Phase I trial of 19-28z chimeric antigen receptor modified T cells (19-28z CAR-T) post-high dose therapy and autologous stem cell transplant (HDT-ASCT) for relapsed and refractory (rel/ref) aggressive B-cell non-Hodgkin lymphoma (B-NHL).

Abstract

8515 Background: HDT-ASCT is the standard of care for patients with rel/ref diffuse large B-cell lymphoma (DLBCL). Herein, we report safety data on the first 8 patients of our phase I clinical trial of 19-28z CAR-T post HDT-ASCT for poor-risk rel/ref aggressive B-NHL (NCT01840566). Methods: Eligibility for this study includes rel/ref aggressive B-NHL chemosensitive to salvage therapy with: 1) FDG-PET (+) following 2 cycles of salvage therapy or 2) bone marrow involvement of B-NHL. T cells were retroviral transduced with anti-CD19 scFV linked to CD28 and CD3ζ signaling domains. Patients underwent BEAM conditioned HDT-ASCT and 19-28z CAR-T were administered on days +2 and +3. Results: See table for patient characteristics and results. Seven patients were treated at dose level #1 (5 x106 19-28z CAR-T/kg) with one dose-limiting toxicity (DLT) of prolonged grade III-IV cytopenias and non-relapse mortality (NRM) of mucormycosis pneumonia. One patient treated at dose-level #2, 1 x107 CAR-T/kg, experienced a DLT related to severe cytokine-release syndrome (CRS) and fully recovered. Fifty percent of the patients experienced CRS effectively treated with tocilizumab +/- corticosteroids. All patients engrafted neutrophils post-HDT-ASCT. Five of eight remain alive and progression-free at the time of this analysis. Conclusions: This is the first study of 19-28z CAR-T cells following consolidative HDT-ASCT for poor-risk rel/ref aggressive B-NHL. The use of 19-28z CAR T cells is a promising approach in poor-risk PET+ B-NHL patients undergoing HDT-ASCT with manageable CRS. Clinical trial information: NCT01840566. Patient Age Disease Disease at HDT-ASCT Dose Level CRS Peak CRP (mg/dL) Status Post- HDT-ASCT 1 34 transformed follicular lymphoma (tFL) PET(+ )PR 1 Yes 27.3 CR/18 mo 2 68 DLBCL PET(+) PR 1 No 16.5 CR/17 mo 3 56 transformed marginal zone lymphoma PET(+) PR, bone marrow (BM) involved 1 No 17.6 CR/11 mo 4 59 tFL/double-hit (DHL) PET(+) PR 2 Yes 43.1 CR/10 mo 5 66 DLBCL PET(+) PR 1 No 5 CR/11mo 6 64 CD5+ DLBCL PET(+) PR 1 No 7.9 POD/6 mo 7 65 Burkitt lymphoma PET(+) PR BM involved 1 Yes 11.8 POD/2 mo 8 56 DLBCL/DHL PET (+) PR 1 Yes 18.1 NRM/d38