2020 dec: The University of Texas MD Anderson Cancer Center researchers discovered that axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, is a safe and effective first-line therapy for patients with high-risk large B-cell lymphoma (LBCL), a group in desperate need of new and effective treatments.
Disse resultater blev præsenteret på American Society of Hematologys virtuelle 2020 årsmøde.
Traditionally, around half of patients with high-risk LBCL, a subgroup of the disease in which patients have double- or triple-hit lymfom or additional clinical risk factors identified by the International Prognostic Index (IPI), have not achieved long-term disease remission with standard treatment approaches such as chemoimmunotherapy.
This trial represents a step toward making CAR T-cellebehandling a first-line treatment option for patients with aggressive B-cell lymphoma,” said Sattva S. Neelapu, M.D., professor of Lymphoma and Myeloma. “At the moment, patients with newly diagnosed aggressive B-cell lymphoma get chemotherapy for about six months. CAR T-cellebehandling, if successful, may make it a one-time infusion with treatment completed in one month.
Baseret på nøgleforskningen ZUMA-1, er Axi-cel i øjeblikket godkendt til behandling af personer med recidiverende eller refraktær LBCL, som allerede har haft to eller flere linjer af systemiske behandlinger. ZUMA-12-studiet er et fase 2 åbent, enkelt-arm, multicenter-studie, der bygger på resultaterne af ZUMA-1-studiet for at vurdere brugen af axi-cel som førstelinjebehandling til patienter med højrisiko-LBCL.
Ifølge ZUMA-12-interimstudiet havde 85 procent af patienterne behandlet med axi-cel et samlet respons, og 74 procent havde et fuldstændigt respons. Efter en median opfølgning på 9.3 måneder udviste 70 % af de rekrutterede patienter et vedvarende respons ved data cutoff.
Reduktion af antallet af hvide blodlegemer, encefalopati, anæmi og cytokinfrigivelsessyndrom were the most common side effects linked with axi-cel treatment. By the time the data was analysed, all adverse events had been resolved.
Furthermore, when compared to when the immunotherapy products were generated from patients who had already received several lines of chemotherapy, the peak level of CAR T cells present in the blood, as well as the median CAR T cell expansion, were higher in this trial of first-line CAR T-cellebehandling.
"Denne T-celle-fitness kunne være forbundet med større terapeutisk effektivitet, hvilket resulterer i bedre patientresultater," tilføjede Neelapu.
Efter de fremragende foreløbige resultater af ZUMA-12 planlægger forskerne at fortsætte med at følge op med patienterne for at sikre, at deres reaktioner på medicinen er langvarige.
“A randomised clinical trial would be required to definitely demonstrate that CAR T cell therapy is superior to existing standard of care with chemoimmunotherapy in these high-risk patients if the responses are persistent after prolonged follow-up,” Neelapu said. It also begs the question of whether CAR T cell treatment should be tested in intermediate-risk patients with big B-celle lymfom.
