Multiple myeloma is a complex and challenging blood cancer,particularly in cases where the disease has relapsed or become resistant to treatment.These situations often have a significant impact on both patient surviva...Multiple myeloma is a complex and challenging blood cancer,particularly in cases where the disease has relapsed or become resistant to treatment.These situations often have a significant impact on both patient survival and quality of life.Over recent years,advances in precision medicine and translational medicine have brought about a shift in treatment strategies,moving toward more personalized and targeted approaches.This review highlights the latest developments in the management of refractory and relapsed multiple myeloma,focusing on the current state of precision diagnosis and treatment,the role of translational medicine,and potential future directions in research.By reviewing key studies and clinical trial data,we aim to offer fresh perspectives and strategies that could improve clinical outcomes.展开更多
CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immuno...CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immunochemotherapy.The incidence of CD5+DLBCL is 5%–10%among DLBCL patients1.展开更多
Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for...Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for DLBCL is chemo-immunotherapy with rituximab,cyclophos-phamide,doxorubicin,vincristine,and prednisone,which cures 50%-60% of patients2.展开更多
Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have m...Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.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
Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy...Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.展开更多
BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2...BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.展开更多
BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clini...BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clinical outcome.Although L-asparaginase-based chemotherapy has improved the response rates of relapsed/refractory(R/R) ENKL,relapse occurs in up to 50% of patients with disseminated disease.CASE SUMMARY Immune evasion has emerged as a critical pathway for survival in ENKL and may be effectuated via STAT3-driven upregulation of programmed cell death ligand 1(PD-L1) or other molecular pathways.Anti-PD-1 is effective for R/R ENKL with EBV-driven upregulation of PD-L1 expression.Anti-PD-1 combined with decitabine showed positive preliminary results in a patient with R/R ENKL and resistance to anti-PD-1.CONCLUSION The treatment experience,in this case,demonstrated the potential ability of decitabine combined with PD-1 inhibitor to treat R/R ENKL,thus providing a new treatment strategy for this tumor.展开更多
Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high...BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes.Despite the administration of immunotherapeutic agents,in particular bortezomib and daratumumab,which have improved the outcomes of AL amyloidosis,antiplasma cell therapy remains suboptimal for some patients.CASE SUMMARY We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy.He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen.The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion,in which flow cytometry analysis showed abnormal plasma cells.After two cycles of this regimen,the pleural effusion was controlled effectively with no recurrence.CONCLUSION This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.展开更多
BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)...BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.展开更多
Objective:To investigate the clinical efficacy and safety of ixazomib in the treatment of relapsed/refractory multiple myeloma(RRMM).Methods:The clinical data of 20 patients with RRMM admitted to the hospital from Jan...Objective:To investigate the clinical efficacy and safety of ixazomib in the treatment of relapsed/refractory multiple myeloma(RRMM).Methods:The clinical data of 20 patients with RRMM admitted to the hospital from January 2020 to January 2022 were analyzed retrospectively.All patients were treated with ixazomib-based chemotherapy regimen(IRD regimen 13 cases;ID regimen 7 cases).The objective response rate(ORR)and adverse events(AEs)were observed.Results:All 20 patients received two to seven courses of treatment,in which the median was three courses.One patient had CR,four patients had VGPR,seven patients had PR,two patients had SD,and six patients had PD.The ORR was 60.00%(12/20),and 25.00%(5/20)of them had VGPR or more.The ORR of patients with previous treatment lines≥3,ISS stage III,and high-risk cytogenetic was lower than that of patients with previous treatment lines<3,ISS stage I/II,and low-risk cytogenetics.The main AEs include anemia,thrombocytopenia,neutropenia,nausea and vomiting,diarrhea,constipation,and respiratory tract infection,most of which are grade I/II.Conclusion:Ixazomib is effective in the treatment of RRMM in some patients,and the AEs are controllable.Patients who had received less than 3 lines of treatment in the past,with ISS stage I to II and low-risk cytogenetics had better treatment effect.展开更多
