December 2020: 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.
Tieto zistenia boli prezentované na virtuálnom výročnom stretnutí Americkej hematologickej spoločnosti v roku 2020.
Traditionally, around half of patients with high-risk LBCL, a subgroup of the disease in which patients have double- or triple-hit lymfóm 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 bunková terapia 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 bunková terapia, if successful, may make it a one-time infusion with treatment completed in one month.
Na základe kľúčového výskumu ZUMA-1 je Axi-cel v súčasnosti licencovaný na liečbu ľudí s recidivujúcim alebo refraktérnym LBCL, ktorí už podstúpili dve alebo viac línií systémovej liečby. Štúdia ZUMA-12 je otvorená, jednoramenná, multicentrická štúdia fázy 2, ktorá stavia na zisteniach štúdie ZUMA-1 s cieľom posúdiť použitie axi-celu ako liečby prvej línie u pacientov s vysokorizikovým LBCL. .
Podľa priebežnej štúdie ZUMA-12 malo 85 percent pacientov liečených axi-celom celkovú odpoveď a 74 % malo úplnú odpoveď. Po mediáne sledovania 9.3 mesiaca vykazovalo 70 % regrutovaných pacientov pokračujúcu odozvu pri limite údajov.
White blood cell count reduction, encephalopathy, anaemia, and syndróm uvoľnenia cytokínov 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 bunková terapia.
"Táto zdatnosť T buniek by mohla byť spojená s vyššou terapeutickou účinnosťou, čo by malo za následok lepšie výsledky u pacientov," dodal Neelapu.
Po vynikajúcich priebežných výsledkoch lieku ZUMA-12 plánujú výskumníci pokračovať v sledovaní pacientov, aby sa zabezpečilo, že ich reakcie na liek budú dlhodobé.
“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-bunka lymfóm.
