Fabrairu 2023: The results of the trial demonstrated that a novel chimeric antigen receptor T-cell far 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.
"Ba mu taɓa tunanin adadin martanin zai kai haka ba," Matthew Frank, MD, PhD, Mataimakin farfesa a fannin likitanci a cikin rarrabawar jini da dashen bargo da kuma salon salula a Jami'ar Stanford, ya shaida wa Healio. "Yana da matukar tasiri kuma mai aminci CAR-T don ba marasa lafiya waɗanda galibi suna da buƙatun da ba a biya su ba."
Tarihi
The CD22 protein on the surface of cancer cells is the manufa 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 da aka ba da umarnin CAR-T ya haifar da ƙimar amsawa ta kashi 70 cikin 58 a tsakanin ƙananan marasa lafiya 19 da suka koma ko tantanin halitta B-cell ALL waɗanda rashin lafiyarsu ta ci gaba biyo bayan CDXNUMX-directed CAR-T.
Frank ya ce, "Rabin marasa lafiyarmu har yanzu sun sake komawa bayan sun yi amfani da CAR-T na kasuwanci, kuma abin da ya haifar da koma baya shine raguwa ko share CD19." Mun yi tsammanin mayar da martani ta hanyar amfani da antigen daban wanda ya bayyana alƙawarin ga matasa.
Hanyoyi
Frank and coworkers tested their novel CD22-targeted CAR T-cell magani 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 linzoma whose disease progressed after prior CD19-directed CAR-T therapy or had CD19-negative disease.
Duk marasa lafiya banda wanda aka yi wa magani a lokacin gwaji sun riga sun karɓi CD19-directed CAR T-cell far. Mahalarta sun sha lymphodepletion kafin su karbi jiko guda ɗaya na CD22 CAR T Kwayoyin a kashi na ko dai 1 106 cell / kg (n = 29) ko 3 106 cell / 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).
Abun binciken
36 people were diagnosed with cytokine saki ciwo. 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%).
Marasa lafiya biyar (13%) suna da ciwon neurotoxicity da ke da alaƙa da sel masu tasiri na rigakafi. A yayin gwajin, ba a sami rahoton wani lamari na ICANS mai tsanani (aji na 3 ko sama) ba.
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.
Masu bincike sun sami matsakaicin PFS na watanni 2.9 (95% tazarar amincewa [CI], 1.7 don ba a kai ba) da kuma OS na tsakiyar watanni 22.5 (95% CI, 8.3 ba a kai ba). Dangane da PFS na tsakiya (watanni 3 vs. 2.6 watanni) da kuma OS na tsakiya, ƙananan ƙananan allurai da mafi girma sun nuna tasiri mai kama (ba a kai vs. 22.5 months).
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.
Abubuwan magunguna
Kamar yadda gwajin ya fara a cikin 2018, an ɗan fahimci dalilin da yasa wasu marasa lafiyar CAR-T ke komawa. Frank ya bayyana cewa ainihin ka'idar, a waje da ilimin halittar jiki, rashin lafiyar T-cell ne.
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.
Gwajin multicenter na lokaci 2 da aka tsara ta amfani da CD22 CAR-T zai haɗa da marasa lafiya tare da babban lymphoma na B-cell waɗanda suka sake komawa bayan jiyya tare da CD19-directed CAR-T. Da alama lokacin yin rajista zai fara wannan bazara.
references:
- Frank MJ, et al. Abstract 2. An Gabatar da shi a: Taron Tandem | Dasawa & Taro na Farfadowa na ASTCT da CIBMTR, Fabrairu 15-19, 2023; Orlando.
- Shah NN, et al. J Clin Oncol. 2020; doi:10.1200/JCO.19.03279.
