CD22-CAR Shows Promise in LBCL After CD19 Relapse

CD22 CAR, an investigational autologous CD22-directed chimeric antigen receptor T-cell (CAR-T) therapy, has produced high response rates in patients with large B-cell lymphoma (LBCL) who previously relapsed after receiving CD19-directed CAR-T therapy or who had CD19-negative disease. The data, from a phase 1 clinical trial (NCT04088890), were presented by Matthew J. Frank, MD, PhD, assistant professor of medicine, division of BMT & Cellular Therapy, Division of Stanford Cancer Institute, at the 2023 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Orlando, Florida, February 15-19, 2023.

Among the 38 patients who received treatment with CD22 CAR, 29 patients received the trial’s lower dose (DL1) of 1x10⁶ CAR+ cells/kg and 9 patients received the trial’s higher dose (DL2) of 3x10⁶ CAR+ cells/kg. The overall response rate (ORR) was 68% and the overall complete response (CR) rate was 53%, as of the December 27, 2022, cutoff date. Median progression free survival (PFS) was 2.9 months (95% CI) and median overall survival (OS) was 22.5 months (95% CI). Frank noted that the ORR, CR rate, PFS, and OS were similar between patients in DL1 and DL2. The follow-up for all treated patients ranged from 1.5 months to 38.6 months (median, 18.4), with a median follow-up of 14.1 months in DL1 and a median follow-up of 27.1 months in DL2. Frank additionally highlighted that CRs were typically durable, with only 1 of the patients who achieved a CR having relapsed.

In terms of safety, DL2 was found to be generally more toxic than DL1. Among participants treated at DL2, 7 patients (78%) experienced cases of grade 2 cytokine release syndrome (CRS) and 1 patient (11%) experienced a grade 3 case of CRS. In DL1, there were no cases of grade 3 CRS and only 48% of patients (n=14) experienced cases of grade 2 CRS. Altogether, there were 14 patients (37%) who experienced cases of grade 1 CRS across all treated participants. Furthermore, 33% of patients (n=3) treated at DL2 experienced hemophagocytic lymphohistiocytosis-like (carHLH) toxicities, while only 7% of patients (n=2) treated at DL1 experienced carHLH toxicities. One patient (11%) treated at DL2 experienced a case of grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS), and 1 patient (3%) treated at DL1 experienced a case of grade 2 ICANS. There were 3 cases of grade 1 ICANS across all treated patients. Frank noted that 1 patient in DL2 died of sepsis at 40 days after treatment and 1 patient developed treatment-related MDS/AML without evidence of LBCL relapse at 11 months following infusion.

“We predominantly used anakinra and steroids [to treat the carHLH toxicities],” Frank said in response to an audience question following the presentation. “And I think that's likely what's going to be the recommended treatment for patients who have non-life threatening carHLH. But we did have 1 patient who actually died of Klebsiella pneumoniae and that was after she was recovering from the carHLH, but because of the long steroid course was, I think, susceptible for infections. So we've instituted prophylactic antibiotics after that case, so everybody who's developed that afterwards was on antibiotics to help mitigate that problem.”

The ages of the 38 participants treated with CD22 CAR ranged from 25 years to 84 years (median, 65). Twenty-one (55%) of the patients were male and all of the patients had and Eastern Cooperative Oncology Group Performance Score of 1 or lower. The population was heavily pretreated, with patients having received 3 to 8 prior lines of therapy (median, 4). Eleven of the patients (29%) had no prior CR to any line of therapy, 7 patients (18%) had previously received autologous hematopoietic stem cell transplant, and 37 patients (97%) had received prior CD19 CAR therapy. Frank noted that 6 patients (21%) in DL1 had disease classified with double-hit status, while no patients in DL2 had double-hit status disease. He also pointed out that 79% of patients had elevated lactate dehydrogenase levels prior to lymphodepleting chemotherapy. The median time from leukapheresis to CAR22 infusion was 18 days. Four patients received bridging therapy between enrollment and lymphodepletion.

“CAR22 safety appears comparable with CAR19...” Frank concluded. “DL1 is the recommended phase 2 dose.... A multicenter phase 2 clinical trial is anticipated to open in the summer of 2023 for patients who have relapsed after CAR19 therapy.”

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REFERENCE

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 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.February 15-19, 2023; Orlando, FL. Abstract 2