly lower. Meanwhile, the ratio of BAX/BCL-2 was increased.

CONCLUSIONAd-NK4 can enhance the chemosensitivity of human multiple myeloma RPMI 8226 cells to BOR,which is associated with increasing of both BAX/BCL-2 ratio and Caspase-3 activation.

Bortezomib is a proteasome inhibitor used for the treatment of patients with multiple myeloma. Recently, several case reports about acute pancreatitis caused by Bortezomib were published in the international literature. But Bortezomib induced pancreatitis case was not reported in Korea. Herein, we report a case of acute pancreatitis caused by Bortezomib therapy in a 76-year-old female with multiple myeloma. On three months after the first administration of Bortezomib, the patient visited the hospital with symptoms of acute pancreatitis. The common etiological factors for acute pancreatitis were all excluded. Then the patient was diagnosed as Bortezomib-induced pancreatitis. After cessation of Bortezomib, she showed clinical and laboratory improvement.
Aged ; Female ; Humans ; Korea ; Multiple Myeloma* ; Pancreatitis* ; Proteasome Inhibitors ; Bortezomib

Bortezomib ; therapeutic use ; Drug Combinations ; Humans ; Multiple Myeloma ; drug therapy

Boronic Acids ; Bortezomib ; Humans ; Liver Diseases ; Proteasome Inhibitors ; Pyrazines

Bortezomib ; Dexamethasone ; Drug Combinations ; Humans ; Multiple Myeloma ; Rhabdomyolysis

OBJECTIVE: To investigate the role of exosome in mediating bortezomib (Btz) resistance in multiple myeloma cells and explore the underlying mechanisms. METHODS: Peripheral blood samples were collected from 15 patients with multiple myeloma with Btz tolerance, and serum exosomes were isolated by ultracentrifugation and identified with electron microscopy, NTA and Western blotting. cultured multiple myeloma cells were treated with gradient concentrations of Btz to determine the optimal drug concentration for subsequent experiment. The cells were pretreated with different concentrations of exosomes, and their sensitivity to BTZ was assessed using MTS assay. We searched the exosome database Exocarta and used STRING to generate the network map and the protein interaction graph. RESULTS: The diameters of the vesicles isolated from the peripheral blood of the patients were mostly below 200 nm with a mean particle size of 153 nm and a mode of 140.1 nm. The results of Western blotting showed that the isolated exosomes expressed the marker proteins CD63, Tsg101 and Alix. In cultured multiple myeloma cells, pretreatment with exosomes resulted in a decreased sensitivity of the cells to bortezomib, and longer treatment durations and higher exosome concentrations consistently enhanced the resistance of the cells to the same Btz concentration. Analysis of the Exocarta database identified human serum exosomal proteins ABCB1, ABCB4, PDCD6IP, and EGFR, among which EGFR served as a network node. CONCLUSIONS Exosome within a specific concentration range may serve as a signal carrier to mediate the resistance of multiple myeloma cells to Btz. EGFR likely plays a key role to promote exosome-mediated Btz resistance in myeloma cells.
Bortezomib ; Drug Resistance, Neoplasm ; Exosomes ; Humans ; Multiple Myeloma ; Ultracentrifugation

OBJECTIVE: To compare the efficacy and safety of different chemotherapy regimens in elderly multiple myeloma (MM) patients with different Frailty scores. METHODS: The clinical data of elderly patients with MM were retrospectively analyzed, including age, treatment regimen, efficacy, adverse reactions, and the Frailty score included in the activity of daily living score, the instrumental activity of daily living scale and the Charlson comorbidity index. The patients were divided into fit group, mediate fit group and frail group according to the scoring standard. The treatment efficiency and adverse reaction rates of elderly MM with different physical conditions treated by different chemotherapy regimens were analyzed. RESULTS: Among the 70 patients, the effective rates of the patients in fit group, the mediate fit group, and the frail group were 79.5%, 81%, and 40%, and the effective rates of the fit patients in double and triple groups were 54.5% and 89.3%, 70% and 90.9% for mediate fit patients, 42.9% and 33.3% for frail patients, the triple regimen in fit patients showed obvious advantages, and the difference showed statistically significant (P<0.05), while the efficacy for mediate patients and frail patients showed no significant difference. During the induction of bortezomib, the incidence of adverse reactions for the patients in the triple group (78.6%) was higher than 67.9% in the double group, and the difference showed no statistically significant (P>0.05).There was no significant difference in the 1-year overall survival rate of the patients and with molecular genetic abnormalities among each groups. CONCLUSION The therapeutic effect is related to the patient's physical condition. For patients with healthy physique, the triple regimen should be used first. For patients with weak physical constitution, the chemotherapy regimen with low drug toxicity should be selected for safety.
Aged ; Bortezomib ; Frailty ; Humans ; Multiple Myeloma/drug therapy* ; Retrospective Studies