Gufungura ASH mu 2023 | Dr. Peihua Lu atanga CAR-T ku bushakashatsi bwa AML bwo gusubira inyuma / bwo kutumvikana

Inyigo y'icyiciro cya mbere ku ndwara ya CD7 CAR-T kuri R/R AML yakozwe n'ikipe ya Daopei Lu itangira muri ASH

Inama ngarukamwaka ya 65 y’Umuryango w’Abanyamerika w’Ubuvuzi bw’Amazi (ASH) yabereye kuri interineti (San Diego, muri Amerika) ku ya 9-12 Ukuboza 2023. Intiti zacu zagaragaje iyi nama neza, zitanga umusaruro w’ubushakashatsi urenga 60.

Ibisubizo biheruka bya "Autologous CD7 CAR-T ku ndwara ya leukemia ya myeloid isubira inyuma/isubira inyuma (R/R AML)", byatangajwe mu magambo na Porofeseri Peihua Lu wo mu bitaro bya Ludaopei mu Bushinwa, byakunzwe cyane.

Uburyo bwo kuvura R/R AML butera ikibazo gikomeye

R/R AML ifite imiterere mibi, ndetse no mu gihe iterwa allogeneic hematopoietic hematopoietic stem cells (allo-HSCT), kandi hari hakenewe byihutirwa uburyo bushya bwo kuvura. Nk’uko Porofeseri Peihua Lu abivuga, guhitamo intego ni ingenzi mu gushaka uburyo bushya bwo kuvura, kandi hafi 30% by’abarwayi ba AML bagaragaza CD7 ku turemangingo twabo twa leukemoblasts n’uturemangingo twa kanseri.

Mbere yaho, Ibitaro bya Lu Daopei byagaragaje abarwayi 60 bashyizeho CD7 CAR-T (NS7CAR-T) yatoranijwe mu buryo bw’umwimerere mu kuvura kanseri y’amaraso ya T-cell leukemia na lymphomas, bigaragaza ko ifite akamaro gakomeye kandi ko ifite umutekano mwiza. Umutekano n’ubushobozi bwo kwaguka kwa NS7CAR-T ku barwayi bafite CD7-positive R/R AML byagaragaye kandi bisuzumwa mu bushakashatsi bwakozwe mu cyiciro cya mbere (NCT04938115) bwatoranijwe muri iyi nama ngarukamwaka ya ASH.

Hagati ya Kamena 2021 na Mutarama 2023, abarwayi 10 bose hamwe bafite CD7-positive R/R AML (igaragara rya CD7 >50%) biyandikishije muri ubu bushakashatsi, bafite imyaka ibarirwa muri za 34 (imyaka 7 - imyaka 63) Umubare w’ibibyimba by’abarwayi biyandikishije wari 17%, naho umurwayi umwe agaragaraho indwara iterwa n’ingirabuzimafatizo (EMD). Igihe cyo hagati kuva ku kwitandukanya kw’uturemangingo kugeza ku guterwa kwa CAR-T ni iminsi 15, kandi ubuvuzi bw’impinduka bwaremerewe abarwayi bafite indwara zigenda zirushaho kuba mbi mbere yo guterwa. Abarwayi bose bahawe imiti ya fludarabine (30 mg/m2/umunsi) na cyclophosphamide (300 mg/m2/d) yo gukuramo imiti ya lymphatic mu mitsi mu minsi itatu yikurikiranya.

Ubusobanuro bw'Umushakashatsi: Umwanya wo Guhangana mu Buryo Bukomeye

Mbere yo kwiyandikisha, abarwayi bakorewe ubuvuzi bw’ibanze inshuro 8 (kuva ku munsi wa 3 kugeza kuri 17). Abarwayi 7 bari barakorewe ubuvuzi bw’ibanze bwa allogeneic hematopoietic hematopoietic (allo-HSCT), kandi igihe cyo hagati yo guterwa no kongera gusubira inyuma cyari amezi 12.5 (amezi 3.5-19.5). Nyuma yo guterwa, igipimo cy’igipimo cy’uturemangingo twa NS7CAR-T cyari kopi 2.72 × 105 / μg (kopi 0.671 ~ 5.41 × 105 / μg) bya ADN ya genomic, byabaye hafi ku munsi wa 21 (umunsi wa 14 kugeza ku munsi wa 21) hakurikijwe q-PCR, no ku munsi wa 17 (umunsi wa 11 kugeza ku munsi wa 21) hakurikijwe FCM, byari 64.68% (40.08% kugeza 92.02%).

