NgoFebhuwariry 2023, uhlolo lwesigaba 1 esikhungweni esisodwa sathola ukuthi kuphephile futhi kungenzeka ukuthi abantu abane-B-cell lymphoma (LBCL) enkulu efakwe ngaphambili (LBCL) basebenzise i-CD22-directed chimeric antigen receptor (CAR) T-cell therapy ngemva kokuphinda ku-CD19. -qondiswe Ukwelashwa kwe-CAR T-cell. Ukwengeza, iziguli zibonise amazinga aphezulu okuphendula jikelele (ORRs), futhi izimpendulo eziphelele (CRs) kulezi ziguli zitholakale ziqinile.
Isethulo somlobi ocwaningayo oholayo u-Matthew J. Frank, MD, PhD, umsizi kaprofesa wezokwelapha e-Division of Bone Marrow Transplant & Cellular Therapy e-Stanford Cancer Institute, wathi, "Ukujobelela okukodwa kwe-CAR22 kukhiqize amazinga aphezulu okusabela ekuphathweni kakhulu ngaphambi kwesikhathi. iziguli ezinkulu ze-B-cell lymphoma eziphinde zabuyela emuva ngemva kwe-CAR19.” UFrank ungumqondisi wocwaningo kanye nomsizi kaprofesa wezokwelapha.
CD19-directed Ukwelashwa kwe-CAR T-cell has led to significant responses in patients with relapsed/refractory LBCL; however, if relapse occurs, patients have a very poor prognosis, and many exhibit CD19 loss or reduced expression.
UFrank wathi, “Kunokuntuleka kwezindlela zokwelapha ezinikezwa ngemva kokugula okungapheli.” Njengoba kunikezwe ukubikezelwa okubi kweziguli ezibuyela emuva ngemva kokuthola imithi yokwelapha i-carnitine, kunesidingo esiphuthumayo esingafinyeleleki semithi yokwelapha emisha.
CD22 is of interest as a target for CAR T-cell therapy as it can be found on the surface of malignant B cells in 95% of B-cell acute lymphoblastic leukaemias (ALLs) and LBCLs. CD22-directed CAR T-cell therapy has already demonstrated high response rates in patients with heavily pretreated ALL.
Adults with B-cell ALL and B-cell i-non-Hodgkin lymphoma were enrolled in the dose-escalation phase 1 study of CAR T-cell therapy directed at CD22. Frank presented at the Tandem Meetings the results of the LBCL cohort.
All patients in the cohort had relapsed/refractory LBCL, including diffuse LBCL not otherwise specified, transformed follicular lymphoma, marginal zone lymphoma, i-lymphocytic leukemia engapheli/small lymphocytic lymphoma, primary mediastinal B-cell lymphoma, and secondary central nervous system involvement. In addition, patients were resistant to CD19-directed CAR T-cell therapy or had CD19-negative disease in conjunction with any CD22 expression. Patients who had previously received CAR T-cell therapy had to have at least 30 days passed since their last infusion and less than 5% CAR-positive cells in their peripheral blood, according to flow cytometry.
Iziguli zithole u-1 x 106 (umthamo wezinga 1) noma u-3 x 106 (umthamo wezinga 2) womuthi ohlosiwe we-CD22 (izinga lomthamo 2). Ngaphambi kokujova, iziguli zithole i-fludarabine emithanjeni (30 mg/m2) ne-cyclophosphamide (500 mg) ukuze zinikeze i-lymphodepleting chemotherapy.
Izinjongo eziyinhloko zocwaningo kwakuwukuba nokwenzeka kokukhiqiza, izincomo zomthamo wesigaba 2, ukuphepha, kanye nobuthi. I-ORR ehlolwe umphenyi, ubude besikhathi sokuphendula, ukusinda kwe-progression-free (PFS), ukusinda okuphelele (OS), ubuthi obuhlobene ne-CAR T, i-CD22 antigen expression, amazinga eseli e-CAR-positive egazini, kanye nephrofayili ye-serum cytokine kwakuyiziphetho zesibili.
Ezigulini ezibhalisiwe ze-41, umkhiqizo we-CAR T-cell wenziwa ngempumelelo kuma-38 (95%), njengoba i-2 yayinamaseli e-T anganele we-leukapheresis. Isilinganiso sesikhathi esiphakathi kwe-leukapheresis kanye ne-infusion sasiyizinsuku eziyi-18.
The median age of participants who received CAR T-cell therapy was 65 (range, 25-84), they had an ECOG performance status of 0 or 1, and they had received a median of 4 prior lines of therapy (range, 3-8). 74% of patients had diffuse LBCL, and 21% had transformed follicular i-lymphoma. 39% of patients were diagnosed with non-germinal centre B-cell-like disease, and 18% had double-hit status. 97% of patients had previously received CD19-directed CAR T-cell therapy, and 18% had previously undergone autologous hematopoietic stem cell transplantation. 29 percent of patients did not achieve a CR to any prior therapy.
