2023 Gufungura ASH | Muganga Peihua Lu Yerekana CAR-T kubushakashatsi bwisubiraho / Ubushakashatsi bwa AML

Icyiciro cya mbere cyubuvuzi bwa CD7 CAR-T kuri R / R AML nitsinda rya Daopei Lu ryatangiye muri ASH

Inama ngarukamwaka ya 65 y’umuryango w’abanyamerika w’ubuvuzi bw’indwara (ASH) yabereye ku murongo wa interineti (San Diego, muri Amerika) no ku rubuga rwa interineti ku ya 9-12 Ukuboza 2023. Intiti zacu zerekanye igitaramo gikomeye muri iyi nama, zitanga ibisubizo birenga 60 by’ubushakashatsi.

Ibisubizo biheruka bya "Autologous CD7 CAR-T kubisubiramo / bivuguruza acute myeloid leukemia (R / R AML)", byavuzwe na Prof. Peihua Lu wo mu bitaro bya Ludaopei mu Bushinwa, byitabiriwe cyane.

Kuvura R / R AML birerekana ikibazo

R / R. uburyo bushya bwo kuvura, hamwe n’abarwayi bagera kuri 30% ba AML bagaragaza CD7 kuri leukemoblasts na selile progenitor selile.

Mbere, ibitaro bya Lu Daopei byatangaje abarwayi 60 basabye CD7 CAR-T yatoranijwe bisanzwe (NS7CAR-T) kugira ngo bavure T-selile acute leukemiya na lymphoma, bagaragaza imikorere ikomeye n’umutekano mwiza. Umutekano n’ingirakamaro bya NS7CAR-T kwaguka ku barwayi bafite CD7-nziza R / R AML byagaragaye kandi bisuzumwa mu bushakashatsi bw’ubuvuzi bwo mu cyiciro cya mbere (NCT04938115) bwatoranijwe muri iyi nama ngarukamwaka ya ASH.

Hagati ya Kamena 2021 na Mutarama 2023, abarwayi 10 bose bafite CD7-nziza ya R / R AML (imvugo ya CD7> 50%) bariyandikishije muri ubwo bushakashatsi, bafite hagati y’imyaka 34 (7 ans - 63 ans) Ikibyimba cyo hagati umutwaro w'abarwayi biyandikishije wari 17%, kandi umurwayi umwe yerekanye indwara ya diffuse extramedullary (EMD). time Igihe giciriritse kuva mu bwigunge kugeza selile CAR-T cyari iminsi 15, kandi kuvura inzibacyuho byari byemewe ku barwayi bafite indwara zangirika vuba mbere. infusion yatanzwe.Abarwayi bose bakiriye fludarabine yo mu mitsi (30 mg / m2 / d) na cyclophosphamide (300 mg / m2 / d) ya lymphatic ikuraho chimiotherapie muminsi itatu ikurikiranye.

Ibisobanuro by'abashakashatsi: Umuseke wo Kugabanuka Byimbitse

Mbere yo kwiyandikisha, abarwayi babazwe hagati ya 8 (intera: 3-17). Abarwayi 7 bari baratewe insimburangingo ya allogeneic hematopoietic stem selile (allo-HSCT), naho intera yo hagati yo guhindurwa no kwisubiraho yari amezi 12.5 (amezi 3.5-19.5) .Nyuma yo gushiramo, impuzandengo yo hagati ya selile NS7CAR-T yari 2.72 × 105 kopi / μg (0.671 ~ 5.41 × 105 kopi / μg) ya ADN ya genomic, yabaye nko ku munsi wa 21 (umunsi wa 14 kugeza ku wa 21) ukurikije q-PCR, no ku munsi wa 17 (umunsi wa 11 kugeza ku wa 21) ukurikije FCM , yari 64,68% (40.08% kugeza kuri 92.02%).

Prof. Peihua Lu yavuze ko umutwaro w’ibibyimba byinshi by’abarwayi biyandikishije muri ubwo bushakashatsi wari hafi 73%, ndetse hari n’aho umurwayi yari amaze kwivuza 17 mbere. Nibura babiri mu barwayi batewe allo-HSCT bahuye n’ibibazo mu mezi atandatu nyuma yo guterwa. Biragaragara ko kuvura aba barwayi byuzuye "ingorane n'inzitizi".

Amakuru atanga icyizere

Nyuma y'ibyumweru bine nyuma ya NS7CAR-T yinjizwamo selile, barindwi (70%) bagezeho neza (CR) mumitsi yamagufa, naho batandatu bagera kuri CR mbi kuburwayi bwa microscopique (MRD). abarwayi batatu ntibageze ku gukira (NR), umurwayi umwe urwaye EMD agaragaza ko yakiriye igice (PR) ku munsi wa 35 PET-CT, kandi abarwayi bose bafite NR basanze bafite CD7 babikurikiranye.

Igihe cyo kwitegereza hagati cyari iminsi 178 (iminsi 28-iminsi 776). Mu barwayi barindwi bageze kuri CR, abarwayi batatu bari basubiye inyuma nyuma yo guhindurwa mbere bongeye guhuzwa allo-HSCT ya kabiri nyuma y'amezi 2 nyuma yo gukira indwara ya NS7CAR-T, kandi umurwayi umwe yagumye adafite indwara ya leukemia ku munsi wa 401, mu gihe babiri ba kabiri- abarwayi ba transplant bapfuye bazize kudasubira kumunsi 241 na 776; abandi barwayi bane batigeze bahura na HSCT, abarwayi 3 basubiye ku minsi 47, 83, na 89 (igihombo cya CD7 cyabonetse ku barwayi uko ari batatu), naho umurwayi 1 yapfuye azize indwara zifata ibihaha.

Ku bijyanye n'umutekano, umubare munini w'abarwayi (80%) bahuye na syndrome ya cytokine yoroheje (CRS) nyuma yo gushiramo, hamwe n'icyiciro cya 7 I, icyiciro cya II, n'abarwayi 2 (20%) bafite uburambe bwa III CRS. nta barwayi bahuye na neurotoxicity, kandi 1 barwaye indwara yoroheje ya graft-na-host-host.

Igisubizo cyerekana ko NS7CAR-T ishobora kuba gahunda itanga icyizere cyo kugera kuri CR yambere kubarwayi bafite CD7-nziza ya R / R AML, ndetse na nyuma yo gukorerwa imirongo myinshi yubuvuzi imbere. Kandi ubu buryo nukuri kubarwayi bahura nibibazo nyuma ya allo-HSCT hamwe numwirondoro wumutekano ucungwa.

Prof. Lu yagize ati: "Binyuze mu makuru twabonye muri iki gihe, kuvura CD7 CAR-T kuri R / R AML ni byiza kandi byihanganirwa hakiri kare, kandi umubare munini w'abarwayi washoboye kugera kuri CR no gukira cyane. , ntibyoroshye. Kandi mu barwayi ba NR cyangwa abarwayi bongeye kugaruka, igihombo cya CD7 nicyo kibazo nyamukuru. mu kubona amakuru menshi ku baturage benshi barwayi kandi igihe kinini cyo kuyakurikirana, ariko kandi ibyo bitanga ibyiringiro byinshi n'icyizere ku ivuriro. "