Ka Wehe ʻana o ASH 2023 | Hōʻike ʻo Kauka Peihua Lu iā CAR-T no ka Noiʻi AML Relapsed / Refractory

Ua hoʻomaka kahi haʻawina lapaʻau pae I o CD7 CAR-T no R/R AML e ka hui a Daopei Lu ma ASH.

Ua mālama ʻia ka Hālāwai Makahiki 65 o ka ʻAhahui ʻAmelika o Hematology (ASH) ma waho pūnaewele (San Diego, USA) a ma ka pūnaewele ma Dekemaba 9-12, 2023. Ua hōʻike nui kā mākou poʻe akamai i kēia ʻaha kūkā, me ka hāʻawi ʻana ma mua o 60 mau hopena noiʻi.

Ua loaʻa i nā hopena hou loa o "Autologous CD7 CAR-T no ka relapsed/refractory acute myeloid leukemia (R/R AML)", i hōʻike waha ʻia e Prof. Peihua Lu o ka Halemai ʻo Ludaopei ma Kina, ka nui o ka nānā ʻana.

ʻO ka mālama ʻana i ka R/R AML e hōʻike ana i kahi pilikia

He maikaʻi ʻole ka prognosis o R/R AML, ʻoiai ke hana ʻia nei ka allogeneic hematopoietic stem cell transplantation (allo-HSCT), a aia kahi pono lapaʻau wikiwiki no nā koho therapeutic hou. Wahi a Prof. Peihua Lu, he mea nui ke koho ʻana i ka pahuhopu i ka ʻimi ʻana i nā therapies hou, a ma kahi o 30% o nā maʻi AML e hōʻike i ka CD7 ma kā lākou leukemoblasts a me nā malignant progenitor cell.

Ma mua, ua hōʻike ka Halemai ʻo Lu Daopei i 60 mau maʻi i hoʻopili i ka CD7 CAR-T i koho kūlohelohe ʻia (NS7CAR-T) no ka mālama ʻana i nā leukemias a me nā lymphomas acute T-cell, e hōʻike ana i ka pono koʻikoʻi a me kahi ʻano palekana maikaʻi. Ua nānā ʻia a loiloi ʻia ka palekana a me ka pono o ka hoʻonui ʻana o NS7CAR-T i nā maʻi me ka CD7-positive R/R AML i loko o kahi noiʻi lapaʻau Phase I (NCT04938115) i koho ʻia no kēia Hālāwai Makahiki ASH.

Ma waena o Iune 2021 a me Ianuali 2023, ua kākau inoa ʻia he 10 mau maʻi me CD7-positive R/R AML (CD7 expression >50%) i loko o ke aʻo ʻana, me ka makahiki waena o 34 mau makahiki (7 mau makahiki - 63 mau makahiki). ʻO ka ukana tumor waena o nā maʻi i kākau inoa ʻia he 17%, a hoʻokahi maʻi i hōʻike ʻia me ka maʻi diffuse extramedullary (EMD). ʻO ka manawa waena mai ka hoʻokaʻawale ʻana o ke kelepona i ka hoʻokomo ʻana o ke kelepona CAR-T he 15 mau lā, a ua ʻae ʻia ka hoʻololi ʻana no nā maʻi me ka maʻi e hōʻino wikiwiki ana ma mua o ka lawelawe ʻia ʻana o ka infusion. Ua loaʻa i nā maʻi āpau ka intravenous fludarabine (30 mg/m2/d) a me ka cyclophosphamide (300 mg/m2/d) lymphatic removal chemotherapy no ʻekolu mau lā i hala.

Ka Wehewehe ʻana o ka Mea Noiʻi: ka wanaʻao o ka hoʻēmi hohonu

Ma mua o ke kākau inoa ʻana, ua loaʻa i nā maʻi ka awelika o 8 (pae: 3-17) mau lāʻau lapaʻau mua. Ua loaʻa i nā maʻi 7 ka hoʻoili ʻana o nā cell stem hematopoietic allogeneic (allo-HSCT), a ʻo ka manawa waena ma waena o ka hoʻoili ʻana a me ka hoʻi hou ʻana he 12.5 mau mahina (3.5-19.5 mau mahina). Ma hope o ka hoʻokomo ʻana, ʻo ka piko waena o nā cell NS7CAR-T e kahe ana he 2.72 × 105 kope / μg (0.671 ~ 5.41 × 105 kope / μg) o ka genomic DNA, i hana ʻia ma kahi o ka lā 21 (lā 14 a hiki i ka lā 21) e like me q-PCR, a ma ka lā 17 (lā 11 a hiki i ka lā 21) e like me FCM, ʻo ia hoʻi he 64.68% (40.08% a 92.02%).

