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| 1 | Drug resistance and minimal residual disease in multiple myeloma显示文摘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. | Alessandro Gozzetti Sara Ciofini Anna Sicuranza Paola Pacelli Donatella Raspadori Emanuele Cencini Dania Tocci Monica Bocchia | 2022 | Cancer Drug Resistance2022，5，1： | 1 |
| 2 | Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas显示文摘T-cell lymphomas(TCLs)represent a group of lymphoid neoplasms characterized by an aggressive clinical course,even after an anthracycline-containing regimen.Novel agents for patients with relapsed/refractory TCL are urgently needed.Lenalidomide is an oral drug with immunomodulatory,antiangiogenic and direct antineoplastic effects.These peculiar mechanisms of action make TCL an attractive target for lenalidomide.We have identified five clinical trials in which lenalidomide monotherapy was investigated to treat TCL,including cutaneous TCL(CTCL)and adult T-cell lymphoma/leukemia(ATLL).In the ATLL-002 study,the overall response rate(ORR)was 42%and median progression-free survival(PFS)and overall survival were 3.8 mo and 20.3 mo,respectively.In a phase II trial for CTCL,ORR was 28%and median PFS and overall survival were 8 mo and 43 mo,respectively.For nodal peripheral TCL,ORR was between 10%and 43%in three clinical trials,with a median PFS of about 4 mo,even if some patients had a durable response.Overall toxicity is manageable and grade 3-4 events are mainly hematological and reversible.Combination strategies did not improve PFS.In conclusion,lenalidomide could represent a suitable treatment option for relapsed/refractory TCL,especially for neoplasms with a T-follicular helper origin,such as angioimmunoblastic TCL. | Emanuele Cencini Alberto Fabbri Bianca Mecacci Monica Bocchia | 2021 | World Journal of Clinical Oncology2021，12，10： | 0 |
| 3 | Anti-BCMA novel therapies for multiple myeloma显示文摘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. | Vincenzo Sammartano Marta Franceschini Sara Fredducci Federico Caroni Sara Ciofini Paola Pacelli Monica Bocchia Alessandro Gozzetti | 2023 | Cancer Drug Resistance2023，6，1： | 0 |
| 4 | Liquid biopsy and blood-based minimal residual disease evaluation in multiple myeloma显示文摘Novel drug availability has increased the depth of response and revolutionised the outcomes of multiple myeloma patients.Minimal residual disease evaluation is a surrogate for progression-free survival and overall survival and has become widely used not-only in clinical trials but also in daily patient management.Bone marrow aspiration is the gold standard for response evaluation,but due to the patchy nature of myeloma,false negatives are possible.Liquid biopsy and blood-based minimal residual disease evaluation consider circulating plasma cells,mass spectrometry or circulating tumour DNA.This approach is less invasive,can provide a more comprehensive picture of the disease and could become the future of response evaluation in multiple myeloma patients. | ALESSANDRO GOZZETTI MONICA BOCCHIA | 2023 | Oncology Research2023，31，3： | 0 |
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