Objective: to investigate the clinical effect of relapsed refractory acute myeloid leukemia. Methods: 160 patients with relapsed refractory acute myeloid leukemia in our hospital from January 2019 to January 2021 were...Objective: to investigate the clinical effect of relapsed refractory acute myeloid leukemia. Methods: 160 patients with relapsed refractory acute myeloid leukemia in our hospital from January 2019 to January 2021 were randomly divided into the observation group and the control group. 80 patients in the control group were treated with CAG treatment scheme, and 80 patients in the observation group were treated with decitabine on the basis of CAG treatment scheme. The final treatment effect of the two groups of patients was compared. Results: the therapeutic effect of the observation group was better than that of the control group. In contrast, the effective rate of 82.50% in the observation group was higher than that of 67.50% in the other group;There was no difference in the incidence of adverse reactions between the two groups. Conclusion: CAG combined with decitabine is effective in the treatment of relapsed refractory acute myeloid leukemia. The quality of life of the patients can be effectively improved. Compared with the previous patients, they have a higher degree of life comfort. The disease control effect of the patients is better, and the adverse reactions are also within the controllable range.展开更多
To the Editor:In China,multiple myeloma(MM)has a crude prevalence of 7 per 100,000 population and an incidence of 1.6 per 100,000 population.[1]The term“1q21 abnormality”refers to genetic alterations including delet...To the Editor:In China,multiple myeloma(MM)has a crude prevalence of 7 per 100,000 population and an incidence of 1.6 per 100,000 population.[1]The term“1q21 abnormality”refers to genetic alterations including deletions,duplications,and amplifications in the 1q21 region of chromosome 1.Gain or amplification of 1q21(1q21+),which refers to an additional copy or multiple copies of genetic material in the long arm of chromosome 1 at position 21,is a well-documented abnormality that correlates with adverse clinical outcomes in patients with MM and has been demonstrated to be associated with poor prognosis,drug resistance,and disease progression in newly diagnosed MM(NDMM)and relapsed/refractory MM(RRMM).[2]However,treatment options specifically for 1q21+patients have seldom been recommended in guidelines due to the lack of clinical data,except for the 2018 Mayo Stratification of Myeloma and Risk-adapted Therapy(mSMART)3.0,which makes recommendations for transplant-eligible NDMM patients.This study aimed to evaluate the effectiveness of treatment regimens for RRMM with 1q21+and to review relevant studies.展开更多
Improving the outcome of relapsed or refractory diffuse large B-cell lymphoma(R/R DLBCL)remained an unmet need.The aim of this single-center,phase 2 trial was to evaluate the efficacy and safety of genetic subtype-gui...Improving the outcome of relapsed or refractory diffuse large B-cell lymphoma(R/R DLBCL)remained an unmet need.The aim of this single-center,phase 2 trial was to evaluate the efficacy and safety of genetic subtype-guided immunochemotherapy(R-ICE-X)in patients with R/R DLBCL:R-ICE-zanubrutinib for MCD-like and BN2-like,R-ICE-lenalidomide for N1-like and NOS,R-ICE-decitabine for TP53^(Mut),R-ICE-chidamide for EZB-like,and R-ICE-tofacitinib for ST2-like subtype.Enrolled patients were treated with assigned regimens for three cycles,and then responders were treated with autologous hematopoietic stem cell transplantation(ASCT)or 3 cycles of R-ICE-X consolidation and lenalidomide maintenance.The primary endpoint was the complete response(CR)rate.展开更多
Simultaneously targeting key pathogenic drivers and remodeling of the tumor microenvironment represents a critical therapeutic strategy for relapsed or refractory(r/r)multiple myeloma(MM)and lymphoma.Purinostat mesyla...Simultaneously targeting key pathogenic drivers and remodeling of the tumor microenvironment represents a critical therapeutic strategy for relapsed or refractory(r/r)multiple myeloma(MM)and lymphoma.Purinostat mesylate(PM),a highly selective HDAC I/II binhibitor,exhibits excellent antitumor activity in MM and lymphoma cell lines and mouse models,outperforming the pan-HDAC inhibitor panobinostat or first-line/second-line multi-drug combinations.Different from panobinostat,bulk RNA-seq analysis revealed that PM suppressed essential tumor survival factors and triggered inflammation and interferon responses.The scRNA-seq of 5TMM models further indicated that PM enhanced antitumor immunity by boosting monocyte-and T cell-mediated immune responses.In a phase I trial(NCT05526313;N=29)of PM at doses up to 15 mg/m2,treatment-related Grade≥3 adverse events predominantly comprised hematologic toxicities:thrombocytopenia(75.9%),neutropenia(55.2%),leukopenia(41.4%),and lymphopenia(31.0%),with no dose-limiting toxicities observed.PM monotherapy achieved a disease control rate of 72.7%(8/11)and an objective response rate(ORR)of 9.1%(1/11)in r/r MM.Notably,r/r lymphoma patients showed an ORR of 61.6%(11/18),particularly reaching 63.6%(7/11)with 6 complete responses in diffuse large B-cell lymphoma(DLBCL).Treatment responders exhibited enhanced immune activation,with elevated CD3+CD8+T cells and increased cytokine levels,such as IFN-γand CXCL10.Overall,PM is safe and moderately effective in MM,but highly effective in lymphoma.Additionally,PM combined with pomalidomide and dexamethasone showed strong synergistic activity in r/r MM treatment.These findings support further openlabel,multicenter phase Ib/IIa trials of PM combination therapy with immunomodulators for r/r MM,as well as phase II monotherapy trials for r/r DLBCL and r/r T-cell lymphoma.展开更多
