Febraayo 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.
"Weligay uma malaynayn in heerka jawaabtu ay sidan u sarayso," Matthew Frank, MD, PhD, kaaliyaha borofisar ku takhasusay dawada ee qaybinta dhiiga iyo beerista dhuuxa iyo daawaynta gacanta ee Jaamicadda Stanford, ayaa u sheegay Healio. "Waa CAR-T aad waxtar u leh oo ammaan ah in la siiyo bukaannada kuwaas oo inta badan yeelan doona baahi aan la daboolin."
Background
The CD22 protein on the surface of cancer cells is the bartilmaameed 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 ee la hago CAR-T waxay keentay 70% jawaab celin dhammays tiran oo ka mid ah 58 bukaan oo da'yar oo soo noqnoqday ama dib u celinaya DHAMMAAN kuwaas oo jirkooda uu sii socday ka dib markii hore ee CD19-ku hagaysay CAR-T.
Frank wuxuu yiri, "Badh ka mid ah bukaannadayada ayaa weli soo noqday ka dib markii ay isticmaaleen CAR-T ganacsi, iyo sababta caadiga ah ee soo noqoshada waxay ahayd hoos u dhigista ama tirtirka CD19." Waxaan filaynay jawaabaha anagoo adeegsanayna antigen-ka duwan oo u muuqday mid rajo u leh dhalinyarada.
Mabaadi'da
Frank and coworkers tested their novel CD22-targeted CAR T-cell daawaynta 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 qanjiro whose disease progressed after prior CD19-directed CAR-T therapy or had CD19-negative disease.
Dhammaan bukaannada marka laga reebo mid la daweeyay intii lagu jiray tijaabada ayaa hore u helay CD19-ku-tilmaamay CAR T-cell daaweynta. Ka qaybqaatayaasha ayaa la maray lymphodepletion ka hor inta aan la helin hal faleebo oo ah unugyada CD22 CAR T oo ah qiyaasta 1 106 unug/kg (n = 29) ama 3 106 unug/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).
Natiijooyinka muhiimka ah
36 people were diagnosed with cytokine sii daayo 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%).
Shan bukaan (13%) ayaa lahaa xanuunka neurotoxicity ee la xidhiidha unugyada difaaca jirka. Intii ay socotay tijaabada, lama soo sheegin kiisas ICANS daran (fasalka 3 ama ka sareeya).
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.
Cilmi-baarayaashu waxay heleen dhexdhexaadiyaha PFS ee bilaha 2.9 (95% isku-kalsoonida [CI], 1.7 oo aan la gaarin) iyo OS dhexdhexaad ah bilaha 22.5 (95% CI, 8.3 oo aan la gaarin). Marka la eego dhexdhexaadinta PFS (3 bilood vs. 2.6 bilood) iyo OS dhexdhexaadka ah, qiyaasaha hoose iyo kuwa sare waxay muujiyeen waxtar la mid ah (aan la gaadhin 22.5 bilood).
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.
Saameynta caafimaadka
Sida tijaabadu bilaabatay 2018, wax yar ayaa laga fahmay sababta bukaannada CAR-T qaarkood ay u soo noqdaan. Frank waxa uu sheegay in aragtida aasaasiga ah, ee ka baxsan bayoolajiyada burada, ay ahayd fayaqabka unugyada T-unuga oo liita.
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.
Tijaabo la soo jeediyay oo ah wajiga 2 oo la isticmaalayo CD22 CAR-T waxaa ku jiri doona bukaanada qaba lymphoma weyn ee B-cell kuwaas oo dib u soo noqday ka dib daawaynta CD19-ku haga CAR-T. Muddada isdiiwaangelinta waxay u badan tahay inay bilaabanto xagaagan.
Tixraacas:
- Frank MJ, iyo al. Abstract 2. Lagu Soo Bandhigay: Kulamada Tandem | Ku-tallaalidda & Kulamada Daaweynta Gacanta ee ASTCT iyo CIBMTR, Febraayo 15-19, 2023; Orlando.
- Shah NN, iyo al. J Clin Oncol. 2020;doi:10.1200/JCO.19.03279.
