Case Study Of The Resistance Of Bortezolm And The Literature Review

[Objective]Based on bortezomib in multiple myeloma treatment primary drug-resistant cases analysis,to study the clinical performance of multiple myeloma?epidemiological trends of drug resistance?Resistance in clinical feature selection and treatment resistance mechanisms,in order to improve the understanding of bortezomib resistant and realize the individualized treatment of multiple myeloma.[Methods]Review 3 cases of multiple myeloma treatment with bortezomib,analyse clinical data,combined with domestic and foreign literature for how to identify drug-resistant bortezomib?the epidemiological status of pathogenesis of primary resistancethe mechanisms of resistance to bortezomib?treatment options of MM.[Results]Case 1:Female,61 years old,with rheumatoid arthritis for 13 years,weak limbs joint pain April.Leukocyte reduction anemia;The protein was elevated(at least 34.6g/L),and the immune-fixed electrophoresis was increased mainly by IgG and the light chain,and the fibrinogen was elevated with the serum beta 2 microglobulin(up to 4.02mg/ml)and fibrinogen increase;creatinine lactate dehydrogenase blood calcium albumin normal,urine protein qualitative negative;The proportion of bone marrow myeloma cells was high,70%,and Fish was not abnormal.No bone damage was observed in the pelvis X of the thoracolumbar vertebra.Clinical diagnosis:multiple myeloma IgG-k? stage(ISS staging).Treatment:after 3 courses of chemotherapy based on borotizonib.assess the effect of treatment of PD,it was unsuccessful,adjustment for 2 CTDA regimen for treatment,after the first course of globulin.IgG and serum free light chain ratio decreased,the index to rise again as the second course,plasma cells,bone marrow ratio of 50%at the same time;Consider disease progression,and once again be the basis of the drug lenalidomide chemotherapy regimens,line a total of three courses of treatment,during the review of globulin and IgG and gradually reduce the serum free light chain ratio,plasma cells,bone marrow proportion fell to 35%,due to the patient's white blood cells and neutropenia,therefore,not the drug lenalidomide chemotherapy.In the 9th course of chemotherapy,VCD was reintroduced,but the ratio of globulin,IgG and blood free light chain was increased again,and there was no response to treatment.10 courses of chemotherapy with MPR,IV degrees of bone marrow suppression after chemotherapy,pulmonary infection,because of intracranial hemorrhage,septic shock,sepsis,acute left heart failure rescue invalid death,overall survival 32 months.Case 2:Women,62-year-old,The whole blood cell was reduced,with epistaxis and gingival bleeding for 2 years.,combine with complete blood decreases,globulin increases(minimum 53.9 g/L),immunoglobulin inspection is given priority to with IgG and kappa light chain predominate rise;Creatinine,lactate dehydrogenase,urine protein qualitative negative;The proportion of bone myeloma cells was 43%.The frontal,occipital,occipital and left mandible can be seen to have bony destruction.Clinical diagnosis:multiple myeloma IgG-? ? stage(ISS staging);Treatment:after 3 courses of VDT,M protein increased>25%;Evaluation of PD.poor treatment response,borotizol resistance;After the adjustment programme,3 courses of VADT solution,2 courses of M2 and 1 course of MP regimen were successively selected,and the post-chemotherapy globulin and IgG were still very high,with high viscosity and hyperviscosity,and had been replaced by plasma for 4 times.Due to the progress of the disease,the development of plasma cell leukaemia,due to cerebral hemorrhage,lung infection rescue ineffective death,total survival period 22 months.Case 3:Female,65-year-old,weak,poor appetite,cough with epistaxis six mounth,at the same time with moderate anemia,creatinine(minimum tendency for 162.5/l),uric acid,hypercalcemia,?-2 microglobulin increased,bone wear:myeloma proportion is as high as 70%,Bone marrow biopsy and immunohistochemical:CD138(+),Ki-67(about 10%),+ CD3 8 +(part),MUM-1 +(part),Lambda(+)oven,Kappa(+),in line with the plasma cell tumors;immune fixed electrophoretic kappa free light chain type predominate,abnormal karyotype not seen;Flow cytology showed that plasma cells accounted for about 51.5%of total nuclear cells,and immunophenotypes were CD38-++,CD138+,CD19-,CD56+,CD117+,CD200-,intracellular immunoglobulin Kappa light chain restricted expression,for monoclonal plasma cells.Multiple bone destruction throughout the body;Chest PET/CT and CT showed lung cancer in the upper lobe of the right lung,lung puncture biopsy under CT:pasted/attached wall type adenocarcinoma,peripheral blood EGFR did not detect tumor cells;Acid-resistant bacillus and sputum culture:undetected acid-resistant bacillus.Clinical diagnosis:1.Multiple myeloma K light chain phase I(ISS staging);2.Lung adenocarcinoma.Treatment:after 3 courses of VDT,1 course of VCDT,plasma exchange;In addition,there was a new bone destruction in the patient,and there was a new bone destruction in the patients.There was a drug resistance of bortezolamide,and the death of multiple organ failure resulted in a total survival period of 6 months.[Conclusions]In the above 3 cases,the patients were treated with the combination of borotizolm and the normal treatment of 3 courses,through the amount of immunoglobulin;The proportion of plasma cells in bone marrow cells;Blood beta 2 microglobulin;The comprehensive assessment of patients with clinical symptoms of boron for m clinical curative effect,1 patients after 3 courses of treatment and serum immunoglobulin IgG kappa light chain is higher to begin with,predominate plasma cells in bone marrow decline is not obvious,limbs joint pain relief is not obvious,and new bone destruction;After 3 courses of treatment,serum immunoglobulin IgG and serum beta 2 microglobulin were increased,and the decrease of the light chain was not obvious.3 patients in the treatment of slurry after 3 course of bone marrow cells was up 70%,beta 2 micro serum globulin increased to 61.2 mg/1,and new bone destruction of boron was observed in all 3 patients with m poor response to treatment for existence for boron with m primary drug resistanceo Multiple myeloma is a group of heterogeneous disease,clinical manifestations of complex,in the clinical treatment,It is recommended that the chemotherapy regimen of bortezomib is a first-line treatment,If a regular 2-cycle treatment is evaluated for poor efficacy or progression of the disease,we should be taken seriously,consider the possibility of borotizomib resistance,adjust treatment options if necessary,to reduce tumor load and improve the quality of life and prolonged survival time.The treatment of borotizomib-resistance may be based on molecular and genetic selection,including lenalidomide or the second protease inhibitor or Daratumumab,If the disease is not controlled,try cell therapy.The above 3 patients showed resistance to drug change,but they still did not have good efficacy.Due to the small number of cases in this study,we need to expand the sample size,summarize the clinical features of borotizol-resistant patients,assist the diagnosis of MM and develop individualized treatment plan.