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).

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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.

Reference

  1. 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.