2023-fevral: The results of the trial demonstrated that a novel kimerik antigen retseptorlari T-hujayra terapiyasi elicited a response in adults with advanced large B-cell lymphoma who had relapsed following prior CAR-T.
According to statistics given during the Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, all but one of the 20 study patients who achieved an initial full response to therapy remained in remission as of the cutoff date.
"Javob darajasi bunchalik yuqori bo'ladi deb o'ylamagandik" Metyu Frank, MD, PhD, Stenford universitetining qon va ilik transplantatsiyasi va hujayra terapiyasi bo'limida tibbiyot professori yordamchisi, dedi Healio. "Bu asosan qondirilmagan ehtiyojga ega bo'lgan bemorlarga berish uchun juda samarali va xavfsiz CAR-T."
fon
The CD22 protein on the surface of cancer cells is the maqsad of an investigational autologous CAR T-cell treatment developed by Stanford University researchers. Using the CliniMACS Prodigy (Miltenyi Biotec) automated cell processing equipment, they produced the agent on-site over a 12-day period.
CD22 tomonidan yo'naltirilgan CAR-T, kasallik avvalgi CD70-yo'naltirilgan CAR-T dan keyin kuchaygan relapsli yoki refrakter B-hujayrali ALL bo'lgan 58 yosh bemorlarda 19% to'liq javob darajasiga olib keldi.
Frank shunday dedi: "Bemorlarimizning yarmi hali ham tijorat CAR-T-dan foydalangandan keyin ham qaytalanishdi va relapsning umumiy sababi CD19 ning tartibga solinishi yoki yo'q qilinishi edi." Biz yoshlar uchun istiqbolli bo'lgan boshqa antigen yordamida javoblarni kutdik.
Metodologiya
Frank and coworkers tested their novel CD22-targeted CAR T-hujayralarini davolash in a phase 1, single-institution, dose-escalation study.
The trial enrolled 38 persons (median age, 65 years; age range, 25-84; 55% men) with relapsed or refractory large B-cell limfoma whose disease progressed after prior CD19-directed CAR-T therapy or had CD19-negative disease.
Sinov davomida davolanganlardan tashqari barcha bemorlar CD19-ni qabul qilishgan CAR T-hujayra terapiyasi. Ishtirokchilar 22 1 hujayra/kg (n = 106) yoki 29 3 hujayra/kg (n = 106) dozasida CD9 CAR T hujayralarining bitta infuzionini olishdan oldin limfodepletsiyani boshdan kechirdilar.
The primary outcomes of this study were feasibility, safety, and the recommended phase 2 dose. Secondary objectives included overall response rate as determined by the investigator, duration of response, PFS, OS, and CAR-T-associated toxicity. At a cutoff date of December 27, 2022, the median follow-up period was 18.4 months (range: 1.5-38.6).
Asosiy topilmalar
36 people were diagnosed with sitokinlarni chiqarish sindromi. The only grade 3 adverse event occurred in the group receiving the highest dose. In the higher-dose group, grade 2 CRS occurred significantly more frequently (78% vs. 48%).
Besh bemorda (13%) immun effektli hujayralar bilan bog'liq neyrotoksiklik sindromi mavjud edi. Sud jarayonida og'ir ICANS (3 daraja yoki undan yuqori) holatlari haqida xabar berilmagan.
Five patients, including three of the nine who received the larger dose, were diagnosed with CAR-associated gemofagotsitik limfogistiyositoz (HLH), a hyperinflammatory response marked by significant hyperferritinemia and multiorgan failure.
The examination of efficacy revealed an ORR of 68% and a complete response rate of 53% for all patients treated. A complete response was achieved by fifteen patients (52%) who received the lower dose, and five individuals (56%) who received the larger dose.
Tadqiqotchilar o'rtacha PFSni 2.9 oy (95% ishonch oralig'i [CI], 1.7 - erishilmagan) va o'rtacha OS 22.5 oyni (95% CI, 8.3 - erishilmagan) aniqladilar. O'rtacha PFS (3 oyga nisbatan 2.6 oy) va o'rtacha OS nuqtai nazaridan, past va yuqori dozalar taqqoslanadigan samaradorlikni ko'rsatdi (22.5 oyga nisbatan erishilmadi).
As of the study’s end date, only one of twenty patients who had complete remission reported an illness return.
Researchers picked 1 106 cells/kg as the phase 2 dose recommendation because of its superior safety profile and comparable efficacy compared to the larger dose.
Klinik ta'siri
Tajriba 2018 yilda boshlangani sababli, ba'zi CAR-T bemorlari nima uchun qaytalanishi haqida kam narsa tushunilgan. Frankning ta'kidlashicha, asosiy nazariya, o'simta biologiyasidan tashqari, T-hujayralarining zaif fitnesidir.
Frank told Healio, “We’ve kind of blown that [thesis] out of the water because we’re taking the same autologous T cells from patients who have had a prior CAR-T and still getting a nearly 70% response rate and a 53% full response rate that appears to be quite durable.” This medication is quite promising, as it has a good response rate and a reasonable safety profile.
CD2 CAR-T dan foydalangan holda tavsiya etilgan 22-bosqich ko'p markazli sinov CD19-yo'naltirilgan CAR-T bilan davolashdan keyin qaytalangan yirik B-hujayrali limfomasi bo'lgan bemorlarni o'z ichiga oladi. Ro‘yxatga olish davri shu yozda boshlanadi.
ma'lumotnomas:
- Frank MJ va boshqalar. Annotatsiya 2. Taqdim etilgan: Tandem uchrashuvlari | ASTCT va CIBMTR ning transplantatsiya va uyali terapiya uchrashuvlari, 15 yil 19-2023 fevral; Orlando.
- Shah NN va boshqalar. J Clin Oncol. 2020;doi: 10.1200/JCO.19.03279.
