Bishii Febraayory 2023, a phase 1 trial at a single institution found that it was safe and possible for people with heavily pretreated large B-cell lymphoma (LBCL) to use CD22-directed chimeric antigen receptor (CAR) T-cell therapy after relapse on CD19-directed CAR T-cell daaweynta. In addition, patients exhibited high overall response rates (ORRs), and complete responses (CRs) in these patients were found to be durable.
A presentation by lead study author Matthew J. Frank, MD, PhD, assistant professor of medicine in the Division of Bone Marrow Transplant & Cellular Therapy at the Stanford Cancer Institute, said, “A single infusion of CAR22 produced high response rates in heavily pretreated large B-cell lymphoma patients who relapsed after CAR19.” Frank is the director of the study and an assistant professor of medicine.
CD19-directed CAR T-cell daaweynta 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.
Frank waxa uu yidhi, "Waxaa jirta daawaynta daawaynta oo aad u liidata oo la maamulo ka dib soo noqoshada joogtada ah." Marka la eego saadaasha liidata ee bukaanada dib u soo noqda ka dib markay helaan daawaynta carnitine, waxaa jira baahi degdeg ah oo aan la daboolin oo loogu talagalay daaweynta cusub.
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 qanjirada unugyada 'Hodgkin' 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, Cudurka sanbabada ee daba-dheeraada/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.
Patients received either 1 x 106 (dose level 1) or 3 x 106 (dose level 2) of the CD22-targeted drug (dose level 2). Prior to infusion, patients received intravenous fludarabine (30 mg/m2) and cyclophosphamide (500 mg) to administer lymphodepleting chemotherapy.
The primary objectives of the study were manufacturing feasibility, the phase 2 dose recommendation, safety, and toxicity. The investigator-assessed ORR, duration of response, progression-free survival (PFS), overall survival (OS), CAR T associated toxicity, CD22 antigen expression, CAR-positive cell levels in the blood, and serum cytokine profiling were secondary endpoints.
41 ka mid ah bukaannada diiwaangashan, badeecada CAR T-cell ayaa si guul leh loo soo saaray 38 (95%), maadaama 2 ay lahaayeen unugyo T ku filan oo loogu talagalay leukapheresis. Celceliska muddada u dhaxaysa leukapheresis iyo faleebo waxay ahayd 18 maalmood.
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 qanjiro. 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.
Waqtiga daba-galka dhexdhexaadka ah ee dhammaan bukaannada wuxuu ahaa 18.4 bilood (qiyaastii: 1.5-38.6), markaas ORR wuxuu ahaa 68% iyo heerka CR wuxuu ahaa 53%. Dhexdhexaadiyaha PFS wuxuu ahaa bilaha 2.9 (95% isku-kalsoonida [CI], 1.7-NR) iyo dhexdhexaadiyaha OS wuxuu ahaa 22.5 bilood (95% CI, 8.3-NR).
Heerka qiyaasta 1 (n = 29), bukaanada ayaa la raacay dhexdhexaad ah 14.1 bilood (kala duwan, 1.5-38.6), oo muujinaya 66% ORR iyo 52% CR heerka. Badbaadinta horumarka dhexdhexaadka ah ee dhexdhexaadka ah waxay ahayd bilaha 3.0 (95% CI, 1.6-NR) iyo badbaadada guud ee dhexdhexaadku waxay ahayd NR (95% CI, 8.3-NR).
Heerka qiyaasta 2 (n = 9), dabagalka dhexdhexaadka ah wuxuu ahaa 27.1 bilood (qiyaastii: 24.7-33.5), ORR wuxuu ahaa 78%, iyo heerka CR wuxuu ahaa 55%. Dhexdhexaadka PFS wuxuu ahaa 2.6 bilood (95% u dhexeeya kalsoonida: 1.3-NR) iyo OS dhexdhexaadintu waxay ahayd 22.5 bilood (95% inta u dhaxaysa kalsoonida: 5.5-NR).
Kaliya 1 ka mid ah 20-kii bukaan ee helay CR ayaa dib u soo noqday marka la eego goynta xogta, taas oo muujinaysa in CRs ay waaranayaan. Bishii saddexaad, dhammaan bukaannada horumar ka sameeyay daawaynta way sameeyeen.
In 95% of patients, cytokine sii daayo 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 hemophagocytic lymphohistiocytosis.
Hal bukaan oo heerka qiyaasta 2 ah ayaa u dhintay sepsis maalintii 40, iyo hal bukaan ayaa soo saaray daawaynta la xiriirta myelodysplasia/ ba'an myeloid leukemia iyada oo aan caddayn LBCL dib u soo noqoshada 11 bilood ka dib markii la helay daawaynta CD22-dugsiga.
Heerka qiyaasta qiyaasta lagu taliyey ee wajiga 2 ayaa la go'aamiyay inuu yahay 1.
Xogtii hore loo daabacay ayaa tafaasiil ka bixisay daawaynta saddexdii bukaan ee hore.
Dhammaan labada bukaan waxay lahaayeen astaamo halis sare leh waxayna heleen ugu yaraan shan khad daweyn oo hore, oo ay ku jiraan daawaynta unugyada CAR T-cell ee CD19 Mid ka mid ah bukaannada ayaa hore u helay laba daawaynta CAR T-cell, kan labaad oo lagu beegsaday CD19 iyo CD20. Dhammaan saddexda bukaan waxay gaadheen CR, iyadoo bukaanku 3 uu gaadhay CR maalintii 28. CRs ayaa la hayay in ka badan saddex sano.
Frank waxa kale oo uu xusay in "fiditaanka CAR22 uu toban laab ka weyn yahay kana sii dheer yahay CAR19."
To learn more about patients who have relapsed after CD19-directed CAR T-cell therapy, a planned multicenter phase 2 trial of this agent is being set up. The trial will likely begin this summer.
tixraacyada
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, iyo al. CD22-ku-daweenta CAR T-cell waxay keentaa cafis dhammaystiran oo CD19-ku-jiro CAR-cell lymphoma weyn oo B-cell ah. Dhiiga. 2021;137(17):2321-2325. doi:10.1182/blood.2020009432