Autologous stem cell transplantation(ASCT)and chimeric antigen receptor T-cell(CAR-T)therapy represent pivotal treatments for hematologic malignancies,each with distinct strengths and limitations.ASCT reduces tumor bu...Autologous stem cell transplantation(ASCT)and chimeric antigen receptor T-cell(CAR-T)therapy represent pivotal treatments for hematologic malignancies,each with distinct strengths and limitations.ASCT reduces tumor burden through myeloablative conditioning but remains susceptible to relapse,while CAR-T therapy precisely targets malignant cells but encounters challenges,including cytokine release syndrome(CRS),immune effector cell-associated neurotoxicity syndrome(ICANS),and limited persistence.Emerging evidence suggests that combining ASCT with CAR-T therapy yields synergistic effects.ASCT reshapes the immune microenvironment,lowers immunosuppressive cells and CRS risk,while CAR-T eliminates residual disease and promotes immune recovery.Clinical trials in relapsed/refractory B-cell lymphomas and multiple myeloma demonstrate complete remission rates(CRR)of 72%-100%and two-year progression-free survival(PFS)rates of 59%-83%,with severe CRS/ICANS incidences below 10%.However,the precise mechanisms underlying this synergy,optimal timing of CAR-T infusion after ASCT,and ideal dosing regimens require further definition.Future research should prioritize large-scale,randomized controlled trials and establish standardized protocols for toxicity management to maximize therapeutic benefits.By integrating the complementary strengths of ASCT and CAR-T,this combination strategy represents a promising approach for improving outcomes in high-risk hematologic malignancies;however,additional studies are necessary to validate its efficacy and expand its clinical applicability.展开更多
To the Editor:Approximately 30–50%of diffuse large B-cell lymphoma(DLBCL)patients experience disease progression or relapse after chimeric antigen receptor T(CAR-T)cell therapy,and combination therapy may be a feasib...To the Editor:Approximately 30–50%of diffuse large B-cell lymphoma(DLBCL)patients experience disease progression or relapse after chimeric antigen receptor T(CAR-T)cell therapy,and combination therapy may be a feasible strategy to reduce the risk of relapse.Malignant B cells maintain B-cell receptor(BCR)expression on the cell surface and benefit from the proliferation,survival,and migration pathways triggered by BCR.Bruton tyrosine kinase(BTK)is an important component of the BCR signaling pathway,and the anti-lymphoma function generated by inhibiting the BTK pathway makes it a promising therapeutic target in B-cell malignant tumors and inflammatory diseases.展开更多
Background:Treatment with chimeric antigen receptor-T(CAR-T)cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia(R/R B-ALL),although the process of preparing...Background:Treatment with chimeric antigen receptor-T(CAR-T)cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia(R/R B-ALL),although the process of preparing for this therapy usually takes a long time.We have recently created CD19 Fast-CAR-T(F-CAR-T)cells,which can be produced within a single day.The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL.Methods:A multicenter,retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted.Overall,23 patients were administered with innovative CD19 F-CAR-T cells(F-CAR-T group),whereas 21 patients were given CD19 conventional CAR-T cells(C-CAR-T group).We compared the rates of complete remission(CR),minimal residual disease(MRD)-negative CR,leukemia-free survival(LFS),overall survival(OS),and the incidence of cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)between the two groups.Results:Compared with the C-CAR-T group,the F-CAR-T group had significantly higher CR and MRD-negative rates(95.7%and 91.3%,respectively;71.4%and 66.7%,respectively;P=0.036 and P=0.044).No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups:the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8%and 43.5%vs.38.1%and 23.8%(P=0.384 and P=0.216),while the 1-year and 2-year OS rates were 65.2%and 56.5%vs.52.4%and 47.6%(P=0.395 and P=0.540).Additionally,among CR patients who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)following CAR-T-cell therapy,there were no significant differences in the 1-year or 2-year LFS or OS rates:57.1%and 50.0%vs.47.8%and 34.8%(P=0.506 and P=0.356),64.3%and 57.1%vs.65.2%and 56.5%(P=0.985 and P=0.883),respectively.The incidence of CRS was greater in the F-CAR-T group(91.3%)than in the C-CAR-T group(66.7%)(P=0.044).The incidence of ICANS was also greater in the F-CAR-T group(30.4%)than in the C-CAR-T group(9.5%)(P=0.085),but no treatment-related deaths occurred in the two groups.Conclusion:Compared with C-CAR-T-cell therapy,F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS.Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.展开更多
The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （N...The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.展开更多
基金supported by grants from the 925th Science Foundation(Grant Nos.2023-3 and 2024-2/3).
