Promising Therapy for Patients With Refractory Primary Mediastinal B-cell Lymphoma

Anti-cancer therapeutics, such as chimeric antigen receptor (CAR) modified T cells, can be engineered to target tumor-associated antigens to attack and kill cancer cells. This allows for an improved precision medicine approach to treating cancer. Moffitt Cancer Center physician-scientist Fredrick L. Locke, will present interim results from cohort 2 of the phase 2 portion of the ZUMA-1 study, which uses CAR-T therapy for patients with refractory primary mediastinal B-cell lymphoma and transformed follicular lymphoma, during the American Society of Hematology Annual Meeting in San Diego.

The ZUMA-1 study utilizes KTE-C19 which is an autologous chimeric antigen receptor (CAR) T cell therapy. During KTE-C19 CAR-T therapy, T cells are isolated from a patient's blood and genetically engineered in Kite's laboratory to target the CD19 protein that is found on lymphoma cells. The genetically engineered T cells are then infused within the patient that they were originally harvested from. The KTE-C19 T cells are able to recognize cancerous lymphoma cells that express CD19 and target them for destruction.

The phase 1 portion of the ZUMA-1study revealed that KTE-C19 was tolerable and produced ongoing remissions in B-cell non-Hodgkin lymphoma patients (Locke et al, Abstr. 1048O, ESMO Congress 2016). The phase 2 portion of the study consists of two cohorts: cohort 1 for patients with chemo-refractory Diffuse Large B cell Lymphoma; and cohort 2 for patients with chemo-refractory primary mediastinal B-cell lymphoma or transformed follicular lymphoma.

As of June 16, six patients with refractory primary mediastinal B-cell lymphoma or transformed follicular lymphoma were treated in cohort 2 with KTE-C19. The patients were highly refractory to prior treatments and included three patients who were refractory to second-line or greater therapy and three patients who relapsed after autologous stem cell transplants.

KTE-C19 therapy resulted in promising clinical activity in these patients. With a median follow-up period of 3.2 months, all six patients achieved a complete remission. KTE-C19 treatment also resulted in manageable toxicities that were generally reversible. Grade 3 treatment-emergent adverse events occurred in 17% of patients and grade 4 treatment-emergent adverse events occurred in 67% of patients. All six patients experienced cytokine release syndrome; however, all cases were grade 1 or 2. Neurotoxicity occurred in 67% of patients and 33% of the cases were grade 3.

Source-Eurekalert