InO is effective and well tolerated in heavily pretreated children and adolescents with R/R CD22-positive B-ALL. SOS after hematopoietic stem-cell transplantation and prolonged cytopenias were notable. CD22 modulation was identified as a mechanism of resistance. Expanded study of InO combined with chemotherapy is underway.
Three patients had relapsed BCP-ALL after both haploidentical HSCT and autologous CD19 CAR-T cell, 3 after haploidentical HSCT, 2 after autologous CD19 CAR-T cell, 3 after intensive chemotherapy +/- blinatumomab (n=2)...Five (45%) pts received treosulfan-based regimen, while TBI-based regimen was used in 6 (55%) pts. GvHD prophylaxis included tocilizumab and abatacept...The infusions did not compromise engraftment and GVHD control, while specific CAR-T toxicity was mild and manageable. We have documented allogeneic haploidentical CAR-T expansion and persistence.
Prior to InO, blinatumomab was administered in n=14 and local irradiation in n=5 pts...Sinusoidal obstruction syndrome (SOS) was reported in 1 patient after transplant; conditioning in this patient consisted of treosulfan/fludarabine/thiotepa... This outcome analysis demonstrates that treatment with InO is an effective and promising approach in r/r-ALL patients with EM disease. However, allo-SCT alone seems not to be effective in maintaining disease control. Thus, autologous chimeric antigen receptor T-cells or advanced bi-specific antibodies as consolidation therapy should be evaluated in the future.
Three patients had relapsed BCP-ALL after both haploidentical HSCT and autologous CD19 CAR-T cell, 3 after haploidentical HSCT, 2 after autologous CD19 CAR-T cell, 3 after intensive chemotherapy +/- blinatumomab (n=2)...Five (45%) pts received treosulfan-based myeloablative preparative regimen, while TBI-based regimen was used in 6 (55%) pts. GvHD prophylaxis included tocilizumab at 8 mg/kg on day -1 and abatacept at 10 mg/kg on day -1, +7, +14, +28...We have documented allogeneic haploidentical CAR-T expansion and persistence. Prospective testing of the approach is warranted.
P1, N=1, Terminated, Second Affiliated Hospital of Xi'an Jiaotong University | N=28 --> 1 | Trial completion date: May 2023 --> May 2021 | Recruiting --> Terminated; Suitable patients were not recruited
Having demonstrated the efficacy and safety of the lead CD22 TCR candidate, we now will analyze efficiency in a xenograft model and on material of patients that relapsed after a CD19 CAR T cell therapy and of acute lymphoblastic leukemia (ALL) -relapsed children after treatment with the CD22 targeting agent inotuzumab. Patients that have relapsed from CD19 or CD22 CAR therapy might be rescued by the treatment with CD22 TCR T cells. We here demonstrate the development of a CD22 candidate TCR for further preclinical development and translation into early clinical trials in patients with CD22-positive B cell malignanices.
This drug combination is not possible within a therapeutically useful range of doses due to toxicities. Antitumor activity was observed in heavily pretreated patients (ClinicalTrials.gov, Identifier NCT01535989).
5 months ago
Clinical • P1 data • Journal • Combination therapy
We then performed a set of experiments and observed that while IS7- CAR killed less rapidly than m971-CAR in vitro, it was as efficient in controlling lymphoma xenograft models in vivo. Thus, IS7-CAR is a potential alternative candidate for treatment of refractory B-cell malignancies.
InO demonstrated a favorable benefit-risk profile versus SC in patients with higher and lower CD22 expression. Patients with high CD22 expression and normal cytogenetics benefited the most from InO therapy.
Circulating CD19-negative CD22-positive precursors are commonly detected at low levels in peripheral blood samples, they should be distinguished from B-ALL MRD especially in the setting of CD19-targeted therapy.