New Clinical Research on Chimeric Antigen Receptor (CAR) T-Cell Therapy Presented at 60th American Society of Hematology Annual Meeting

In Clinical Studies News by Barbara Jacoby

Source:    Yadira Galindo, Health Journalist

The 60th American Society of Hematology (ASH) Annual Meeting, the largest international conference and exhibition in the field of hematology, is currently taking place at the San Diego Convention Center.  Dr. Peihua Lu, the Medical Executive President of the Hebei Yanda Lu Daopei Hospital, and Dr. Xian Zhang from the same institution were invited by the organizer to present their outstanding clinical research on chimeric antigen receptor (CAR) T-cell therapy on December 2, 2018.  The Lu Daopei Hospital is one of the most prominent and dominant medical centers in China and the Asia Pacific region for bone marrow hematopoietic stem/progenitor cell transplant and cellular immunotherapy.

CAR T-cell therapy involves genetically modifying a patient’s T-cells to recognize a specific antigen found on tumor cells and kill them.

During a podium presentation, Dr. Peihua Lu reported results of a clinical study titled “A Feasibility and Safety Study of CD19 and CD22 Chimeric Antigen Receptors-Modified T Cell Cocktail for Therapy of B Cell Acute Lymphoblastic Leukemia (B-ALL).”  Fifteen patients (including five children and 10 adults) with CD19+CD22+ relapsed or refractory B-ALL were treated at Lu Daopei Hospital with the chemotherapy drugs fludarabine and cyclophosphamide, followed by a cocktail of CAR T-cell infusion with CD19 CAR-T and CD22 CAR-T.  The CD22 CAR construct includes a single chain variable fragment (ScFv) from a monoclonal antibody against the human protein PD-L1 which attempts to reduce the exhaustion of CAR T-cells by blocking the PD-1/PD-L1 pathway, thereby enhancing the persistence of infused CAR T-cell engraftment.  Between days 20 to 30, after CAR-T infusion, 15 out of 15 patients (100%) achieved complete remission (CR) or incomplete CR (CRi) while 14 out of 15 patients (93.3%) had negative minimal residual disease (MRD).  In this cohort of patients with very high CR rate, they also experienced very low treatment-related toxicity: 13 out of 15 patients developed cytokine release syndrome (CRS), a systemic inflammatory response, at a grade <2, and central nervous system (CNS) Grade 0.  Dr. Lu concluded that this study has demonstrated technical feasibility, high efficacy and low toxicities of CD19 and CD22 CAR-T cocktail in treating patients with CD19+CD22+ relapsed or refractory B-ALL.

Another clinical study performed at the Lu Daopei Hospital, titled “Efficacy and Safety of CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy for B-Cell Acute Lymphoblastic Leukemia (B-ALL) in a Large Cohort Including Patients with Extramedullary Disease (EMD), High Leukemia Burden (HLB), BCR-ABL (+) Mutation, TP53 Mutation, and Post-Transplant Relapse” was presented by Dr. Xian Zhang at this ASH Annual Meeting as an oral presentation.  A cohort of 87 B-ALL patients with high-risk features (including those listed in the title) were given a single infusion of CD19 CAR T-cells.  After 30 days of CAR-T therapy, 76 out of 83 patients (91.6%) achieved CR or Cri, and 70 out of 76 patients achieved MRD-negative CR.  One-year overall survival (OS) was 76.5% and relapse-free survival (RFS) was 62.6%.  This cohort of patients also experienced low side effect and toxicity profile: grade 0-2 CRS incidence was 82%, and grade 3-4 was only 16%.  Dr. Zhang concluded that this cohort of relapsed/refractory B-ALL patients with high-risk features (such as EMD, HLB, BCR-ABL+, TP53+, and relapse after allogeneic hematopoietic stem cell transplant) achieved high CR rate with manageable CRS after CD19 CAR-T treatment.  Overall, RFS was superior for patients bridging to allogeneic hematopoietic stem cell transplant after CAR T-cell treatment than for patients receiving CAR-T alone.

These two studies from Lu Daopei Hospital have demonstrated superior clinical outcomes and high safety profile in CAR-T therapy.  Both presentations by Dr. Peihua Lu and Dr. Xian Zhang were very well received by their peer audience.