文摘Multiple myeloma is a complex and challenging blood cancer,particularly in cases where the disease has relapsed or become resistant to treatment.These situations often have a significant impact on both patient survival and quality of life.Over recent years,advances in precision medicine and translational medicine have brought about a shift in treatment strategies,moving toward more personalized and targeted approaches.This review highlights the latest developments in the management of refractory and relapsed multiple myeloma,focusing on the current state of precision diagnosis and treatment,the role of translational medicine,and potential future directions in research.By reviewing key studies and clinical trial data,we aim to offer fresh perspectives and strategies that could improve clinical outcomes.
基金supported by funding from the National Natural Science Foundation of China(Grant No.82170167 to Xiaoxi Zhou and Grant No.82300226 to Hui Luo)。
文摘CD5-positive(CD5+)diffuse large B-cell lymphoma(DLBCL)represents a special subgroup of DLBCL with a more aggressive disease course and is more likely to develop into relapsed/refractory(r/r)DLBCL in response to immunochemotherapy.The incidence of CD5+DLBCL is 5%–10%among DLBCL patients1.
基金sponsored by Shanghai Roche Pharmaceuticals Ltd.
文摘Diffuse large B-cell lymphoma(DLBCL),the most common subtype of non-Hodgkin’s lymphoma(NHL)worldwide,accounts for 39% and 44% of nodal and extranodal NHL cases in China,respectively1.Standard first-line treatment for DLBCL is chemo-immunotherapy with rituximab,cyclophos-phamide,doxorubicin,vincristine,and prednisone,which cures 50%-60% of patients2.
基金supported by grant from the National Natural Science Foundation of China(Grant No.82300231).
文摘Multiple myeloma(MM),one of the most common hemato logical neoplasms worldwide,originates from malignant plasma cells in the bone marrow.MM remains an incurable disease,although continued treatment advancements have markedly increased overall survival.Many patients with MM eventually experience relapse or become treatment-refractory1.Patients with relapsed or refractory multiple myeloma(RRMM)become progressively more challenging to manage and have poor prognosis2.
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.
基金the National Natural Science Foundation of China(No.81873452)the Clinical Research Program of Huazhong University of Science and Technology Affiliated Tongji Hospital(No.2020003).
文摘Anti-B cell maturation antigen(BCMA)chimeric antigen receptor(CAR)T-cell therapyis effective and well-tolerated for refractory or relapsed multiple myeloma(RRMM).The purposcof the present study was to analyze efficacy in RRMM patients with renal impairment treated byanti-BCMA CAR-T cell therapy.A total of 59 RRMM patients were selected,and divided intoimpaired renal function(lRF)group[basclinc cstimated giomerular filtration rate(eSFR)<90 m/min/1.73 m^2(n=18)]and normal renal function(NRF)group(baseline eGFR≥90 mL/min/1.73 m,n=41).For patients with IRF,eGFR at the 6th month post-CAR-T cells infusion was significantlyhigher than the baseline(P<0.05).The multivariate analysis showed that light chain type and beta-2 micro-globulin(bcta-2M)were associated factors with the decrease of serum creatinine.Medianprogression-free survival(PFS)in the NRF group and IRF group was 266 days and 181 daysrespectively.Overall survival(OS)in the NRF group and lRF group was 877 days and 238 daysrespectively.There was no significant difference in the objective response rate(ORR)between thelRF group and the NRF group.It is suggested that CAR-T cells therapy could improve the renalfunction during the treatment of RRMM.The renal function could be more significantly improvedin RRMM patients with light chain type than with other types.
