2023 ASH Budewa | Dokta Peihua Lu Yana Gabatar da CAR-T don Binciken AML Mai Rushewa / Refractory

Nazarin asibiti na kashi na na CD7 CAR-T don R/R AML ta ƙungiyar Daopei Lu ta fara halarta a ASH

An gudanar da taron shekara-shekara karo na 65 na Ƙungiyar Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrun Ƙwararrunmu sun ba da gudummawar fiye da 60 sakamakon bincike.

Sakamakon karshe na "Autologous CD7 CAR-T don sake dawowa/mai saurin kamuwa da cutar sankarar jini ta myeloid (R/R AML)", wanda farfesa Peihua Lu na asibitin Ludaopei da ke kasar Sin ya ruwaito a baki, ya samu kulawa sosai.

Jiyya na R/R AML yana ba da matsala

R / R AML yana da rashin fahimta mara kyau, ko da lokacin da ake jurewa allogeneic hematopoietic stem cell transplantation (allo-HSCT), kuma akwai buƙatar gaggawa na asibiti don zaɓuɓɓukan hanyoyin warkewa na zamani. A cewar Farfesa Peihua Lu, zaɓin manufa yana da mahimmanci a cikin nema don neman magani. sababbin hanyoyin kwantar da hankali, kuma game da 30% na marasa lafiya na AML suna bayyana CD7 akan leukemoblasts da ƙwayoyin zuriyarsu.

A baya can, asibitin Lu Daopei ya ba da rahoton marasa lafiya 60 da suka yi amfani da CD7 CAR-T (NS7CAR-T) da aka zaɓa ta halitta don maganin cutar sankarar jini mai tsanani da lymphomas na T-cell, yana nuna tasiri mai mahimmanci da ingantaccen bayanin aminci. Amintaccen da ingancin NS7CAR-T fadada cikin marasa lafiya tare da CD7-tabbatacce R / R AML an lura kuma an kimanta su a cikin binciken asibiti na Phase I (NCT04938115) wanda aka zaɓa don wannan taron shekara-shekara na ASH.

Tsakanin Yuni 2021 da Janairu 2023, jimlar marasa lafiya 10 tare da CD7-tabbatacce R/R AML (CD7 magana> 50%) sun shiga cikin binciken, tare da matsakaicin shekaru 34 shekaru (7 shekaru - 63 shekaru) Ciwon daji na tsakiya nauyin marasa lafiya da aka yi rajista ya kasance 17%, kuma mai haƙuri ɗaya ya gabatar da cutar da ke yaduwa (EMD). An yi amfani da jiko. Duk marasa lafiya sun karbi fludarabine na ciki (30 mg / m2 / d) da cyclophosphamide (300 mg / m2 / d) cirewar ƙwayar lymphatic chemotherapy na kwanaki uku a jere.

Fassarar Mai Bincike: Alfijir na Rage Zurfi

Kafin yin rajista, marasa lafiya sun sami matsakaicin matsakaici na 8 (kewaye: 3-17) hanyoyin kwantar da hankali na gaba. 7 marasa lafiya sun yi amfani da allogeneic hematopoietic stem cell transplantation (allo-HSCT), kuma tsaka-tsakin tsaka-tsakin lokaci tsakanin dasawa da sake dawowa shine watanni 12.5 (watanni 3.5-19.5) . Bayan jiko, matsakaicin matsakaicin matsakaici na NS7CAR-T sel ya kasance 2.72 × 105. kwafi / μg (0.671 ~ 5.41 × 105 kwafi / μg) na DNA na genomic, wanda ya faru a kusan ranar 21 (ranar 14 zuwa ranar 21) bisa ga q-PCR, kuma a ranar 17 (ranar 11 zuwa ranar 21) bisa ga FCM , wanda ya kasance 64.68% ( 40.08% zuwa 92.02%).

Mafi girman nauyin ƙari na marasa lafiya da aka yi rajista a cikin binciken ya kusan kusan kashi 73%, kuma akwai ma wani lamari da majiyyaci ya karɓi jiyya 17 a baya, in ji Farfesa Peihua Lu. Aƙalla biyu daga cikin marasa lafiya waɗanda suka sami allo-HSCT sun sake dawowa cikin watanni shida na dasawa. A bayyane yake cewa maganin wadannan marasa lafiya yana cike da "matsala da cikas".

Bayanan alƙawari

Makonni hudu bayan jiko tantanin halitta na NS7CAR-T, bakwai (70%) sun sami cikakkiyar gafara (CR) a cikin kasusuwan kasusuwa, kuma shida sun sami CR korau don cututtukan da suka rage (MRD). marasa lafiya guda uku ba su sami gafara ba (NR), tare da mai haƙuri guda ɗaya tare da EMD yana nuna raguwar ɓarna (PR) a ranar 35 PET-CT kimantawa, kuma duk marasa lafiya tare da NR sun sami asarar CD7 a biyo baya.

Tsakanin lokacin lura shine kwanaki 178 (kwanaki 28-776). Daga cikin marasa lafiya bakwai da suka sami CR, marasa lafiya uku waɗanda suka sake dawowa bayan dasawa da suka gabata sun sami ƙarfafawa na biyu allo-HSCT kamar watanni 2 bayan gafara ta hanyar jiko tantanin halitta na NS7CAR-T, kuma mai haƙuri ɗaya ya kasance ba tare da cutar sankarar bargo ba a ranar 401, yayin da biyu na biyu- marasa lafiya da aka dasa sun mutu sakamakon rashin dawowa a ranakun 241 da 776; Sauran marasa lafiya huɗu waɗanda ba su sami haɗin gwiwa ba-HSCT, marasa lafiya 3 sun sake dawowa a ranakun 47, 83, da 89, bi da bi (an sami asarar CD7 a cikin duka marasa lafiya uku), kuma mai haƙuri 1 ya mutu daga kamuwa da cutar huhu.

Dangane da aminci, yawancin marasa lafiya (80%) sun sami ciwo mai sauƙi na cytokine saki (CRS) bayan jiko, tare da 7 grade I, 1 grade II, da 2 marasa lafiya (20%) sun sami digiri na III CRS. babu marasa lafiya da suka sami neurotoxicity, kuma 1 sun sami rauni mai laushi na fata-da-mai masaukin baki.

Wannan sakamakon yana nuna cewa NS7CAR-T na iya zama tsari mai ban sha'awa don samun ingantaccen CR na farko a cikin marasa lafiya tare da CD7-tabbatacce R/R AML, ko da bayan yin layukan jiyya da yawa a gaba. Kuma wannan tsarin kuma gaskiya ne a cikin marasa lafiya waɗanda suka sami koma baya bayan allo-HSCT tare da bayanin martabar aminci mai sarrafawa.

Farfesa Lu ya ce, "Ta hanyar bayanan da muka samu a wannan lokacin, maganin CD7 CAR-T na R/R AML yana da tasiri sosai kuma an jure shi sosai a farkon matakin, kuma yawancin marasa lafiya sun sami damar samun CR da zurfin gafara. , wanda ba shi da sauƙi kuma a cikin marasa lafiya na NR ko marasa lafiya da suka sake dawowa, asarar CD7 ita ce babbar matsala don tantance ingancin NS7CAR-T a cikin maganin CD7-tabbatacce AML. ta hanyar samun ƙarin bayanai daga yawan masu haƙuri da kuma tsawon lokacin bin diddigin, amma waɗannan kuma suna ba da fata mai yawa da kwarin gwiwa ga asibitin."