Umubare munini w’ibibyimba by’abarwayi biyandikishije muri ubu bushakashatsi wari hafi 73%, ndetse hari n’aho umurwayi yari yarahawe ubuvuzi 17 bwabanje, nk’uko byatangajwe na Porofeseri Peihua Lu. Nibura babiri mu barwayi bakorewe allo-HSCT basubiye kurwara mu mezi atandatu nyuma yo guterwa ubwoko bw’ibibyimba. Biragaragara ko ubuvuzi bw’aba barwayi bwuzuyemo "ingorane n’imbogamizi".

Amakuru ashimishije

Nyuma y'ibyumweru bine nyuma yo guterwa selile za NS7CAR-T, barindwi (70%) babonye koroherwa burundu (CR) mu musemburo w'amagufwa, naho batandatu babonye ko CR nta ndwara isanzwe igaragara (MRD). Abarwayi batatu ntibabonye koroherwa (NR), umurwayi umwe ufite EMD yagaragaje koroherwa igice (PR) ku munsi wa 35 w'isuzuma rya PET-CT, kandi abarwayi bose bafite NR basanze bafite ikibazo cya CD7 mu gihe cyo gukurikirana.

Igihe cyo kwitegereza cyari iminsi 178 (iminsi 28 kugeza ku minsi 776). Mu barwayi barindwi bahuye na CR, abarwayi batatu bari barasubiye kwandura nyuma yo guterwa ubwandu bwa mbere bakorewe consolidation ya kabiri ya allo-HSCT amezi abiri nyuma yo koroherwa no guterwa selile za NS7CAR-T, naho umurwayi umwe agumana kanseri y'amaraso akiri muzima ku munsi wa 401, mu gihe abarwayi babiri batewe ubwa kabiri bapfuye bazize indwara zitasubira kwandura ku munsi wa 241 na 776; abandi barwayi bane batakorewe consolidation ya allo-HSCT, abarwayi 3 bongeye kwandura ku munsi wa 47, 83, na 89, uko bikurikirana (hagaragaye igihombo cya CD7 ku barwayi bose uko ari batatu), naho umurwayi umwe yapfuye azize indwara z'ibihaha.

Ku bijyanye n'umutekano, abarwayi benshi (80%) bahuye n'indwara yo gusohora cytokine (CRS) nyuma yo guterwa, abarwayi bo mu cyiciro cya mbere cya 7, abo mu cyiciro cya kabiri cya 1, n'abarwayi 2 (20%) bahuye n'indwara yo gutwika mu bwonko yo mu cyiciro cya gatatu. Nta barwayi bahuye n'indwara yo mu bwonko, naho umwe muri bo yarwaye indwara yo gukurura mu ruhu iterwa n'udukoko two mu bwoko bwa graft-versus-host.

Ibi bisubizo bigaragaza ko NS7CAR-T ishobora kuba uburyo bwiza bwo kugera ku barwayi bafite CD7-positive R/R AML, ndetse no nyuma yo kuvurwa inshuro nyinshi mbere. Kandi ubu buryo ni ukuri no ku barwayi basubira inyuma nyuma yo gufata imiti ya allo-HSCT bafite umutekano uhagije.

Porofeseri Lu yagize ati: "Binyuze mu makuru twabonye kuri iyi nshuro, uburyo bwo kuvura CD7 CAR-T kuri R/R AML burakora neza kandi bwihanganirwa mu ntangiriro, kandi abarwayi benshi bashoboye kugera kuri CR no kugabanya ububabare, ibyo bikaba bitaboroheye. Kandi ku barwayi ba NR cyangwa abarwayi basubiye mu buzima, kubura CD7 ni cyo kibazo nyamukuru. Kugira ngo hasuzumwe neza akamaro ka NS7CAR-T mu kuvura CD7-positive AML, nta gushidikanya ko gukurikirana bigomba kwemezwa kurushaho binyuze mu kubona amakuru menshi aturutse ku barwayi benshi no gukurikirana igihe kirekire, ariko ibi binatanga icyizere n'icyizere ku ivuriro."