Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objectiv...Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).展开更多
Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treat...Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treatments for MM are aimed primarily at obtaining minimal residual disease(MRD)negativity and achieving persistent control,both of which are believed to be important strategies to prolong survival and improve prognosis in patients with MM.展开更多
Objective:This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia(CLL)and a 17p deletion(17p-)and identify the predictive factors within this subgroup.Methods:The sample of patien...Objective:This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia(CLL)and a 17p deletion(17p-)and identify the predictive factors within this subgroup.Methods:The sample of patients with CLL were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 11q22,13q14 and 17p13;trisomy of bands 12q13;and translocation involving band 14q32.The data from 456 patients with or without a 17p-were retrospectively collected and analyzed.Results:The overall response rate(ORR)in patients with a 17p-was 56.9%,and patients with a high percentage of 17p-(defined as more than 25%of cells harbouring a 17p-)had a lower ORR.The median overall survival(OS)in patients with a 17p-was 78.0 months,which was significantly shorter than the OS in patients without this genetic abnormality(median 162.0 months,P<0.001).Within the subgroup with a 17p-,the progression-free survival was significantly shorter in patients at Binet stage B-C and patients with elevated lactate dehydrogenase(LDH),B symptoms,unmutated IGHV and a high percentage of 17p-.Conclusions:These results indicated that patients with a 17p-CLL have a variable prognosis that might be predicted using simple clinical and laboratory characteristics.展开更多
Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In ...Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.展开更多
OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal dox...OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.展开更多
Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIP...Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.展开更多
To the Editor:Multiple myeloma(MM)is a plasma cell disorder characterized by heterogeneous features.^([1])Accurate risk stratification could predict diverse prognoses of patients with myeloma and attain risk-adapted t...To the Editor:Multiple myeloma(MM)is a plasma cell disorder characterized by heterogeneous features.^([1])Accurate risk stratification could predict diverse prognoses of patients with myeloma and attain risk-adapted therapy to extend their lifespan.Recently,the European Myeloma Network(EMN)conducted a large retrospective analysis involving more than 7000 patients with myeloma and developed a new risk model defined as the Second Revision of International Staging System(R2-ISS),with excellent risk distribution among patients enrolled in clinical trials.^([2])The R2-ISS stratifications were based on weighted risk scores of different prognostic factors:ISS II 1.0 point,ISS III 1.5 points,del(17p)1.0 point,elevated lactate dehydrogenase(LDH)1.0 point,t(4;14)1.0 point,and 1q21+0.5 points.展开更多
To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in...To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in obtaining tumor metaphase for karyotyping and slow cell proliferation,only very few studies have detected the cytogenetic aberration of LPL/WM.[2,3]In addition,6q deletion is the most common cytogenetic aberration in WM,with an incidence rate of about 50%.[2]Nevertheless,other cytogenetic aberrations remain largely unclear,and the prognostic role of cytogenetic aberrations needs to be further explored.In the present study,we systematically analyzed 305 LPL/WM cases in China,focusing on the characteristics and cytogenetic aberrations in Chinese patients.展开更多
MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the...MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the serum of multiple myeloma(MM)patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis.Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing.Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted.CytoHubba was applied to identify the hub miRNAs and core target genes.The LASSO Cox regression model was used to develop the prognostic model,and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients.The top six hub differentially expressed serum exo-miRNAs were identified.513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset.Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing,cellular response to stress,and deubiquitination.13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients,which is associated with the immune microenvironment of MM patients.Our study comprehensively investigated the exo-miRNA profiles in MM patients.A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.展开更多
