Buɗewar ASH ta 2023 | Dr. Peihua Lu ta Gabatar da CAR-T don Binciken AML da ya Lalace/Rage Ragewa

Wani bincike na asibiti na mataki na farko game da CD7 CAR-T don R/R AML ta ƙungiyar Daopei Lu ya fara halarta a ASH

An gudanar da taron shekara-shekara na 65 na Ƙungiyar Nazarin Jini ta Amurka (ASH) ba tare da intanet ba (San Diego, Amurka) kuma a yanar gizo a ranakun 9-12 ga Disamba, 2023. Masananmu sun nuna wannan babban abin mamaki, inda suka ba da gudummawar sakamakon bincike sama da 60.

Sakamakon da aka samu kwanan nan na "Autologous CD7 CAR-T don cutar sankarar myeloid mai saurin dawowa/ragewa (R/R AML)", wanda Farfesa Peihua Lu na Asibitin Ludaopei da ke China ya bayar da rahoto a baki, ya sami kulawa sosai.

Maganin R/R AML yana haifar da matsala

R/R AML ba shi da kyakkyawan hasashen cutar, koda kuwa ana yi masa dashen ƙwayoyin halitta na allogeneic hematopoietic (allo-HSCT), kuma akwai buƙatar gaggawa ta asibiti don sabbin hanyoyin magani. A cewar Farfesa Peihua Lu, zaɓin da aka yi niyya yana da mahimmanci a cikin neman sabbin hanyoyin magani, kuma kusan kashi 30% na marasa lafiya na AML suna nuna CD7 a kan ƙwayoyin leukemoblasts da ƙwayoyin halittar da ke haifar da cutar.

A baya, Asibitin Lu Daopei ya ba da rahoton marasa lafiya 60 waɗanda suka yi amfani da CD7 CAR-T (NS7CAR-T) da aka zaɓa ta hanyar halitta don maganin cutar sankarar jini da lymphomas masu tsanani ta T-cell, wanda ke nuna inganci mai mahimmanci da kuma kyakkyawan yanayin aminci. An lura da aminci da ingancin faɗaɗa NS7CAR-T ga marasa lafiya da ke da R/R AML mai CD7-positive a cikin wani binciken asibiti na Mataki na I (NCT04938115) wanda aka zaɓa don wannan Taron Shekara-shekara na ASH.

Tsakanin watan Yunin 2021 da Janairun 2023, jimillar marasa lafiya 10 da ke dauke da R/R AML mai dauke da CD7-positive (CD7 expression >50%) sun shiga cikin binciken, tare da matsakaicin shekaru na shekaru 34 (shekaru 7 - shekaru 63). Matsakaicin nauyin ciwon daji na marasa lafiyar da aka yi wa rajista shine 17%, kuma majiyyaci daya ya nuna yana dauke da cutar extramedullary (EMD). Matsakaicin lokacin daga warewar tantanin halitta zuwa jiko na tantanin halitta na CAR-T shine kwanaki 15, kuma an ba da izinin yin maganin sauyi ga marasa lafiya da ke fama da cutar da ke tabarbarewa da sauri kafin a yi musu jiko. Duk marasa lafiya sun sami maganin fludarabine ta hanyar jijiya (30 mg/m2/d) da kuma maganin cyclophosphamide (300 mg/m2/d) na cire lymphatic chemotherapy na tsawon kwanaki uku a jere.

Fassarar Mai Bincike: Alfijir na Rage Zurfi

Kafin a yi rajista, an yi wa marasa lafiya matsakaicin magani na 8 (tsakanin: 3-17) a gaba. An yi wa marasa lafiya 7 dashen ƙwayoyin halitta na allogeneic hematopoietic stem cell dashen (allo-HSCT), kuma matsakaicin lokacin da ke tsakanin dashen da kuma komawa baya shine watanni 12.5 (watanni 3.5-19.5). Bayan jiko, matsakaicin kololuwar ƙwayoyin NS7CAR-T da ke yawo shine kwafi 2.72×105/μg (kwafi 0.671~5.41×105/μg) na DNA na genomic, wanda ya faru a kusan rana ta 21 (rana ta 14 zuwa rana ta 21) bisa ga q-PCR, da kuma a rana ta 17 (rana ta 11 zuwa rana ta 21) bisa ga FCM, wanda ya kasance 64.68% (40.08% zuwa 92.02%).