文摘BACKGROUND Conventional therapies for primary plasma cell leukemia(pPCL)are usually ineffective,with a short remission time with the use of multiple myeloma medications,showing aggressiveness of pPCL.B-cell lymphoma-2 inhibitor venetoclax is usually used for relapsed/refractory multiple myeloma(RRMM)with t(11;14).There are very few studies published on the use of venetoclax in pPCL without t(11;14).Similarly,histone deacetylase inhibitors are considered effective for the treatment of RRMM,but there are no reports on their use in pPCL.CASE SUMMARY A 57-year-old woman with severe anemia,thrombocytopenia,multiple bone destruction,impaired renal function,and 42.7%of peripheral plasma cells is reported.After multiple chemotherapy regimens and chimeric antigen receptor Tcell treatment,the disease progressed again.The patient had very good partial response and was maintained for a long time on venetoclax in combination with chidamide and dexamethasone therapy.CONCLUSION The success of venetoclax-chidamide-dexamethasone combination therapy in achieving a very good partial response suggested that it can be used for refractory/relapsed pPCL patients who have been exhausted with the use of various drug combinations and had poor survival outcomes.
基金Supported by the Medical Health Science and Technology Project of Zhejiang Province Health Commission,No.2020376298。
文摘BACKGROUND Extranodal natural killer/T cell lymphoma,nasal type(ENKL) is a highly aggressive malignancy characterized by its association with Epstein-Barr virus(EBV) and extranodal involvement,which shows a poor clinical outcome.Although L-asparaginase-based chemotherapy has improved the response rates of relapsed/refractory(R/R) ENKL,relapse occurs in up to 50% of patients with disseminated disease.CASE SUMMARY Immune evasion has emerged as a critical pathway for survival in ENKL and may be effectuated via STAT3-driven upregulation of programmed cell death ligand 1(PD-L1) or other molecular pathways.Anti-PD-1 is effective for R/R ENKL with EBV-driven upregulation of PD-L1 expression.Anti-PD-1 combined with decitabine showed positive preliminary results in a patient with R/R ENKL and resistance to anti-PD-1.CONCLUSION The treatment experience,in this case,demonstrated the potential ability of decitabine combined with PD-1 inhibitor to treat R/R ENKL,thus providing a new treatment strategy for this tumor.
基金the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
文摘BACKGROUND Immunoglobulin light chain(AL)amyloidosis is a rare disease characterized by deposition of ALs essentially in any organ or tissue,with cardiac involvement being very frequent(61%).Early diagnosis is of high importance because early initiation of treatment in AL amyloidosis may improve outcomes.Despite the administration of immunotherapeutic agents,in particular bortezomib and daratumumab,which have improved the outcomes of AL amyloidosis,antiplasma cell therapy remains suboptimal for some patients.CASE SUMMARY We report the case of a 55-year-old man presenting with heart failure who was diagnosed with cardiac AL amyloidosis by an endomyocardial biopsy.He experienced a short-term hematological remission with no organ response after being administered a bortezomib-daratumumab containing regimen.The treatment was switched to pomolidomide due to pulmonary involvement and progressive pleural effusion,in which flow cytometry analysis showed abnormal plasma cells.After two cycles of this regimen,the pleural effusion was controlled effectively with no recurrence.CONCLUSION This case emphasizes the crucial role of endomyocardial biopsy in early diagnosis of cardiac amyloidosis and suggests that pomolidomide may be an effective treatment for patients with AL amyloidosis that is relapsed/refractory to both bortezomib and daratumumab.
文摘BACKGROUND Chimeric antigen receptor T cell(CART)therapy has benefited many refractory lymphoma patients,but some patients experience poor effects.Previous studies have shown that programmed cell death protein-1(PD-1)inhibitors can improve and prolong the therapeutic effect of CAR-T cell treatment.CASE SUMMARY A 61-year-old male presented with 15-d history of diarrhea and lower-limb edema.A large mass was detected in the pelvis,and pathology indicated non-Hodgkin diffuse large B-cell lymphoma.After three cycles of the R-CHOP chemotherapeutic regimen,the patient showed three subcutaneous nodules under the left armpit and both sides of the cervical spine.Pathological examination of the nodules indicated DLBCL again.The patient was diagnosed with relapsed and refractory diffuse large B-cell lymphoma.We recommended CAR-T cell treatment.Before treatment,the patient’s T cell function and expression of immune detection points were tested.Expression of PD-1 was obviously increased(52.7%)on cluster of differentiation(CD)3+T cells.The PD-1 inhibitor(3 mg/kg)was infused prior to lymphodepleting chemotherapy with fludarabine and cyclophosphamide.CAR-CD19 T cells of 3×10^(6)/kg and CAR-CD22 T cells 1×10^(6)/kg were infused,respectively.The therapeutic effect was significant,and the deoxyribonucleic acid copy numbers of CAR-CD19 T cells and CAR-CD22 T cells were stable.Presently,the patient has been disease-free for more than 12 mo.CONCLUSION This case suggests that the combination of PD-1 inhibitors and CAR-T cellsimproved therapeutic efficacy in B-cell lymphoma.
