Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals;however,the prognosis remains poor.The BCMA antigen is highly expressed in myeloma cells,thus representing a ta...Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals;however,the prognosis remains poor.The BCMA antigen is highly expressed in myeloma cells,thus representing a target for novel therapies.Several agents that target BCMA through different mechanisms,including bispecific T cell engagers drug conjugated to antibody and CAR-T cells,are now available or under development.Immunotherapies targeting BCMA have shown good results in efficacy and safety in multiple myeloma patients previously treated with several lines of therapy.This review will discuss the recent development of anti-BCMA targeted treatments in myeloma,with a special focus on currently available agents.展开更多
Great progress has been made in improving survival in multiple myeloma(MM)patients over the last 30 years.New drugs have been introduced and complete responses are frequently seen.However,the majority of MM patients d...Great progress has been made in improving survival in multiple myeloma(MM)patients over the last 30 years.New drugs have been introduced and complete responses are frequently seen.However,the majority of MM patients do experience a relapse at a variable time after treatment,and ultimately the disease becomes drug-resistant following therapies.Recently,minimal residual disease(MRD)detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response.MRD can be considered as a surrogate for both progression-free and overall survival.In this perspective,the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals.The present review gives an overview of drug resistance in MM,i.e.,mutation ofβ5 subunit of the proteasome;upregulation of pumps of efflux;heat shock protein induction for proteasome inhibitors;downregulation of CRBN expression;deregulation of IRF4 expression;mutation of CRBN,IKZF1,and IKZF3 for immunomodulatory drugs and decreased target expression;complement protein increase;sBCMA increase;and BCMA down expression for monoclonal antibodies.Multicolor flow cytometry,or next-generation flow,and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5.Sustained MRD negativity is related to prolonged survival,and it is evaluated in all recent clinical trials as a surrogate of drug efficacy.展开更多
文摘Recent advances in multiple myeloma therapy have increased the depth of response and ultimately survivals;however,the prognosis remains poor.The BCMA antigen is highly expressed in myeloma cells,thus representing a target for novel therapies.Several agents that target BCMA through different mechanisms,including bispecific T cell engagers drug conjugated to antibody and CAR-T cells,are now available or under development.Immunotherapies targeting BCMA have shown good results in efficacy and safety in multiple myeloma patients previously treated with several lines of therapy.This review will discuss the recent development of anti-BCMA targeted treatments in myeloma,with a special focus on currently available agents.
文摘Great progress has been made in improving survival in multiple myeloma(MM)patients over the last 30 years.New drugs have been introduced and complete responses are frequently seen.However,the majority of MM patients do experience a relapse at a variable time after treatment,and ultimately the disease becomes drug-resistant following therapies.Recently,minimal residual disease(MRD)detection has been introduced in clinical trials utilizing novel therapeutic agents to measure the depth of response.MRD can be considered as a surrogate for both progression-free and overall survival.In this perspective,the persistence of a residual therapy-resistant myeloma plasma cell clone can be associated with inferior survivals.The present review gives an overview of drug resistance in MM,i.e.,mutation ofβ5 subunit of the proteasome;upregulation of pumps of efflux;heat shock protein induction for proteasome inhibitors;downregulation of CRBN expression;deregulation of IRF4 expression;mutation of CRBN,IKZF1,and IKZF3 for immunomodulatory drugs and decreased target expression;complement protein increase;sBCMA increase;and BCMA down expression for monoclonal antibodies.Multicolor flow cytometry,or next-generation flow,and next-generation sequencing are currently the techniques available to measure MRD with sensitivity at 10-5.Sustained MRD negativity is related to prolonged survival,and it is evaluated in all recent clinical trials as a surrogate of drug efficacy.
