Imininingwane eningiliziwe:
Lolu ucwaningo lwesikhungo esisodwa, olungalo olulodwa, olunelebula evulekile. Ngemva kokuhlangabezana nemibandela yokufaneleka nokubhalisa ocwaningweni, iziguli zizobhekana ne-leukapheresis ukuze kuqoqwe ama-autologous lymphocyte. Uma amaseli enziwe, iziguli zizobe seziqhubekela ku-lymphodepleting chemotherapy nge-cyclophosphamide kanye ne-fludarabine izinsuku ezingu-1-2 ezilandelanayo okulandelwa ukumnika kwamaseli e-CAR T ngethamo elihlosiwe lamaseli angu-3-10×105/kg.
Imigomo
Imigomo Yokufaka:
- I-CD19-positive i-non-Hodgkin lymphoma confirmed by cytology or histology according to WHO2016 criteria:
- Diffuse large B-cell lymphoma: including unspecified (DLBCL, NOS), chronic inflammation-related DLBCL, primary cutaneous DLBCL (leg type), EBV-positive DLBCL (NOS); and high-grade B-cell lymphoma (including high-grade B-cell lymphoma, NOS, and high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements); and primary mediastinal large B-cell lymphoma; and T-cell-rich histiocytosis B-cell lymphoma; and transformed DLBCL (such as follicular lymphoma, chronic lymphocytic leukemia/small B-lymphocytic lymphoma transformed DLBCL); patients with the above isisu types have been treated with at least first- and second-line drugs and have stable disease for ≤12 months , or when the best Disease progression after efficacy; or disease progression or relapse after autologous stem cell transplantation ≤12 months;
- According to WHO2016 criteria cytology or histology confirmed CD19 positive: follicular cell i-lymphoma. Patients with this tumor type have received at least third-line therapy, and recurrence or disease progression has occurred within 2 years after third-line therapy or more. Currently in disease progression, stable disease, or partial remission;
- According to WHO2016 standard cytology or histology confirmed CD19 positive: i-mantle cell lymphoma. Such patients have not been cured or relapsed after at least three-line treatment and are not suitable for stem cell transplantation or relapse after stem cell transplantation;
- Ubudala ≥iminyaka engu-18 (kufaka phakathi umkhawulo);
- Ngokwenguqulo ka-2014 yenqubo ye-Lugano, kukhona okungenani isilonda esingakaleka esinezinhlangothi ezimbili njengesisekelo sokuhlola: izilonda ze-intranodal, zichazwa ngokuthi: ububanzi obude> 1.5cm; ngezilonda ze-extranodal, ububanzi obude kufanele bube>>1.0cm;
- Isilinganiso somsebenzi weqembu le-Eastern Cooperative Oncology Isikolo se-ECOG 0-2;
- Ukufinyelela kwe-venous okudingekayo ukuze kuqoqwe kungasungulwa, futhi kukhona amaseli anele aqoqwe yi-apheresis engahlanganisiwe yokukhiqizwa kwamaseli e-CAR-T;
- Ukusebenza kwesibindi nezinso, umsebenzi we-cardiopulmonary uhlangabezana nalezi zidingo ezilandelayo:
- I-serum creatinine≤2.0×ULN;
- Ingxenye ye-ventricular ejection yesokunxele ≥ 50% futhi akukho ukukhishwa kwe-pericardial okusobala, akukho ECG engavamile;
- Ukugcwala komoyampilo wegazi ≥92% esimweni esingenawo umoya-mpilo;
- Isamba segazi se-bilirubin≤2.0×ULN (ngaphandle kokubaluleka komtholampilo);
- I-ALT ne-AST≤3.0×ULN (enokungena kwesimila sesibindi≤5.0×ULN);
- Ukwazi ukuqonda futhi usayine ngokuzithandela imvume enolwazi.
Imigomo Yokukhishwa:
- Uthole ukwelashwa kwe-CAR-T noma okunye ukwelashwa kweseli okushintshiwe ngofuzo ngaphambi kokuhlolwa;
- Uthole ukwelashwa kwe-anti-tumor (ngaphandle kokuvimbela i-systemic immune checkpoint noma i-stimulation therapy) phakathi kwamaviki angu-2 noma i-5 half-life (noma yikuphi okufushane) ngaphambi kokuhlolwa. I-3-half-life iyadingeka ukuze ubhalise (isb, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 receptor agonist, 4-1BB receptor agonist, njll.);
- Labo abaye bathola i-hematopoietic stem cell transplantation (ASCT) phakathi kwamasonto angu-12 ngaphambi kwe-apheresis, noma abaye bathola i-allogeneic hematopoietic stem cell transplantation (HSCT), noma labo abanokufakelwa kwesitho esiqinile; i-immunosuppression iyadingeka phakathi kwamaviki ama-2 ngaphambi kwe-apheresis yeBanga lesi-2 nangaphezulu kwe-GVHD yomuthi;
- Iziguli ezinokubandakanyeka kwe-atrial noma i-ventricular lymphoma noma zidinga ukwelashwa okuphuthumayo ngenxa yesisindo se-tumor njengokuvinjelwa kwamathumbu noma ukucindezelwa kwe-vascular;
- Ugonywe ngomjovo wokugomela bukhoma emasontweni ayisi-6 ngaphambi kokuqeda uchoko;
- Ingozi ye-Cerebrovascular noma isithuthwane senzeke phakathi nezinyanga ezingu-6 ngaphambi kokusayina i-ICF;
- Umlando we-myocardial infarction, i-cardiac bypass noma i-stent, i-angina engazinzile noma esinye isifo senhliziyo esibalulekile emtholampilo phakathi nezinyanga ezingu-12 ngaphambi kokusayina i-ICF;
- Izifo ezizimele ezisebenzayo noma ezingalawulwa (njenge-Crohn's disease, i-rheumatoid arthritis, i-systemic lupus erythematosus), ngaphandle kwalezo ezingadingi ukwelashwa kwesistimu;
- Malignant tumors other than non-Hodgkin lymphoma within 5 years prior to screening, except for adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, Ductal carcinoma in situ;
- Ukutheleleka okungalawuleki phakathi kweviki elingu-1 ngaphambi kokuhlolwa;
- I-Hepatitis B surface antigen (HBsAg) noma i-hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) Ukutholwa kwe-DNA titer kukhulu kunobubanzi obujwayelekile bereferensi; noma i-hepatitis C virus (HCV) i-antibody positive and peripheral blood C I-Hepatitis virus (HCV) Ukuhlolwa kwe-RNA titer kukhulu kunobubanzi obujwayelekile bereferensi; noma i-human immunodeficiency virus (HIV) antibody positive; noma ukuhlolwa kogcunsula; ukuhlolwa kwe-cytomegalovirus (CMV) DNA;
- Abesifazane abakhulelwe noma abancelisayo; noma abesifazane abaneminyaka yobudala yokuzala abahlolwe ukuthi bakhulelwe ngesikhathi sokuhlolwa; noma iziguli zesilisa noma zesifazane ezingazimisele ukusebenzisa ukuvimbela inzalo kusukela ngesikhathi sokusayina ifomu lemvume unolwazi kuya onyakeni ongu-1 ngemva kokuthola ukujova iseli le-CAR-T;
- Abanye abaphenyi bakubona kungafanele ukubamba iqhaza ocwaningweni.