基金supported by grants from CAMS Innovation Fund for Medical Sciences(CIFMSGrant No.2022-I2M-1-022)。
文摘Objective:Evidence on the prognostic value of autologous stem cell transplantation(ASCT)and minimal residual disease(MRD)dynamics of patients with newly diagnosed multiple myeloma(NDMM)in China is limited.Our objective in the current study was to understand the current care paradigm and outcomes of these patients.Methods:This longitudinal cohort study used historical data from three top-tier hematologic disease care hospitals that contributed to the National Longitudinal Cohort of Hematological Diseases-Multiple Myeloma.Treatment regimens[proteasome inhibitor(PI)-,immunomodulatory drug(IMiD)-,PI+IMiD-based,and conventional],post-induction response,ASCT and MRD status,and survival outcomes[progression-free survival(PFS)and overall survival(OS)]were evaluated.Results:In total,454 patients with NDMM were included(median age,57 years;59.0%males)with a median follow-up of 58.7 months.The overall response rate was 91.0%,83.9%,90.6%,and 60.9%for PI-,IMiD-,PI+IMiD-based,and conventional regimens,respectively.Patients with ASCT during first-line therapy(26.2%)had a longer PFS and OS than patients who did not receive ASCT[median PFS,42.9 vs.21.2 months,P<0.001;median OS,not reached(NR)vs.65.8 months,P<0.001].The median OS was NR,71.5,and 56.6 months among patients with sustained MRD negativity,loss of MRD negativity,and persistent MRD,respectively(P<0.001).Multivariate analysis revealed that the lactic dehydrogenase level,International Staging System stage,extra-medullary disease,and upfront ASCT were independent factors in predicting OS among NDMM patients.Conclusions:Our study showed that novel agent-based regimens,first-line ASCT,and sustained MRD negativity were associated with a superior outcome for patients with NDMM in China(Identifier:NCT04645199).
基金supported by the International Cooperation Projects of National Natural Science Foundation of China(Grant No.81920108006,to L.Qiu)CAMS Innovation Fund for Medical Sciences(CIFMS)(Grant No.2022-I2M-1-022,to L.Qiu)+1 种基金the National Natural Science Foundation of China(Grant No.81630007,to L.QiuGrant Nos.82270218,81670202,to G.An)。
文摘Introduction Multiple myeloma(MM),characterized by the proliferation of monoclonal plasma cells in the bone marrow,has the second highest incidence among hematologic malignancies1.Because of its incurable nature,treatments for MM are aimed primarily at obtaining minimal residual disease(MRD)negativity and achieving persistent control,both of which are believed to be important strategies to prolong survival and improve prognosis in patients with MM.
基金supported by grants from the National Nature Science Foundation of China (No. 81200395, 81370632)the National Science and Technology supporting Program (No. 2014BAI09B12)+1 种基金the Fundamental Application and Advanced Technology Research Program of Tianjin (No. 15JCYBJC27900)the National Public Health Grand Research Foundation (No. 201202017)
文摘Objective:This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia(CLL)and a 17p deletion(17p-)and identify the predictive factors within this subgroup.Methods:The sample of patients with CLL were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 11q22,13q14 and 17p13;trisomy of bands 12q13;and translocation involving band 14q32.The data from 456 patients with or without a 17p-were retrospectively collected and analyzed.Results:The overall response rate(ORR)in patients with a 17p-was 56.9%,and patients with a high percentage of 17p-(defined as more than 25%of cells harbouring a 17p-)had a lower ORR.The median overall survival(OS)in patients with a 17p-was 78.0 months,which was significantly shorter than the OS in patients without this genetic abnormality(median 162.0 months,P<0.001).Within the subgroup with a 17p-,the progression-free survival was significantly shorter in patients at Binet stage B-C and patients with elevated lactate dehydrogenase(LDH),B symptoms,unmutated IGHV and a high percentage of 17p-.Conclusions:These results indicated that patients with a 17p-CLL have a variable prognosis that might be predicted using simple clinical and laboratory characteristics.
