Otu prọfesọ mahadum Russia dị afọ iri asaa na ọkara na-arịa ọrịa multiple myeloma. Mgbe ọ natara ọgwụgwọ dị iche iche ma megharịa ya ugboro abụọ nke transplantation onwe ya, ọ mụtara maka ọgwụgwọ kachasị mma nke CAR-T na China, ya mere ọ bịara China ịnara ọgwụgwọ mkpụrụ ndụ CAR-T ma pụọ n'enweghị nsogbu mgbe ụbọchị iri na atọ nke infusion gasịrị. Na ndekọ nsochi kachasị ọhụrụ, dọkịta ahụla ọnọdụ mgbaghara zuru oke (CR) na nsonaazụ ule ya.
Ọgwụgwọ CAR-T, ma ọ bụ ọgwụgwọ mkpụrụ ndụ T-cell chimeric antigen receptor, bụ nnukwu ọganihu na ọgwụgwọ immunotherapy nkeonwe maka kansa. Usoro a gụnyere ịnakọta mkpụrụ ndụ T nke onye ọrịa, mgbe nke ahụ gasịrị, a na-eme mgbanwe injinịa mkpụrụ ndụ ihe nketa nke mkpụrụ ndụ T iji melite ikike mkpụrụ ndụ T iji mata ọrịa kansa kpọmkwem. A na-etinye mkpụrụ ndụ T ndị a gbanwere agbanwe (ya bụ, mkpụrụ ndụ CAR-T) n'ahụ onye ọrịa.
KQ-2003 bụ ngwaahịa BCMA/CD19 nke na-elekwasị anya na CAR T-cell abụọ, na-eji usoro CAR kachasị ọhụrụ eme ihe iji mee ka ọrụ na ntachi obi nke mkpụrụ ndụ dịkwuo mma, usoro CAR abụọ ahụ na-ebelatakwa mgbochi antigen nke ọgwụgwọ otu ebumnuche.
Ọmụmụ ihe a na-atụ anya ya na Investigator-Initiated (NCT04714827) na China na-achọ inyocha nchekwa, ndidi, na irè mbụ nke mkpụrụ ndụ CAR-T KQ-2003 n'ime ndị ọrịa (pts) nwere ọrịa myeloma relapse/refractory multiple myeloma (RRMM), ọkachasị ndị nwere ọrịa extramedullary (EMD).
Ụzọ
Nnwale a, nke nwere ọtụtụ etiti, nke mepere emepe, na-egosi ọnụọgụgụ RRMM nwere usoro ọgwụgwọ ≥1 gara aga gụnyere ọgwụ mgbochi proteasome (PI), na ọgwụ immunomodulatory (IMiDs), na/ma ọ bụ anti-CD38. Ndị Pts natara fludarabine (30 mg/m2/ụbọchị) na cyclophosphamide (300 mg/m2/ụbọchị) na ụbọchị -5 ruo -3, wee tinye otu mkpụrụ ndụ KQ-2003 CAR-T (ụbọchị 0) n'ime ọkwa dose atọ (DL) dabere na nhazi 3+3 ọkọlọtọ: DL1, DL2, ma ọ bụ DL3 (1.0, 2.0, ma ọ bụ 3.0 × 106 mkpụrụ ndụ CAR+/kg). Ebumnuche ya bụ inyocha nchekwa, ndidi, irè mbụ na njirimara PK/PD, yana ịchọpụta oke dose anabatara (MTD), oke nsị dose (DLT). A tụlere mmeghachi omume ọbara dịka ụkpụrụ IMWG na obere ọrịa fọdụrụ (MRD) si dị site na usoro ọgbọ ọhụrụ (NGF). A tụlere EMD dịka ụkpụrụ nzaghachi PET Refinement Response si dị.
Nsonaazụ
Dịka ọ dị na njedebe ọgwụgwọ nke Julaị 25, 2024, pasent 23 (52.2% nwoke; afọ etiti 64 (oke 52-77)) na RRMM natara KQ-2003 (3 DL1, 11 DL2 na 9 DL3). Oge nleba anya etiti bụ ọnwa 13.7 (oke 2.1-35.2). Ọnụọgụ ndị a natara ọnụọgụ ndị ọrịa ise gara aga (oke 2-11). 91.3% (21/23) bụ ndị na-anaghị anabata ọgwụ ugboro atọ, na pasent 26.1 (6/23) ndị na-anaghị anabata ọgwụ ugboro atọ. 65.2% (15/23) nwere profaịlụ cytogenetic dị elu/dị ize ndụ nke ukwuu.
Pasentị 60.9 (14/23) nke ndị nwere EMD na mmalite, gụnyere 7 extramedullary extraosseous (EM-E), 5 extramedullary-bone related (EM-B), 2 pts na ha abụọ.
