Program: Oral and Poster Abstracts
Session: 703. Adoptive Immunotherapy: CAR-T Toxicity and Clinical Trials
Design: Children and young adults with relapsed/refractory CD22+ hematologic malignancies were eligible. Study endpoints included toxicity, feasibility, and clinical responses. All enrolled subjects underwent autologous leukopheresis for peripheral blood mononuclear cells. Cells were then CD3+ enriched and cultured in the presence of anti-CD3/-CD28 beads followed by lentiviral vector supernatant containing the anti-CD22 (M971BBz) CAR, with culture duration of 7-10 days. Subjects began lymphodepleting chemotherapy with fludarabine 25 mg/m2 on Days –4, –3 and –2 and cyclophosphamide 900 mg/m2 on day –2 followed by cell infusion on Day 0. Dose level 1(DL-1) started at 3 x 105 transduced T-cells/recipient weight (kg), with DL- 2 at 1 x 106transduced T cells/kg, respectively.
Results: We report on outcomes for the first 9 subjects enrolled and treated. The median age was 20 years (range, 7-22 years), and all had CD22+ ALL. All 9 subjects had previously undergone at least one prior allogeneic hematopoietic stem cell transplant, and 2 patients had received 2 prior transplants. Seven subjects had previously received treatment with anti-CD19 CAR-T cell therapy of whom 6 had a CD19 negative/dim antigen escape. All subjects had CD22 expression on > 99% of their malignancy, with a median site density of 2589 molecules per cell (range 846-13452). Dose-escalation was as follows: 6 subjects treated at DL-1 due to expansion at this level following DLT in the second subject with grade 3 diarrhea; 3 subjects treated at DL-2 without DLT. CAR expansion and cytokine release syndrome (CRS) was seen in 6 patients with a maximum CRS grade 2. Anti-CD22 CAR cells were detected in the peripheral blood, CSF and bone marrow of all responders. Clinical responses were evaluated at day 28 (+/- 4 days). Four of 9 (44%) subjects evaluable for response attained a complete marrow remission, all of whom were MRD negative. This included all 3 subjects treated at the second dose level with a sustained remission at 3 months.
Conclusions: This first-in-human anti-CD22 CAR T-cell therapy is safe, feasible and clinically active in patients with leukemia who have undergone prior CAR therapy. MRD negative complete remissions were seen in patients who were both CAR-naïve or had previously been treated with anti-CD19 CAR and were CD19 negative. Accrual is ongoing.
Disclosures: Lee: Juno: Honoraria. Mackall: Juno Therapeutics: Patents & Royalties: CD22 CAR; Unum Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Pfizer-Servier: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Glaxo-Smith-Kline: Membership on an entity's Board of Directors or advisory committees; Vor Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.
See more of: Adoptive Immunotherapy
See more of: Oral and Poster Abstracts