文摘Background: Despite the recent development of new therapies, multiple myeloma(MM) remains an incurable disease. Thus, new, efective treatments are urgently needed, particularly for relapsed or refractory MM(RRMM). In an earlier phase I study, a novel form of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) that is currently in clinical development for the treatment of hematologic malignancies, i.e., circularly permuted TRAIL(CPT), was well tolerated at a dose of 2.5 mg/kg per day and showed promising preliminary activity in patients with RRMM. This phase II, open-label, multicenter study further investigated the eicacy and safety of 2.5-mg/kg per day CPT as single-agent therapy for patients with RRMM.Methods: Patients with RRMM were treated once daily with CPT(2.5 mg/kg, intravenously) for 14 consecutive days for each 21-day cycle. Clinical response and toxicity were assessed after each treatment cycle.Results: Twenty-seven patients received CPT. Using the European Group for Blood and Marrow Transplantation criteria, we calculated the overall response rate of 33.3% with 1 near-complete response(n CR) and 8 partial responses(PRs). The clinical beneit rate(48.1%) included 1 nCR, 8 PRs, and 4 minimal responses. The most common treatmentrelated adverse events(TRAEs) were fever, aspartate aminotransferase elevation, alanine aminotransferase elevation, leucopenia, rash, neutropenia, and thrombocytopenia. We graded toxicity using the Common Toxicity Criteria for Adverse Events, version 3.0, and determined that 37.0% of patients had at least 1 grade 3–4 TRAE.Conclusions: CPT as a single agent can elicit a response in patients with RRMM and is well tolerated. Further clinical investigation is warranted.
文摘OBJECTIVE Though doxorubicin is highly activein the treatment of multiple myeloma, its toxicityprofile limits its therapeutic index. We performed thisstudy to evaluate the efficacy and safety of pegylatedliposomal doxorubicin (PLD, Caelyx^(?)), vincristine,and reduced-dose dexamethasone combinationtherapy in newly diagnosed multiple myeloma (MM)patients in a Chinese population.METHODS This was an open-label, single-armstudy in which newly diagnosed patients with MMreceived PLD 40 mg/m^2 intravenously on Day 1,vincristine 1.4 mg/m^2 intravenously (maximum 2 mg)on Day 1, and 40 mg of dexarnethasone (intravenouslyor orally) from Day 1 to Day 4. Treatment wasrepeated every 28 days for at least 4 cycles.RESULTS In the intent-to-treat (ITT) analysis, theoverall response rate was 68.29%, and the completeremission rate was 10.98%. The incidence of alladverse events was 46.34%. The most commonnon-hematologic toxicities were palmar-plantarerythrodysesthesia (13.4%) and stomatitis (6.1%).CONCLUSION PLD, vincristine, and a reduceddosedexamethasone combination (DVd) is aneffective and safe regimen in newly diagnosed MMpatients in a Chinese population.
基金the National Natural Science Foundation of China(81970187,82170193,81920108006,and 81900203)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2M-C&T-B-081).
文摘Rituximab maintenance(RM)prolongs the progression-free survival(PFS)of responding patients with follicular lymphoma(FL),but the maintenance efficacy in different Follicular Lymphoma International Prognostic Index(FLIPI)risk group is still confusing.We performed a retrospective analysis of the effect of RM treatments in patients with FL responding to induction therapy based on their FLIPI risk assessment carried out prior to treatment.We identified 93 patients between 2013 and 2019 who received RM every 3 months for≥4 doses(RM group),and 60 patients who did not accept RM or received rituximab less than 4 doses(control group).After a median follow-up of 39 months,neither median overall survival(OS)nor PFS was reached for the entire population.The PFS was significantly prolonged in the RM group compared to the control group(median PFS NA vs 83.1 months,P=.00027).When the population was divided into the 3 FLIPI risk groups,the PFS differed significantly(4-year PFS rates,97.5%vs 88.8%vs 72.3%,P=.01)according to group.There was no significant difference in PFS for FLIPI low-risk patients with RM compared to the control group(4-year PFS rates,100%vs 93.8%,P=.23).However,the PFS of the RM group was significantly prolonged for FLIPI intermediate-risk(4-year PFS rates,100%vs 70.3%,P=.00077)and high-risk patients(4-year PFS rates,86.7%vs 57.1%,P=.023).These data suggest that standard RM significantly prolongs the PFS of patients assigned to intermediate-and high-risk FLIPI groups but not to low-risk FLIPI group,and pending larger-scale studies to validate.