N'ime otu EMD, pasent 5 (5/14, 35.7%) enweghị ihe ngosi a na-atụ anya ya na ọbara, PET-CT nyochakwara azịza ya.
Ọnụọgụ nzaghachi ọbara (ORR) bụ 100.0% (18/18), yana ọnụego sCR/CR nke 88.9% (16/18), ọnụego VGPR nke 11.1% (2/18). Oge etiti ruo nzaghachi mbụ bụ ọnwa 1.2 (N=18, oke 0.6–3.1; 22.2% ≤1.0 ọnwa), oge etiti ruo CR/sCR bụ ọnwa 2.7 (N=16, oke 0.6–9.1; 50.0% ≤3.0 ọnwa). N'ime akara 19 nke a na-enyocha maka MRD, 100% bụ MRD-negative (10-5), na ọnụego MRD-negative nke ọnwa 6 na ọnwa 12 bụ 80.0% (8/10) na 100.0% (3/3), n'otu n'otu.
PET ORR nke EMD pts bụ 85.7% (12/14), gụnyere 64.3% (9/14) mmeghachi omume metabolic zuru oke (CMR), 21.4% (3/14) mmeghachi omume metabolic nke akụkụ (PMR) na 14.3% (2/14) ọrịa metabolic kwụsiri ike (SMD). 64.3% (9/14) na 50.0% (7/14) nke EMD pts nwere > 50% na > 75% mbelata na nha nke plasmacytomas anụ ahụ dị nro, n'otu n'otu. Na pts 5 EMD na-enweghị ihe ngosi a na-atụ aro hematological, PET ORR bụ 80% (4/5) (2 CMR, 2 PMR na 1 SMD).
Erughị ogologo oge nzaghachi (DOR) (NR). Ọnụọgụ ndụ nke ọnwa isii na-enweghị ọganihu (PFS) na ọnụọgụ ndụ zuru oke (OS) bụ 86.5% (73.4–100) na 86.2% (72.8–100), ọnụego PFS na OS nke ọnwa 12 bụ 75.3% (58.4–97.0) na 86.2% (72.8–100) n'otu n'otu. PFS na OS nke etiti bụ NR.
N'ozuzu, mmadụ anọ nwụrụ, gụnyere mmadụ abụọ a mụrụ ma chọpụta na ha metụtara ọgwụgwọ (ma nke a bụ nnukwu oyi baa), na mmadụ abụọ nwụrụ maka ọrịa PD.
A hụrụ CRS na ICANS n'otu n'otu na 21/23 (91.3%, ọkwa 3/4 4.3%), na 5/23 (21.7%, ọkwa 3/4 8.7%). Oge etiti ruo mmalite CRS bụ 5d (oke 1–9) yana oge etiti nke 4d (oke 1–15). Oge etiti ruo mmalite ICANS bụ 10d (oke 8–23) yana oge etiti nke 3d (oke 1–9). Ahụghị DLT ọ bụla.
Nọmba mkpụrụ ndụ KQ-2003 CAR+ T (VCN) gosiri na Tmax nke etiti bụ 14.0, 11.5, na 9.0 d na DL1, DL2 na DL3, n'otu n'otu. Cmax nke etiti bụ 140.6, 168.2, na 83.9 copies/ug DNA nwere ogologo oge nke nnọgidesi ike. N'ime akara ndị nwere nleba anya ọnwa 6 na 12, 66.7% (10/15) na 62.5% (5/8) nwere mkpụrụ ndụ CAR+ T a na-achọpụta n'ọbara dị n'akụkụ.
Mmechi
BCMA/CD19 nke nwere CAR-T KQ-2003 nke na-elekwasị anya n'ụzọ abụọ gosiri nzaghachi mbụ, miri emi na nke siri ike na RRMM yana nchekwa a nabatara. Ihe kacha mkpa bụ na o nwere ike ịrụ ọrụ nke ọma na ọgwụgwọ EMD, gụnyere EM-E nke a na-apụghị ịgwọta, nke kwesịrị inyocha ọzọ.
Ugbu a, enwere ọtụtụ nnwale ụlọ ọgwụ CAR-T ndị ọzọ na China, ha na-achọkwa ndị ọrịa. Maka ndụmọdụ gbasara ọgwụ ọhụrụ na teknụzụ, ị nwere ike ịkpọtụrụ Ngalaba Mba Nile nke Ụlọ Ọgwụ Oncology nke Beijing South Region.
Nọmba ekwentị: 4008803716
Ozi ịntanetị:myimmnet@163.com
Ntụaka
1.http://en.novatim-zj.com/show-28-32-1.html
2.https://ash.confex.com/ash/2024/webprogram/Paper201160.html
3.http://myimm.net/mianyizhiliao/1939.html
Oge ozi: Nọvemba-26-2024