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 ur...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.展开更多
Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of pati...Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of patients,intrinsic or acquired drug resistance occurs.Constitutional genetics may help to predict R-CHOP resistance.This study aimed to validate previously identified single nucleotide polymorphisms(SNPs)in the literature as potential predictors of R-CHOP resistance in DLBCL patients,SNPs.Methods:Twenty SNPs,involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes,were investigated in 185 stage Ⅰ-Ⅳ DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP.Results:Correlations between rs2010963(VEGFA gene)and sex(P=0.046),and rs1625895(TP53 gene)and stage(P=0.003)were shown.After multivariate analyses,a concordant effect(i.e.,increased risk of disease progression and death)was observed for rs1883112(NCF4 gene)and rs1800871(IL10 gene).When patients were grouped according to the revised International Prognostic Index(R-IPI),both these SNPs further discriminated progression-free survival(PFS)and overall survival(OS)of the R-IPI-1-2 subgroup.Overall,patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients.Conclusions:Two out of the 20 study SNPs were validated.Thus,these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients.These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.展开更多
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.
基金funded by the Associazione Giacomo Onlus 2012-2020(Castiglioncello,Italy)(to Mini E)Fondazione Cassa di Risparmio di Firenze-ref.no.2013.0842 and ref.no.2014.0969(Firenze,Italy)(to Nobili S).
文摘Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of patients,intrinsic or acquired drug resistance occurs.Constitutional genetics may help to predict R-CHOP resistance.This study aimed to validate previously identified single nucleotide polymorphisms(SNPs)in the literature as potential predictors of R-CHOP resistance in DLBCL patients,SNPs.Methods:Twenty SNPs,involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes,were investigated in 185 stage Ⅰ-Ⅳ DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP.Results:Correlations between rs2010963(VEGFA gene)and sex(P=0.046),and rs1625895(TP53 gene)and stage(P=0.003)were shown.After multivariate analyses,a concordant effect(i.e.,increased risk of disease progression and death)was observed for rs1883112(NCF4 gene)and rs1800871(IL10 gene).When patients were grouped according to the revised International Prognostic Index(R-IPI),both these SNPs further discriminated progression-free survival(PFS)and overall survival(OS)of the R-IPI-1-2 subgroup.Overall,patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients.Conclusions:Two out of the 20 study SNPs were validated.Thus,these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients.These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.