基金supported by the National Natural Science Foundation of China(Nos.81920108006,82270218)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Nos.2021-I2M-1-041,2022-I2M-1-022).
文摘To the Editor:Multiple myeloma(MM)is a plasma cell disorder characterized by heterogeneous features.^([1])Accurate risk stratification could predict diverse prognoses of patients with myeloma and attain risk-adapted therapy to extend their lifespan.Recently,the European Myeloma Network(EMN)conducted a large retrospective analysis involving more than 7000 patients with myeloma and developed a new risk model defined as the Second Revision of International Staging System(R2-ISS),with excellent risk distribution among patients enrolled in clinical trials.^([2])The R2-ISS stratifications were based on weighted risk scores of different prognostic factors:ISS II 1.0 point,ISS III 1.5 points,del(17p)1.0 point,elevated lactate dehydrogenase(LDH)1.0 point,t(4;14)1.0 point,and 1q21+0.5 points.
基金National Nature Science Foundation of China(Nos.81900203,81970187,82170193,and 81920108006)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(Nos.2022-12M-1-022,2021-I2M-C&T-B-081)
文摘To the Editor:As a rare indolent B cell non-Hodgkin lymphoma,lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia(LPL/WM)has unique clinical and biological characteristics.[1]However,due to the difficulties in obtaining tumor metaphase for karyotyping and slow cell proliferation,only very few studies have detected the cytogenetic aberration of LPL/WM.[2,3]In addition,6q deletion is the most common cytogenetic aberration in WM,with an incidence rate of about 50%.[2]Nevertheless,other cytogenetic aberrations remain largely unclear,and the prognostic role of cytogenetic aberrations needs to be further explored.In the present study,we systematically analyzed 305 LPL/WM cases in China,focusing on the characteristics and cytogenetic aberrations in Chinese patients.
基金supported by the National Natural Science Foundation of China(82170194,81920108006,82270175)the CAMS Innovation Fund for Medical Sciences(CIFMS 2021-I2M-1-040,CIFMS 2022-I2M-022).
文摘MicroRNAs(MiRNAs)carried by exosomes play pivotal roles in the crosstalk between cell components in the tumor microenvironment.Our study aimed at identifying the expression profile of exosomal miRNAs(exo-miRNAs)in the serum of multiple myeloma(MM)patients and investigating the regulation networks and their potential functions by integrated bioinformatics analysis.Exosomes in serum from 19 newly diagnosed MM patients and 9 healthy donors were isolated and the miRNA profile was investigated by small RNA sequencing.Differential expression of exo-miRNAs was calculated and target genes of miRNAs were predicted.CytoHubba was applied to identify the hub miRNAs and core target genes.The LASSO Cox regression model was used to develop the prognostic model,and the ESTIMATE immune score was calculated to investigate the correlation between the model and immune status in MM patients.The top six hub differentially expressed serum exo-miRNAs were identified.513 target genes of the six hub exo-miRNAs were confirmed to be differentially expressed in MM cells in the Zhan Myeloma microarray dataset.Functional enrichment analysis indicated that these target genes were mainly involved in mRNA splicing,cellular response to stress,and deubiquitination.13 core exo-miRNA target genes were applied to create a novel prognostic signature to provide risk stratification for MM patients,which is associated with the immune microenvironment of MM patients.Our study comprehensively investigated the exo-miRNA profiles in MM patients.A novel prognostic signature was constructed to facilitate the risk stratification of MM patients with distinct outcomes.
