Febhuwari 2023: The results of the trial demonstrated that a novel i-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.
"Asikaze sicabange ukuthi amanani okuphendula azoba phezulu kanjena," Matthew Frank, MD, PhD, umsizi kaprofesa wezokwelapha ekuhlukaniseni igazi nomnkantsha kanye nokwelashwa kwamaselula eStanford University, utshele uHealio. “Isebenza kahle kakhulu futhi iphephile i-CAR-T ukunikeza iziguli ezizoba nesidingo esingahlangatshezwanga.”
Background
The CD22 protein on the surface of cancer cells is the umgomo 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.
I-CD22 iqondise i-CAR-T iholele esilinganisweni sokuphendula esiphelele esingama-70% phakathi kweziguli ezisencane ezingama-58 ezine-B-cell ebuyelwe kabusha noma ehlanekezelwe BONKE okugula kwazo kwaqhubekela phambili kulandela i-CAR-T eqondiswe ku-CD19 ngaphambili.
UFrank uthe, “Ingxenye yeziguli zethu isabuyelwa wumqemane ngemva kokusebenzisa i-CAR-T yokuhweba, futhi imbangela evamile yokuphindela emuva kwaba ukwehliswa noma ukususwa kwe-CD19.” Besilindele izimpendulo ngokusebenzisa i-antigen ehlukile ebonakale ithembisa intsha.
Indlela yokusebenzisa
Frank and coworkers tested their novel CD22-targeted Ukwelashwa kwe-CAR T-cell 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 i-lymphoma whose disease progressed after prior CD19-directed CAR-T therapy or had CD19-negative disease.
Zonke iziguli ngaphandle kweyodwa ezelashwa ngesikhathi socwaningo ngaphambili zazithole i-CD19-directed Ukwelashwa kwe-CAR T-cell. Abahlanganyeli bathole i-lymphodepletion ngaphambi kokuthola ukumnika okukodwa kwamaseli e-CD22 CAR T ngesilinganiso se-1 106 cells/kg (n = 29) noma 3 106 cells/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).
Ukuthola okusemqoka
36 people were diagnosed with i-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%).
Iziguli ezinhlanu (13%) zazine-neurotoxicity syndrome ehambisana namaseli e-immune effector. Ngesikhathi sokuqulwa kwecala, awekho amacala e-ICANS anzima (ibanga lesi-3 noma ngaphezulu) abikiwe.
Five patients, including three of the nine who received the larger dose, were diagnosed with CAR-associated i-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.
Abacwaningi bathole i-PFS emaphakathi yezinyanga ezingu-2.9 (isikhawu sokuzethemba esingu-95% [CI], 1.7 esingafinyelelwanga) kanye ne-OS emaphakathi yezinyanga ezingu-22.5 (95% CI, 8.3 ukuze ingafinyelelwanga). Ngokuya nge-PFS emaphakathi (izinyanga ezi-3 vs. 2.6 izinyanga) kanye ne-OS emaphakathi, imithamo ephansi nephezulu ibonise ukusebenza kahle okuqhathaniswayo (akufinyelelwanga uma kuqhathaniswa nezinyanga ezingama-22.5).
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.
Izinkinga zomtholampilo
Njengoba ucwaningo luqala ngo-2018, kuncane okwaqondwa ngokuthi kungani ezinye iziguli ze-CAR-T ziphindela emuva. UFrank wathi inkolelo-mbono eyisisekelo, ngaphandle kwe-tumor biology, kwakuwukufaneleka kwe-T-cell okungalungile.
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.
Uhlolo oluhlongozwayo lwesigaba sesi-2 lwe-multicenter kusetshenziswa i-CD22 CAR-T luzofaka iziguli ezine-B-cell lymphoma enkulu ezibuye zabuyela emuva ngemva kokwelashwa nge-CD19-directed CAR-T. Isikhathi sokubhalisa cishe sizoqala kuleli hlobo.
Izikhombos:
- UFrank MJ, et al. Abstract 2. Yethulwa kokuthi: Tandem Meetings | I-Transplantation & Cellular Therapy Meetings ye-ASTCT ne-CIBMTR, Feb. 15-19, 2023; Orlando.
- Shah NN, et al. J Clin Oncol. 2020;doi:10.1200/JCO.19.03279.
