Kukadzi 2023: The results of the trial demonstrated that a novel chimeric antigen receptor T-cell therapy 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.
"Hatina kumbofunga kuti mitengo yekupindura ingakwira zvakanyanya," Matthew Frank, MD, PhD, mubatsiri purofesa wemishonga mukupatsanurwa kweropa uye marrow transplantation uye cellular therapy paStanford University, akaudza Healio. "CAR-T inoshanda chaizvo uye yakachengeteka kupa kuvarwere vanozonyanya kushaiwa."
kumashure
The CD22 protein on the surface of cancer cells is the chinangwa 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 yakatungamira CAR-T yakaguma ne70% yakakwana yekupindura mwero pakati pevarwere vadiki makumi mashanu nevasere vane kudzokazve kana kuramba B-cell VOSE vane hurwere hwakaenderera mberi zvichitevera CD58-yakatungamirwa CAR-T.
Frank akati, "Hafu yevarwere vedu vachiri kurwara mushure mekushandisa CAR-T yekutengeserana, uye chikonzero chakajairika chekudzokera kumashure kwaive kudzikiswa kana kubviswa kweCD19." Taitarisira mhinduro nekushandisa imwe antigen yairatidza kuva inovimbisa vechidiki.
Methodology
Frank and coworkers tested their novel CD22-targeted CAR T-sero kurapwa 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.
Varwere vese kunze kweumwe vakarapwa panguva yekutongwa vakambogamuchira CD19-yakanangana CAR T-cell kurapa. Vatori vechikamu vakaita lymphodepletion vasati vagamuchira imwe infusion yeCD22 CAR T masero pachiyero che 1 106 masero / kg (n = 29) kana 3 106 masero / 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).
Key dzakawanikwa
36 people were diagnosed with cytokine release syndrome. 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%).
Varwere vashanu (13%) vaive neurotoxicity syndrome yakabatana neaimmune effector masero. Munguva yekutongwa, hapana nyaya dzeICANS dzakakomba (giredhi 3 kana pamusoro) dzakataurwa.
Five patients, including three of the nine who received the larger dose, were diagnosed with CAR-associated hemophagocytic lymphohistiocytosis (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.
Vatsvakurudzi vakawana yepakati PFS yemwedzi 2.9 (95% nguva yekuvimba [CI], 1.7 kuti isati yasvika) uye yepakati OS yemwedzi 22.5 (95% CI, 8.3 kuti isati yasvika). Mukutaura kwepakati PFS (mwedzi 3 vs. 2.6 mwedzi) uye yepakati OS, iyo yakaderera uye yakakwirira doses yakaratidza kuenzaniswa kwekubudirira (isina kusvika vs. 22.5 mwedzi).
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.
Clinical zvinoreva
Sezvo kuyedza kwakatanga muna 2018, zvishoma zvakanzwisiswa nezve nei vamwe varwere veCAR-T vachidzokera. Frank akataura kuti dzidziso yakakosha, kunze kwebundu biology, yaive yakashata T-cell fitness.
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.
A proposed phase 2 multicenter trial uchishandisa CD22 CAR-T ichasanganisira varwere vane B-cell lymphoma hombe vakadzokera shure vachitevera kurapwa neCD19-inotungamirirwa neCAR-T. Nguva yekunyoresa ingangotanga zhizha rino.
References:
- Frank MJ, nevamwe. Abstract 2. Yakapiwa pa: Tandem Meetings | Transplantation & Cellular Therapy Misangano yeASTCT neCIBMTR, Kukadzi 15-19, 2023; Orlando.
- Shah NN, nevamwe. J Clin Oncol. 2020;doi:10.1200/JCO.19.03279.
