S230: cd22 car t cell therapy is safe and effective in patients with large b cell lymphoma who have relapsed after cd19 car t cell therapy.

Background: Patients with relapsed/refractory large B-cell lymphoma (LBCL) who progress after CD19 CAR T-cell therapy (CAR19) have poor outcomes. CD22 is expressed on the majority of B-cell lymphomas. Here, we report on the evaluation of an autologous CAR T-cell therapy targeting CD22 (CAR22) for the treatment of adult patients with R/R LBCL who have predominantly relapsed after CAR19. Aims: The primary aims of this trial assessed the ability to successfully manufacture CAR22 and to determine the initial safety of the CAR22. Key secondary aims included overall response rate, complete response rates, progression free survival, and overall survival. Methods: This single-institution trial (NCT04088890) evaluated a CAR22 constructed from the m971 single chain variable fragments and 41BB/CD3z endodomains. After lymphodepletion (LD) with fludarabine 30 mg/m2 and cyclophosphamide 500 mg/m2 for 3 days from Day -5 to -3, patients were infused with cryopreserved CAR T-cells after a 7- to 12-day closed manufacturing process utilizing the CliniMACS Prodigy device (Miltenyi). Results: We have now completed enrollment of this phase 1 trial. 41 patients have enrolled and 40 patients underwent apheresis for CAR22 manufacturing. One patient withdrew and pursued alternative therapy. Successful manufacturing was achieved in 38 (95%) of 40 subjects. With a median follow-up of 18.4 (1.5-38.6) months, 38 patients with LBCL [n=29 at dose level 1 (DL1), 1x106 CAR+ cells/kg; n=9 at dose level 2 (DL2), 3x106 CAR+ cells/kg] have been treated with a median age of 65 years (range, 25-84) and median of 4 (range 3-8) prior lines of therapy. 37 (97%) progressed after prior CAR19 therapy and 30 (79%) had elevated pre-LD lactate dehydrogenase. 36 (95%) patients experienced cytokine release syndrome (CRS); at DL1, no patient experienced greater than grade 2 CRS. Five patients (13%) experienced immune effector cell-associated neurotoxicity syndrome (ICANS); all cases were Grade 1-2 and resolved within 2 days. CAR-HLH, a syndrome of high ferritin, cytopenias, coagulopathy, and liver abnormalities, occurred in 3 (33%) patients at DL2 and in 2 (7%) at DL1; all 5 patients achieved a complete response. One patient at DL2 had a Grade 5 infectious event in the setting of ongoing car-HLH and pancytopenia. Due to higher rates of car-HLH and higher-grade CRS at DL2, DL1 is the recommended phase 2 dose. The overall response (ORR) and complete response (CR) rates are 68% (n=26) and 53% (n=20). Between DL1 and DL2, the ORR (66% (n=19) vs. 78% (n=7)) and CR rates (52% (n=15) vs. 56% (n=5)) were similar. PFS and OS are shown in Figure 1. Only 1 of the 20 patients who achieved CR has relapsed to date. Correlative data will be presented at the meeting. 6 of 7 subject had down-regulation or absence of CD22 at the time of relapse. Higher Peak CAR22 expansion and higher AUC was associated with ORR and the development of higher grade CRS and car-HLH. Summary/Conclusion: CAR22 is a highly effective and safe salvage therapy for patients with CAR19-refractory LBCL. A multicenter phase 2 clinical trial is planned to open in 2023.Keywords: CAR-T, Cellular therapy, DLBCL