文摘Objective:To investigate the clinical efficacy and safety of ixazomib in the treatment of relapsed/refractory multiple myeloma(RRMM).Methods:The clinical data of 20 patients with RRMM admitted to the hospital from January 2020 to January 2022 were analyzed retrospectively.All patients were treated with ixazomib-based chemotherapy regimen(IRD regimen 13 cases;ID regimen 7 cases).The objective response rate(ORR)and adverse events(AEs)were observed.Results:All 20 patients received two to seven courses of treatment,in which the median was three courses.One patient had CR,four patients had VGPR,seven patients had PR,two patients had SD,and six patients had PD.The ORR was 60.00%(12/20),and 25.00%(5/20)of them had VGPR or more.The ORR of patients with previous treatment lines≥3,ISS stage III,and high-risk cytogenetic was lower than that of patients with previous treatment lines<3,ISS stage I/II,and low-risk cytogenetics.The main AEs include anemia,thrombocytopenia,neutropenia,nausea and vomiting,diarrhea,constipation,and respiratory tract infection,most of which are grade I/II.Conclusion:Ixazomib is effective in the treatment of RRMM in some patients,and the AEs are controllable.Patients who had received less than 3 lines of treatment in the past,with ISS stage I to II and low-risk cytogenetics had better treatment effect.
文摘Objective: to investigate the clinical effect of relapsed refractory acute myeloid leukemia. Methods: 160 patients with relapsed refractory acute myeloid leukemia in our hospital from January 2019 to January 2021 were randomly divided into the observation group and the control group. 80 patients in the control group were treated with CAG treatment scheme, and 80 patients in the observation group were treated with decitabine on the basis of CAG treatment scheme. The final treatment effect of the two groups of patients was compared. Results: the therapeutic effect of the observation group was better than that of the control group. In contrast, the effective rate of 82.50% in the observation group was higher than that of 67.50% in the other group;There was no difference in the incidence of adverse reactions between the two groups. Conclusion: CAG combined with decitabine is effective in the treatment of relapsed refractory acute myeloid leukemia. The quality of life of the patients can be effectively improved. Compared with the previous patients, they have a higher degree of life comfort. The disease control effect of the patients is better, and the adverse reactions are also within the controllable range.
文摘To the Editor:In China,multiple myeloma(MM)has a crude prevalence of 7 per 100,000 population and an incidence of 1.6 per 100,000 population.[1]The term“1q21 abnormality”refers to genetic alterations including deletions,duplications,and amplifications in the 1q21 region of chromosome 1.Gain or amplification of 1q21(1q21+),which refers to an additional copy or multiple copies of genetic material in the long arm of chromosome 1 at position 21,is a well-documented abnormality that correlates with adverse clinical outcomes in patients with MM and has been demonstrated to be associated with poor prognosis,drug resistance,and disease progression in newly diagnosed MM(NDMM)and relapsed/refractory MM(RRMM).[2]However,treatment options specifically for 1q21+patients have seldom been recommended in guidelines due to the lack of clinical data,except for the 2018 Mayo Stratification of Myeloma and Risk-adapted Therapy(mSMART)3.0,which makes recommendations for transplant-eligible NDMM patients.This study aimed to evaluate the effectiveness of treatment regimens for RRMM with 1q21+and to review relevant studies.
基金supported by research funding from the National Key R&D Program of China(2023YFC3605704,2022YFC2502600)the National Natural Science Foundation of China(82130004,82170178,82200201,82070204)+6 种基金the Multicenter Clinical Research Project by Shanghai Jiao Tong University School of Medicine(DLY201601)the Chang Jiang Scholars Program,the Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR1032B)Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(20152206,20152208)the Multicenter Hematology-Oncology Program Evaluation System(M-HOPES)the Shanghai Sailing Program(23YF1423700)the Collaborative Innovation Center of Systems Biomedicinethe Samuel Waxman Cancer Research Foundation.
文摘Improving the outcome of relapsed or refractory diffuse large B-cell lymphoma(R/R DLBCL)remained an unmet need.The aim of this single-center,phase 2 trial was to evaluate the efficacy and safety of genetic subtype-guided immunochemotherapy(R-ICE-X)in patients with R/R DLBCL:R-ICE-zanubrutinib for MCD-like and BN2-like,R-ICE-lenalidomide for N1-like and NOS,R-ICE-decitabine for TP53^(Mut),R-ICE-chidamide for EZB-like,and R-ICE-tofacitinib for ST2-like subtype.Enrolled patients were treated with assigned regimens for three cycles,and then responders were treated with autologous hematopoietic stem cell transplantation(ASCT)or 3 cycles of R-ICE-X consolidation and lenalidomide maintenance.The primary endpoint was the complete response(CR)rate.
