|The following article features coverage from the American Association for Cancer Research (AACR) 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
Results from an updated analysis of patients enrolled in a phase 1 trial of anti-CD22 chimeric antigen receptor (CAR) T-cell (CAR-T) therapy in pediatric and young adults with recurrent or refractory CD22-expressing B-cell malignancies (ClinicalTrial.gov Identifier: NCT02315612) confirmed initial reports of high anticancer activity, but also demonstrated a number of novel toxicities — including grade 5 adverse events in 2 patients. The findings of this study were presented at the American Association for Cancer Research (AACR) Annual Meeting 2019.
CD19-targeted therapy has revolutionized the treatment of patients with B-cell malignancies. However, other approaches are needed for patients who are resistant to or relapse following anti-CD19 therapy.
Patients enrolled in this study had a diagnosis of follicular lymphoma, acute lymphoblastic leukemia, non-Hodgkin lymphoma, or large cell lymphoma and were deemed incurable by standard therapy. A history of allogeneic hematopoietic stem cell transplantation (HSCT), as well as previous treatment with anti-CD19 CAR-T cell therapy, were allowed. In the dose-escalation portion of the study, anti-CD22 CAR-T cell therapy was administered, following lymphodepletion with fludarabine and cyclophosphamide, at 3 dose levels, 2 of which incorporated an interim manufacturing modification involving the use of CD4/CD8 bead T-cell selection (TCS).
Of the 52 patients included in this analysis, the median patient age was 18.1 years, 36 (69.2%) had previously undergone HSCT. Prior treatment with anti-CD19 CAR-T cell therapy, blinatumomab (ie, a CD3/CD19 bispecific T-cell engager [BiTE] against CD3 and CD19), and inotuzumab (ie, a CD22 antibody-drug conjugate) was received by 57.7%, 42.3%, and 26.9% of patients, respectively. In addition, 5.8% of patients had received prior anti-CD22 CAR-T cell therapy.
More than half of the overall patient cohort had a CD19-negative population, including 2 patients who had not undergone prior treatment with targeted therapy, and nearly three-quarters of patients had at least M2 marrow at baseline.
The majority of patient experienced cytokine release syndrome (88.4%), with grade 3 or grade 4 CRS observed in 10.9% of patients. Tocilizumab (ie, an antibody against the cytokine interleukin-6) and steroids were administered to 36.5% and 32.7% of patients, respectively.
Of the novel toxicities observed in this study, capillary leak syndrome was observed in 3 patients (5.8%), with 1 patient (1.9%) experiencing a grade 5 event. Other novel toxicities included hemophagocytic lymphohistiocytosis-like manifestations (18 individuals; 34.6%), symptomatic coagulopathy (8 individuals; 15.4%), and atypical hemolytic uremic syndrome (2 individuals; 3.8%).
The overall rate of complete remission rate was 72.5%, with 84% of patients treated at current dose level (3 x 105 transduced T cells/kg TCS) achieving a complete remission.
Interestingly, among those patients achieving a complete remission were some who had not responded to prior anti-CD19 CAR-T cell therapy and/or blinatumomab. An ongoing complete remission of more than 3 years was observed in 1 patient. Relapse following treatment with anti-CD22 CAR-T therapy occurred at a median of 6 months following treatment initiation in 23 (64%), with most relapses resulting from CD22 modulation. Twelve patients underwent HSCT following anti-CD22 CAR-T cell therapy.
“Results from our study support further testing of this CD22 CAR in a phase 2 clinical trial,” the authors noted in conclusion.
Read more of Cancer Therapy Advisor‘s coverage of AACR 2019 meeting by visiting the conference page.
- Shah NN, Shalabi H, Yates B, et al. Phase I CD22 CAR T-cell trial updates. Presented at: American Association for Cancer Research Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. Abstract LB146/3.