2023 ASH Wehe | Hāʻawi ʻo Kauka Peihua Lu i ka CAR-T no ka noiʻi ʻana i ka AML Relapsed / Refractory

ʻO kahi haʻawina hoʻomaʻamaʻa pae I o CD7 CAR-T no R/R AML e ka hui o Daopei Lu i hoʻomaka ma ASH

ʻO ka 65th Annual Meeting of the American Society of Hematology (ASH) i mālama ʻia ma waho (San Diego, USA) a ma ka pūnaewele ma Dekemaba 9-12, 2023. Ua hōʻike maikaʻi kā mākou mau loea i kēia ʻaha kūkā, hāʻawi ʻoi aku ma mua o 60 mau hopena noiʻi.

ʻO nā hualoaʻa hou loa o "Autologous CD7 CAR-T for relapsed/refractory acute myeloid leukemia (R/R AML)", i haʻi waha ʻia e Prof. Peihua Lu o ka Halemai Ludaopei ma Kina, ua loaʻa ka manaʻo nui.

ʻO ka mālama ʻana i ka R/R AML he pilikia

ʻAʻole maikaʻi ka wānana o R/R AML, ʻoiai i ka wā e hele ana i ka allogeneic hematopoietic stem cell transplantation (allo-HSCT), a aia kahi koi wikiwiki no nā koho therapeutic novel. Wahi a Prof. nā lāʻau lapaʻau hou, a ma kahi o 30% o ka poʻe maʻi AML e hōʻike i ka CD7 ma kā lākou leukemoblasts a me nā pūnaewele progenitor malignant.

Ma mua, ua hōʻike ka Halemai Lu Daopei i nā maʻi 60 i hoʻohana i ka CD7 CAR-T (NS7CAR-T) i koho maoli ʻia no ka mālama ʻana i nā maʻi leukemias a me nā lymphomas T-cell, e hōʻike ana i ka pono nui a me kahi profile palekana maikaʻi. ʻO ka palekana a me ka pono o NS7CAR-T ʻO ka hoʻonuiʻana i nā maʻi me ka CD7-positive R / R AML ua nānāʻia a loiloiʻia i loko o ka Phase I clinical study (NCT04938115) i kohoʻia no kēia ASH Annual Meeting.

Ma waena o Iune 2021 a me Ianuali 2023, he 10 mau mea maʻi me CD7-positive R/R AML (CD7 expression>50%) i kākau inoa ʻia i ke aʻo ʻana, me ka makahiki waena o 34 mau makahiki (7 mau makahiki - 63 mau makahiki) ʻO ka ukana o ka poʻe maʻi i kākau inoa ʻia he 17%, a hoʻokahi mea maʻi i hōʻike ʻia me ka maʻi diffuse extramedullary (EMD). Ua lawelawe ʻia ka infusion. Loaʻa nā maʻi āpau i ka fludarabine intravenous (30 mg / m2 / d) a me ka cyclophosphamide (300 mg / m2 / d) lymphatic removal chemotherapy no ʻekolu mau lā.

ʻO ka wehewehe ʻana o ka mea noiʻi: the Dawn of Deep Mitigation

Ma mua o ke kākau inoa ʻana, ua loaʻa nā mea maʻi i ka median o 8 (range: 3-17) nā lāʻau lapaʻau mua. Ua loaʻa i nā maʻi 7 ka allogeneic hematopoietic stem cell transplantation (allo-HSCT), a ʻo ka manawa waena ma waena o ka transplantation a me ka hoʻi hou ʻana he 12.5 mahina (3.5-19.5 mau mahina) .Ma hope o ka infusion, ʻo ka median peak o ka circulating NS7CAR-T cell he 2.72 × 105. kope / μg (0.671 ~ 5.41 × 105 kope / μg) o genomic DNA, i loaʻa 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 , he 64.68% (40.08% a 92.02%).