ʻO ka ukana puʻupuʻu kiʻekiʻe loa o nā maʻi i kākau inoa ʻia i ke aʻo ʻana ua kokoke i 73%, a aia kekahi hihia kahi i loaʻa ai i ka mea maʻi he 17 mau lāʻau lapaʻau ma mua, wahi a Polopeka Peihua Lu. Ma ka liʻiliʻi he ʻelua o nā maʻi i hana ʻia i ka allo-HSCT i ʻike i ka hoʻi hou ʻana i loko o ʻeono mahina o ka hoʻoili ʻana. Ua maopopo he piha ka mālama ʻana i kēia mau maʻi i nā "pilikia a me nā keakea".

ʻIkepili hoʻohiki

ʻEhā pule ma hope o ka hoʻokomo ʻana o nā cell NS7CAR-T, ʻehiku (70%) i loaʻa ka hoʻomaha piha (CR) i loko o ka iwi iwi, a ʻeono i loaʻa ka CR maikaʻi ʻole no ka maʻi koena microscopic (MRD). ʻekolu mau maʻi i loaʻa ka hoʻomaha (NR), me hoʻokahi maʻi me EMD e hōʻike ana i kahi hoʻomaha hapa (PR) i ka lā 35 o ka loiloi PET-CT, a ua ʻike ʻia nā maʻi āpau me NR ua nalowale ka CD7 i ka wā o ka hahai ʻana.

ʻO ka manawa nānā waena he 178 mau lā (28 lā-776 mau lā). No nā maʻi ʻehiku i loaʻa iā CR, ʻekolu mau maʻi i hoʻi hou ma hope o ka hoʻoili mua ʻana i hana ʻia i ka consolidation second allo-HSCT ma kahi o 2 mau mahina ma hope o ka hoʻomaha ʻia e ka NS7CAR-T cell infusion, a ua ola kekahi maʻi me ka leukemia ʻole i ka lā 401, ʻoiai ʻelua mau maʻi transplant lua i make i nā kumu i hoʻi ʻole i ka hoʻi hou ʻana i nā lā 241 a me 776; ʻo nā maʻi ʻehā ʻē aʻe i hana ʻole i ka consolidation allo-HSCT, 3 mau maʻi i hoʻi hou i nā lā 47, 83, a me 89, (ua loaʻa ka nalowale o ka CD7 i nā maʻi ʻekolu), a ua make kekahi maʻi i ka maʻi pulmonary.

Ma ke ʻano o ka palekana, ʻo ka hapa nui o nā maʻi (80%) i loaʻa i ka cytokine release syndrome (CRS) ma hope o ka hoʻokomo ʻana, me 7 papa I, 1 papa II, a me 2 mau maʻi (20%) i loaʻa i ka papa III CRS. ʻaʻohe maʻi i loaʻa i ka neurotoxicity, a 1 i loaʻa i ka maʻi cutaneous graft-versus-host akahai.

Hōʻike kēia hopena he regimen hoʻohiki paha ʻo NS7CAR-T no ka hoʻokō ʻana i ka CR mua kūpono i nā poʻe maʻi me ka CD7-positive R/R AML, ʻoiai ma hope o ka hana ʻana i nā laina he nui o ka lāʻau lapaʻau ma mua. A he ʻoiaʻiʻo nō hoʻi kēia regimen i nā poʻe maʻi e ʻike ana i ka relapse ma hope o ka allo-HSCT me kahi ʻaoʻao palekana hiki ke hoʻokele ʻia.

Ua ʻōlelo ʻo Polopeka Lu, "Ma o ka ʻikepili i loaʻa iā mākou i kēia manawa, ua kūpono loa ka lāʻau CD7 CAR-T no R/R AML a ua ʻae maikaʻi ʻia i ka wā mua, a ua hiki i ka hapa nui o nā maʻi ke hoʻokō i ka CR a me ke kala hohonu, ʻaʻole maʻalahi. A i nā maʻi NR a i ʻole nā ​​maʻi i hoʻi hou i ka maʻi, ʻo ka nalowale o CD7 ka pilikia nui. I mea e loiloi piha ai i ka pono o NS7CAR-T i ka mālama ʻana i ka CD7-positive AML, pono e hōʻoia hou ʻia ka hahai ʻana ma o ka loaʻa ʻana o ka ʻikepili hou aku mai kahi heluna nui o nā maʻi a me ka manawa hahai lōʻihi, akā hāʻawi pū kēia i ka manaʻolana a me ka hilinaʻi i ke keʻena lapaʻau."