I bhFeabhrary 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 Teiripe CAR T-chill. 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 Teiripe CAR T-chill 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.
Dúirt Frank, “Tá ganntanas teiripí leigheasacha a riartar tar éis athiompaithe ainsealacha.” I bhfianaise droch-prognóis na n-othar a thagann ar ais tar éis teiripí carnitine a fháil, tá éileamh práinneach ar theiripí núíosacha gan shásamh.
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 lymphoma neamh-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, leoicéime lymphocytic ainsealach/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.
As 41 othar cláraithe, rinneadh an táirge T-chealla CAR a mhonarú go rathúil do 38 (95%), toisc nach raibh cealla T leordhóthanacha ag 2 acu le haghaidh leoicféarais. Ba é 18 lá an meánréimhse idir leukapheresis agus insileadh.
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 liomfóma. 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.
Ba é 18.4 mí (raon: 1.5-38.6) an t-am leantach airmheánach do na hothair go léir, agus ba é an ráta ORR ná 68% agus 53% an ráta CR. Ba é an PFS airmheánach ná 2.9 mí (95% eatramh muiníne [CI], 1.7-NR) agus ba é 22.5 mí an t-airmheán OS (95% CI, 8.3-NR).
Ag leibhéal dáileog 1 (n = 29), lean na hothair ar feadh 14.1 mí airmheán (raon, 1.5-38.6), rud a léirigh ORR 66% agus ráta CR 52%. Ba é meánmharthanacht saor ó dhul chun cinn ná 3.0 mí (95% CI, 1.6-NR) agus ba é meánmharthanacht iomlán NR (95% CI, 8.3-NR).
Ag leibhéal dáileoige 2 (n = 9), ba é an meán leantach 27.1 mí (raon: 24.7-33.5), ba é an ORR 78%, agus b'ionann an ráta CR 55%. Ba é an PFS airmheánach ná 2.6 mí (95% eatramh muiníne: 1.3-NR) agus ba é an t-idirmheánach OS 22.5 mí (95% eatramh muiníne: 5.5-NR).
Ní raibh ach 1 as an 20 othar a bhain CR amach tar éis dul i léig arís mar gheall ar an scoite sonraí, rud a thug le fios go bhfuil CR marthanacha. Faoin tríú mí, bhí sé sin déanta ag gach othar a raibh dul chun cinn déanta acu ar chóireáil.
In 95% of patients, siondróm scaoileadh cytokine 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.
Fuair othar amháin ag leibhéal dáileog 2 bás le sepsis ar an lá 40, agus d'fhorbair othar amháin myelodysplasia a bhain le cóireáil / leoicéime myeloid géarmhíochaine gan fhianaise ar athiompaithe LBCL 11 mí tar éis dó teiripe CD22-threoraithe a fháil.
Socraíodh gurb é an leibhéal dáileoige molta do chéim 2 ná 1.
Thug faisnéis a foilsíodh roimhe seo mionsonrú ar chóireáil na gcéad trí othar.
Bhí tréithe ard-riosca ag an dá othar agus fuair siad cúig líne cóireála roimhe seo ar a laghad, lena n-áirítear teiripe T-chealla CAR faoi stiúir CD19. Fuair ceann de na hothair dhá theiripe T-chealla CAR cheana féin, agus dhírigh an dara ceann ar CD19 agus CD20. Bhain na trí othar CR amach, agus bhain othar 3 CR amach ar lá 28. Coinníodh CR ar feadh níos mó ná trí bliana.
Thug Frank faoi deara freisin go bhfuil “leathadh CAR22 faoi dheich oiread níos mó agus níos seasmhaí ná 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.
tagairtí
1. Frank MJ, Sahaf B, Baird J, et al. CD22 CAR T cell therapy induces durable remissions in patients with large B lymphoma cille 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. Spreagann teiripe T-chealla CAR faoi stiúir CD22 loghadh iomlána i limfóma mór B-chealla teasfhulangacha CAR-threoraithe CD19. Fola. 2021;137(17):2321-2325. doi:10.1182/blood.2020009432