Ua kokoke i ka 73% ka haawe koko kiekie loa o na ma'i i kakauia, a he hookahi wale no hihia i loaa i ka mea ma'i he 17 mau lapaau mua, wahi a Prof. Peihua Lu. Ma kahi o ʻelua mau maʻi i loaʻa i ka allo-HSCT i loaʻa hou i loko o ʻeono mahina o ka hoʻololi ʻana. Ua maopopo ka piha o ka mālama ʻana i kēia mau maʻi i nā "pilikia a me nā pilikia".

ʻIke hoʻohiki

ʻEhā pule ma hope o ka NS7CAR-T cell infusion, ʻehiku (70%) i loaʻa i ke kala piha (CR) i loko o ka iwi iwi, a ʻeono i loaʻa i ka CR maikaʻi ʻole no ka microscopic residual maʻi (MRD). ʻekolu mau maʻi i loaʻa ʻole i ke kala ʻana (NR), me hoʻokahi mea maʻi me EMD e hōʻike ana i kahi kala kala (PR) ma ka lā 35 PET-CT loiloi, a ʻo nā mea maʻi āpau me NR ua loaʻa iā CD7 nalowale i ka hahai ʻana.

ʻO ka manawa nānā ma waena o 178 mau lā (28 lā-776 lā). ʻO nā maʻi ʻehiku i loaʻa i ka CR, ʻekolu mau maʻi i hoʻi hou ma hope o ka transplantation mua i hoʻohui ʻia i ka lua allo-HSCT ma kahi o 2 mau mahina ma hope o ke kala ʻia ʻana e ka NS7CAR-T cell infusion, a hoʻokahi mea maʻi i noho ola ʻole i ka maʻi leukemia i ka lā 401, ʻoiai ʻelua mau lua- Ua make nā maʻi transplant no nā kumu hoʻihoʻi ʻole i nā lā 241 a me 776; ʻO nā maʻi ʻehā ʻē aʻe i loaʻa ʻole i ka consolidation allo- HSCT, 3 mau maʻi i hoʻi hou i nā lā 47, 83, a me 89, i kēlā me kēia (ua loaʻa ka CD7 i loko o nā maʻi āpau ʻekolu), a ua make ka maʻi 1 i ka maʻi pulmonary.

Ma ke ʻano o ka palekana, ʻike ka hapa nui o nā maʻi (80%) i ka maʻi maʻi cytokine release (CRS) ma hope o ka infusion, me 7 papa I, 1 papa II, a me 2 mau maʻi (20%) i ʻike i ka papa III CRS. ʻaʻohe poʻe maʻi i ʻike i ka neurotoxicity, a ua hoʻomohala ʻo 1 i ka maʻi graft-versus-host maʻi.

Hōʻike kēia hopena i ka NS7CAR-T he regimen hoʻohiki no ka hoʻokō ʻana i ka CR mua maikaʻi i nā maʻi me CD7-positive R/R AML, ʻoiai ma hope o ke kau ʻana i nā laina he nui o ka lāʻau lapaʻau i mua. A he ʻoiaʻiʻo nō hoʻi kēia regimen i nā poʻe maʻi i ʻike i ka hoʻihoʻi hou ʻana ma hope o allo-HSCT me kahi ʻaoʻao palekana hiki ke mālama.

Ua ʻōlelo ʻo Prof. Lu, "Ma o ka ʻikepili i loaʻa iā mākou i kēia manawa, ʻoi aku ka maikaʻi o ka mālama ʻana i ka CD7 CAR-T no R/R AML a ʻae maikaʻi ʻia i ka wā mua, a ʻo ka hapa nui o nā mea maʻi i hiki ke hoʻokō i ka CR a me ke kala hohonu. , ʻaʻole maʻalahi i nā maʻi NR a i ʻole nā ​​​​maʻi i hoʻihoʻi ʻia, ʻo ka lilo ʻana 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 hoʻopaʻa ʻia ka hahai ʻana. ma ka loaʻa ʻana o nā ʻikepili hou aʻe mai ka nui o ka poʻe maʻi a me ka lōʻihi o ka hahai ʻana, akā hāʻawi kēia i ka manaʻolana a me ka hilinaʻi nui i ke keʻena. "