Mafi girman nauyin ciwon daji na marasa lafiya da aka yi wa binciken ya kusa kusan kashi 73%, kuma akwai ma wani lamari inda majiyyacin ya sami magunguna 17 a baya, in ji Farfesa Peihua Lu. Akalla marasa lafiya biyu da aka yi wa allurar allo-HSCT sun sake dawowa cikin watanni shida bayan dashen. A bayyane yake cewa maganin wadannan marasa lafiya yana cike da "wahala da cikas".

Bayanai masu ban sha'awa

Makonni huɗu bayan shigar ƙwayoyin NS7CAR-T, bakwai (70%) sun sami cikakkiyar gafara (CR) a cikin bargo, shida kuma sun sami CR mara kyau don cututtukan da suka rage a cikin ƙashi (MRD). Marasa lafiya uku ba su sami gafara ba (NR), tare da majiyyaci ɗaya da ke da EMD ya nuna gafarar wani ɓangare (PR) a ranar 35 ga kimantawar PET-CT, kuma an gano cewa duk marasa lafiya da ke da NR sun rasa CD7 a lokacin bin diddigin cutar.

Matsakaicin lokacin lura shine kwanaki 178 (kwanaki 28 - kwana 776). Daga cikin marasa lafiya bakwai da suka sami CR, marasa lafiya uku da suka sake kamuwa bayan dashen da suka gabata sun sami haɗin allo-HSCT na biyu kimanin watanni 2 bayan an yi musu magani ta hanyar amfani da ƙwayoyin NS7CAR-T, kuma wani majiyyaci ya kasance ba shi da cutar sankarar bargo a rana ta 401, yayin da marasa lafiya biyu da aka yi wa dashen na biyu suka mutu sakamakon dalilan da ba su sake kamuwa a rana ta 241 da 776; sauran marasa lafiya huɗu waɗanda ba su yi wa dashen ba, marasa lafiya 3 sun sake kamuwa a rana ta 47, 83, da 89, bi da bi (an gano asarar CD7 a cikin dukkan marasa lafiya uku), kuma majiyyaci 1 ya mutu sakamakon kamuwa da cutar huhu.

Dangane da aminci, yawancin marasa lafiya (80%) sun fuskanci ciwon sakin cytokine mai sauƙi (CRS) bayan an yi musu allurar, inda marasa lafiya na aji 7, aji 1 na II, da kuma marasa lafiya 2 (20%) suka fuskanci CRS na aji 3 na III. Babu wani mara lafiya da ya fuskanci cutar neurotoxicity, kuma 1 ya kamu da cutar da aka yi wa tiyatar cire fata daga jiki.

Wannan sakamakon ya nuna cewa NS7CAR-T na iya zama wata hanya mai kyau ta cimma nasarar farko ta CR ga marasa lafiya da ke dauke da R/R AML mai CD7, koda bayan an yi musu magani da dama a gaba. Kuma wannan tsari gaskiya ne ga marasa lafiya da ke fuskantar koma-baya bayan allo-HSCT tare da tsarin tsaro mai kyau.

Farfesa Lu ya ce, "Ta hanyar bayanan da muka samu a wannan karon, maganin CD7 CAR-T ga R/R AML yana da tasiri sosai kuma an jure shi sosai a farkon matakin, kuma yawancin marasa lafiya sun sami damar cimma CR da kuma gafara mai zurfi, wanda ba abu ne mai sauƙi ba. Kuma a cikin marasa lafiya na NR ko marasa lafiya da suka sake komawa baya, asarar CD7 ita ce babbar matsalar. Domin a tantance ingancin NS7CAR-T gaba ɗaya wajen magance AML mai CD7, babu shakka ana buƙatar a ƙara tabbatar da bin diddigin ta hanyar samun ƙarin bayanai daga yawan marasa lafiya da kuma tsawon lokacin bin diddigi, amma waɗannan kuma suna ba da bege da kwarin gwiwa ga asibitin."