Refractory lymphoma treated with chimeric antigen receptor T cells combined with programmed cell death-1 inhibitor:A case report

BACKGROUND Diffuse large B-cell lymphoma(DLBCL)is a common aggressive non-Hodgkin's lymphoma(NHL),accounting for 30%-40%of adult NHL.Primary testicular(PT)lymphoma is an uncommon extranodal disease representing approximately 1%-2%of lymphoma.Approximately 30%–40%of patients are refractory to frontline therapy or relapse after complete remission.Refractory DLBCL responds poorly to other lines of chemotherapy,and experiences short-term survival.CASE SUMMARY We present a 41-year-old male patient who was diagnosed with PT-DLBCL.Further disease progression was observed after multiline chemotherapy.Chimeric antigen receptor T cells(CAR-T)therapy salvaged the patient.Unfortunately,a new mass was observed in the right adrenal area after six months.The patient was administered programmed cell death protein-1(PD-1)inhibitor therapy and maintained progression-free survival at more than 17 mo of follow-up.CONCLUSION Our findings support the potential benefit of CAR-T combined with PD-1 inhibitor therapies in this type of relapsed and refractory PT-DLBCL.

Programmed cell death protein-1 inhibitor combined with chimeric antigen receptor T cells in the treatment of relapsed refractory non- Hodgkin lymphoma: A case report

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.

Combination of atezolizumab and chidamide to maintain long-term remission in refractory metastatic extranodal natural killer/T-cell lymphoma:A case report

BACKGROUND The prognosis of refractory extranodal natural killer/T-cell lymphoma(ENKTL)is poor.Recent data have indicated that immune checkpoint blockade with a programmed cell death protein-1(PD-1)antibody in combination with administration of histone deacetylase inhibitors represents a potentially effective treatment strategy.Compared with PD-1 antibodies,programmed death-ligand 1 antibodies have fewer side effects.Here,we present a rare case of a patient with refractory metastatic ENKTL who achieved sustained remission of approximately 10 mo with minor adverse effects after combination therapy with atezolizumab,chidamide,and radiotherapy.CASE SUMMARY A 56-year-old woman underwent resection of a tumour in her left nasal cavity and was diagnosed with ENKTL(nasal type).Medical examination revealed tumours observed in the bilateral nasal mucosa,the subcutaneous soft tissue of the inner side of the left eye,the soft tissue of the nasopharynx,the bilateral tonsils,and the left preauricular,right hilar,bilateral neck lymph nodes and bone marrow.However,tomography/computed tomography showed increased metabolism of the bilateral nasal mucosa and subcutaneous soft tissue of the inner side of the left eye and newly increased metabolism of the left cervical lymph node after chemotherapy.Therefore,combination therapy with chidamide,atezolizumab,and radiotherapy was performed.Fortunately,the patient achieved a complete response following 10 mo of combination therapy.CONCLUSION The outcome in this case suggests that the combination of atezolizumab,chidamide,and radiotherapy is a promising regimen for treating refractory metastatic ENKTL following chemotherapy treatment failure.

Different sites of extranodal involvement may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptor T cell therapy

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T(CAR-T)cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma(r/r NHL)have not been well characterized.In this study,we found that the different sites of extranodal involvement may affect response,overall survival(OS),and progression-free survival(PFS)in patients with r/r NHL treated with anti-CD19 CAR-T cells.In a cohort of 32 treated patients,12(37.5%)and 8(25%)patients exhibited soft tissue lymphoma and bone marrow(BM)infiltrations,respectively,and 13(41%)patients exhibited infiltration at other sites.The factors that may affect prognosis were identified through multivariable analysis.As an independent risk factor,soft tissue infiltration was the only factor significantly correlated with adverse prognosis(P<0.05),whereas other factors did not reach statistical significance.Furthermore,the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy.PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone.Thus,anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.

Phase Ⅰ study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients

Anti-CD 19 chimeric antigen receptor(CAR)T cell therapy has shown impressive efficacy in treating B-cell malignancies.A single-center phase I dose-escalation study was conducted to evaluate the safety and efficacy of T cells transduced with CBM.CD19 CAR,a second-generation anti-CD19 CAR bearing 4-1BB costimulatory molecule,for the treatment of patients with refractory diffuse large B-cell lymphoma(DLBCL).Ten heavily treated patients with refractory DLBCL were given CBM.CD19 CAR-T cell(C-CAR011)treatment.The overall response rate was 20%and 50%at 4 and 12 weeks after the infusion of C-CAR011,respectively,and the disease control rate was 60%at 12 weeks after infusion.Treatment-emergent adverse events occurred in all patients.The incidence of cytokine release syndrome in all grades and grade^3 was 90%and 0,respectively,which is consistent with the safety profile of axicabtagene ciloleucel and tisagenlecleucel.Neurotoxicity or other dose-limiting toxicides was not observed in any dose cohort of C-CAR011 therapy.Antitumor efficacy was apparent across dose cohorts.Therefore,C-CAR011 is a safe and effective therapeutic option for Chinese patients with refractory DLBCL,and further large-scale clinical trials are warranted.

Prognostic factors and efficacy of GDP-R therapy in refractory/relapsed diffuse large B-cell lymphomas not eligible for high-dose therapy

Aim:The main aim of the present study was to evaluate the overall survival(OS)and time to treatment failure(TTF)in a cohort of relapsed/refractory diffuse large B-cell lymphomas(DLBCLs)not eligible for high-dose therapy(HDT)treated with gemcitabine in association with dexamethasone,cisplatin and rituximab(GDP-R)protocol.The secondary aim was to identify the prognostic factors impacting OS and TTF.Methods:The authors retrospectively analyzed 45 patients with refractory/relapsed DLBCLs treated with GDP-R.Results:Overall response rate(ORR)was 48.8%;complete response 15/45(33.3%),partial response 7/45(15.5%).Response was influenced by the number of previous therapies administered and International Prognostic Index(IPI)value.Although no significant impact occurred with regard to OS,patients pre-treated with 2 or<2 chemotherapeutic regimens had better ORR(P=0.014)and a longer TTF(P=0.029 in multivariate Cox model).IPI value also influenced TTF.Patients with<2 IPI value had significantly more prolonged TTF than the other ones(P=0.048 in multivariate Cox model).Treatment was well-tolerated,with the majority of patients treated on out-patient modality.GDP-R regimen represents a valid treatment for aggressive relapsed/refractory B-cell lymphoma not eligible for HDT thanks to its efficacy and good toxic profile.Conclusion:The number of previous chemotherapeutic regimens and IPI value select those who benefit more from this treatment.