Isikhathi sokulandelela esimaphakathi kuzo zonke iziguli kwakuyizinyanga ezingu-18.4 (ububanzi: 1.5-38.6), ngaleso sikhathi i-ORR yayingu-68% futhi izinga le-CR lalingu-53%. I-PFS emaphakathi kwakuyizinyanga ezingu-2.9 (isikhawu sokuzithemba esingu-95% [CI], 1.7-NR) futhi i-OS emaphakathi kwakuyizinyanga ezingu-22.5 (95% CI, 8.3-NR).
Ezingeni le-dose 1 (n = 29), iziguli zalandelwa isikhathi esimaphakathi sezinyanga ezingu-14.1 (uhla, 1.5-38.6), okubonisa i-66% ORR kanye ne-52% CR rate. Ukusinda kwe-Median-free progress-free kwakuyizinyanga ezingu-3.0 (95% CI, 1.6-NR) kanye nokusinda okuphelele okumaphakathi kube yi-NR (95% CI, 8.3-NR).
Ezingeni le-dose 2 (n = 9), ukulandelwa okumaphakathi kwakuyizinyanga ezingu-27.1 (ububanzi: 24.7-33.5), i-ORR yayingu-78%, futhi izinga le-CR lalingu-55%. I-PFS emaphakathi kwakuyizinyanga ezingu-2.6 (isikhawu sokuzithemba esingu-95%: 1.3-NR) futhi i-OS emaphakathi yayiyizinyanga ezingu-22.5 (isikhawu sokuzithemba esingu-95%: 5.5-NR).
Isiguli esisodwa kuphela kwezingu-1 esithole i-CR esibuye sabuyela esimweni sokunqanyulwa kwedatha, okubonisa ukuthi ama-CR ahlala isikhathi eside. Ngenyanga yesithathu, zonke iziguli ezazithuthuke ekwelashweni zase zenze kanjalo.
In 95% of patients, i-cytokine release syndrome was observed, with grade 1 events occurring in 37%, grade 2 in 55%, and grade 3 in 3%. 8% of patients experienced neurologic events of grade 1 severity, while 5% experienced events of grade 2 severity. 18% of patients also reported toxicity resembling i-hemophagocytic lymphohistiocytosis.
Isiguli esisodwa esisezingeni le-dose 2 sabulawa yi-sepsis ngosuku lwama-40, futhi isiguli esisodwa saba ne-myelodysplasia ehlobene nokwelashwa/i-acute myeloid leukemia ngaphandle kobufakazi bokuthi i-LBCL iphinde yalulama ezinyangeni eziyi-11 ngemuva kokuthola ukwelashwa okuqondiswe ku-CD22.
Izinga lethamo elinconyiwe lesigaba 2 linqunywe ukuthi lingu-1.
Ulwazi olushicilelwe ngaphambilini lwaluchaza kabanzi ukwelashwa kweziguli ezintathu zokuqala.
Zonke iziguli ezimbili zazinezici ezinobungozi obukhulu futhi zithole okungenani imigqa yokwelashwa emihlanu yangaphambili, okuhlanganisa nokwelashwa kwe-CAR T-cell eqondiswe ku-CD19. Phambilini esinye seziguli sake sathola imishanguzo emibili ye-CAR T-cell, eyesibili eyayihloselwe i-CD19 ne-CD20. Zontathu iziguli zithole i-CR, isiguli esi-3 sathola i-CR ngosuku lwama-28. Ama-CR agcinwe iminyaka engaphezu kwemithathu.
UFrank ubuye waphawula ukuthi "ukusabalala kwe-CAR22 kukhulu ngokuphindwe kashumi futhi kuphikelela kune-CAR19."
Ukuze ufunde kabanzi mayelana neziguli eseziphinde zabuyela emuva ngemva kokwelashwa kwe-CAR T-cell eqondiswe ku-CD19, uvivinyo oluhleliwe lwesigaba sesi-2 lwale agent luyasungulwa. Icala lizoqala kuleli hlobo.
Okubhekwayo
1. Frank MJ, Sahaf B, Baird J, et al. CD22 CAR T cell therapy induces durable remissions in patients with large B cell lymphoma who relapse after CD19 CAR T cell therapy. Presented at: 2023 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL. Abstract 2.
2. Baird JH, Frank MJ, Craig J, et al. Ukwelashwa kwe-CAR T-cell eqondiswa nge-CD22 kudala ukukhululwa okuphelele ku-CD19 eqondiswe ku-CAR-refractory enkulu ye-B-cell lymphoma. Igazi. 2021;137(17):2321-2325. doi:10.1182/blood.2020009432