基金funded by the Sichuan Province“14th Five-Year Plan”Life and Health Major Science and Technology Project(2022ZDZX0027)Key Project of Chengdu(2021-YF08-00002-GX)+3 种基金the Incubation Program for Clinical Trials of West China Hospital(19HXFH030)the National Natural Science Foundation of China(82104211)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD23020,ZYJC21007)National Key Research and Development Program of China(2022YFC2502600,2022YFC2502603).
文摘Simultaneously targeting key pathogenic drivers and remodeling of the tumor microenvironment represents a critical therapeutic strategy for relapsed or refractory(r/r)multiple myeloma(MM)and lymphoma.Purinostat mesylate(PM),a highly selective HDAC I/II binhibitor,exhibits excellent antitumor activity in MM and lymphoma cell lines and mouse models,outperforming the pan-HDAC inhibitor panobinostat or first-line/second-line multi-drug combinations.Different from panobinostat,bulk RNA-seq analysis revealed that PM suppressed essential tumor survival factors and triggered inflammation and interferon responses.The scRNA-seq of 5TMM models further indicated that PM enhanced antitumor immunity by boosting monocyte-and T cell-mediated immune responses.In a phase I trial(NCT05526313;N=29)of PM at doses up to 15 mg/m2,treatment-related Grade≥3 adverse events predominantly comprised hematologic toxicities:thrombocytopenia(75.9%),neutropenia(55.2%),leukopenia(41.4%),and lymphopenia(31.0%),with no dose-limiting toxicities observed.PM monotherapy achieved a disease control rate of 72.7%(8/11)and an objective response rate(ORR)of 9.1%(1/11)in r/r MM.Notably,r/r lymphoma patients showed an ORR of 61.6%(11/18),particularly reaching 63.6%(7/11)with 6 complete responses in diffuse large B-cell lymphoma(DLBCL).Treatment responders exhibited enhanced immune activation,with elevated CD3+CD8+T cells and increased cytokine levels,such as IFN-γand CXCL10.Overall,PM is safe and moderately effective in MM,but highly effective in lymphoma.Additionally,PM combined with pomalidomide and dexamethasone showed strong synergistic activity in r/r MM treatment.These findings support further openlabel,multicenter phase Ib/IIa trials of PM combination therapy with immunomodulators for r/r MM,as well as phase II monotherapy trials for r/r DLBCL and r/r T-cell lymphoma.
基金supported by funding from the National KeyR&D Program of China(No.2022YFC2502604)the National Natural Science Foundation of China(No.82470194)+1 种基金the CAMS Innovation Fund for Medical Sciences(CIFMS)(No.2024-I2M-3-021)the ChenXiaoping Foundation for the development of Science and Technology of Hubei Province(No.CXPJJH122001-2221)。
文摘Autologous stem cell transplantation(ASCT)and chimeric antigen receptor T-cell(CAR-T)therapy represent pivotal treatments for hematologic malignancies,each with distinct strengths and limitations.ASCT reduces tumor burden through myeloablative conditioning but remains susceptible to relapse,while CAR-T therapy precisely targets malignant cells but encounters challenges,including cytokine release syndrome(CRS),immune effector cell-associated neurotoxicity syndrome(ICANS),and limited persistence.Emerging evidence suggests that combining ASCT with CAR-T therapy yields synergistic effects.ASCT reshapes the immune microenvironment,lowers immunosuppressive cells and CRS risk,while CAR-T eliminates residual disease and promotes immune recovery.Clinical trials in relapsed/refractory B-cell lymphomas and multiple myeloma demonstrate complete remission rates(CRR)of 72%-100%and two-year progression-free survival(PFS)rates of 59%-83%,with severe CRS/ICANS incidences below 10%.However,the precise mechanisms underlying this synergy,optimal timing of CAR-T infusion after ASCT,and ideal dosing regimens require further definition.Future research should prioritize large-scale,randomized controlled trials and establish standardized protocols for toxicity management to maximize therapeutic benefits.By integrating the complementary strengths of ASCT and CAR-T,this combination strategy represents a promising approach for improving outcomes in high-risk hematologic malignancies;however,additional studies are necessary to validate its efficacy and expand its clinical applicability.
