2023 Pébruari: The results of the trial demonstrated that a novel terapi sél T reséptor antigen chimeric 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.
"Kami henteu pernah nyangka yén tingkat réspon bakal saluhur ieu," Matthew Frank, MD, PhD, asisten dosen kadokteran di division getih jeung cangkok sumsum jeung terapi sélular di Stanford University, ngawartoskeun Healio. "Éta mangrupikeun CAR-T anu épéktip sareng aman pikeun dipasihkeun ka pasien anu sakitu legana bakal ngagaduhan kabutuhan anu teu kacumponan."
kasang tukang
The CD22 protein on the surface of cancer cells is the tujuan 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 diarahkeun CAR-T nyababkeun laju réspon lengkep 70% diantara 58 pasien ngora anu kambuh atanapi refractory B-sél ALL anu geringna maju saatos CD19-diarahkeun CAR-T.
Frank nyatakeun, "Satengah pasien urang masih kambuh saatos nganggo CAR-T komérsial, sareng panyabab umum kambuh nyaéta downregulation atanapi ngahapus CD19." Urang diantisipasi réspon ku ngagunakeun antigen béda nu mucunghul ngajangjikeun pikeun barudak.
métodologi
Frank and coworkers tested their novel CD22-targeted CAR T-sél perlakuan 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 lymphoma whose disease progressed after prior CD19-directed CAR-T therapy or had CD19-negative disease.
Kabéh penderita iwal hiji anu dirawat salila sidang saméméhna geus narima CD19-diarahkeun Terapi sél T-mobil. Pamilon underwent lymphodepletion saméméh narima infusion tunggal sél CD22 CAR T dina dosage boh 1 106 sél / kg (n = 29) atawa 3 106 sél / kg (n = 9).
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).
papanggihan konci
36 people were diagnosed with sindrom sékrési sitokin. 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%).
Lima pasien (13%) ngagaduhan sindrom neurotoxicity pakait sareng sél éféktor imun. Salila sidang, teu aya kasus ICANS parna (kelas 3 atanapi langkung luhur) dilaporkeun.
Five patients, including three of the nine who received the larger dose, were diagnosed with CAR-associated lymphohistiocytosis hemophagocytic (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.
Panaliti mendakan PFS median 2.9 bulan (interval kapercayaan 95% [CI], 1.7 dugi ka henteu ngahontal) sareng OS median 22.5 bulan (95% CI, 8.3 dugi ka henteu ngahontal). Dina watesan PFS median (3 bulan vs. 2.6 bulan) jeung median OS, nu dosis handap tur luhur nunjukkeun efektivitas comparable (teu ngahontal vs 22.5 bulan).
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.
implikasi klinis
Nalika percobaan dimimitian dina 2018, sakedik kahartos naha sababaraha pasien CAR-T kambuh. Frank nyatakeun yén téori dasar, di luar biologi tumor, nyaéta kabugaran sél T anu goréng.
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 Mobil-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.
Uji coba multicenter fase 2 anu diusulkeun nganggo CD22 CAR-T bakal kalebet pasien anu ngagaduhan limfoma sél B ageung anu parantos kambuh saatos perlakuan sareng CAR-T anu diarahkeun CD19. Mangsa pendaptaran sigana bakal dimimitian usum panas ieu.
rujukans:
- Frank MJ, dkk. Abstrak 2. Dipidangkeun dina: Rapat Tandem | Rapat Transplantasi & Terapi Sélular ASTCT sareng CIBMTR, 15-19 Pebruari 2023; Orlando.
- Shah NN, et al. J Clin Oncol. 2020;doi:10.1200/JCO.19.03279.