文摘To the Editor:Approximately 30–50%of diffuse large B-cell lymphoma(DLBCL)patients experience disease progression or relapse after chimeric antigen receptor T(CAR-T)cell therapy,and combination therapy may be a feasible strategy to reduce the risk of relapse.Malignant B cells maintain B-cell receptor(BCR)expression on the cell surface and benefit from the proliferation,survival,and migration pathways triggered by BCR.Bruton tyrosine kinase(BTK)is an important component of the BCR signaling pathway,and the anti-lymphoma function generated by inhibiting the BTK pathway makes it a promising therapeutic target in B-cell malignant tumors and inflammatory diseases.
基金This work was supported by grants the National Natural Science Foundation of China(Nos.82341201 and 82370181)the National Key R&D Program of China(Nos.2022YFA1103300 and 2022YFA1103304)+1 种基金the Chongqing Science and Health Joint Medical Research Project(No.2024QNXM025)the Special Project for Talent Construction in Xinqiao Hospital of Army Medical University(No.2022XKRC001)
文摘Background:Treatment with chimeric antigen receptor-T(CAR-T)cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia(R/R B-ALL),although the process of preparing for this therapy usually takes a long time.We have recently created CD19 Fast-CAR-T(F-CAR-T)cells,which can be produced within a single day.The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL.Methods:A multicenter,retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted.Overall,23 patients were administered with innovative CD19 F-CAR-T cells(F-CAR-T group),whereas 21 patients were given CD19 conventional CAR-T cells(C-CAR-T group).We compared the rates of complete remission(CR),minimal residual disease(MRD)-negative CR,leukemia-free survival(LFS),overall survival(OS),and the incidence of cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)between the two groups.Results:Compared with the C-CAR-T group,the F-CAR-T group had significantly higher CR and MRD-negative rates(95.7%and 91.3%,respectively;71.4%and 66.7%,respectively;P=0.036 and P=0.044).No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups:the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8%and 43.5%vs.38.1%and 23.8%(P=0.384 and P=0.216),while the 1-year and 2-year OS rates were 65.2%and 56.5%vs.52.4%and 47.6%(P=0.395 and P=0.540).Additionally,among CR patients who underwent allogeneic hematopoietic stem cell transplantation(allo-HSCT)following CAR-T-cell therapy,there were no significant differences in the 1-year or 2-year LFS or OS rates:57.1%and 50.0%vs.47.8%and 34.8%(P=0.506 and P=0.356),64.3%and 57.1%vs.65.2%and 56.5%(P=0.985 and P=0.883),respectively.The incidence of CRS was greater in the F-CAR-T group(91.3%)than in the C-CAR-T group(66.7%)(P=0.044).The incidence of ICANS was also greater in the F-CAR-T group(30.4%)than in the C-CAR-T group(9.5%)(P=0.085),but no treatment-related deaths occurred in the two groups.Conclusion:Compared with C-CAR-T-cell therapy,F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS.Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.
基金supported by the Science and Technology Planning Project of Beijing City (Z151100003915076)the National Natural Science Foundation of China (31270820, 81230061, 81472612, 81402566)+1 种基金the National Basic Science and Development Programme of China (2013BAI01B04)the Nursery Innovation Fund (15KMM50)
文摘The successes achieved by chimeric antigen receptor-modified T （CAR-T） cells in hematological malignancies raised the pos- sibility of their use in non-small lung cancer （NSCLC）. In this phase I clinical study （NCT01869166）, patients with epidermal growth factor receptor （EGFR）-positive （〉50% expression）, relapsed/refractory NSCLC received escalating doses of EGFR-targeted CAR-T cell infusions. The EGFR-targeted CAR-T cells were generated from peripheral blood after a 10 to 13-day in vitro expansion. Serum cytokines in peripheral blood and copy numbers of CAR-EGFR transgene in peripheral blood and in tissue biopsy were monitored periodically. Clinical responses were evaluated with RECISTI.1 and im- mune-related response criteria, and adverse events were graded with CTCAE 4.0. The EGFR-targeted CAR-T cell infusions were well-tolerated without severe toxicity. Of 11 evaluable patients, two patients obtained partial response and five had stable disease for two to eight months. The median dose of transfused CAR＋ T cells was 0.97x 10^7 cells kg J （interquar- tile range （IQR）, 0.45 to 1.09x 10^7 cells kg 1）. Pathological eradication of EGFR positive tumor cells after EGFR-targeted CAR-T cell treatment can be observed in tumor biopsies, along with the CAR-EGFR gene detected in tumor-infiltrating T cells in all four biopsied patients. The EGFR-targeted CAR-T cell therapy is safe and feasible for EGFR-positive advanced re- lapsed/refractory NSCLC.
