Iulie 25, 2021: Kite, o companie Gilead (Nasdaq: GILD), a anunțat astăzi că FDA a acordat TecartusTM (brexucabtagene autoleucel, fost KTE-X19), primul și singurul aprobat receptorul antigen himeric CAR terapia cu celule T for the treatment of adult patients with relapsed or refractory mantle cell lymphoma, accelerated approval (MCL). The FDA granted priority review and breakthrough therapy designation to this one-time therapy, which was based on the results of ZUMA-2, a single-arm, open-label study in which 87 percent of patients responded to a single infusion of Tecartus, with 62 percent achieving a complete response (CR). 18% of patients who were evaluated for safety had sindromul de eliberare de citokine (CRS) of Grade 3 or higher, and 37% had neurologic toxicities of Grade 3 or higher.
“Despite promising advances, there are still significant gaps in treatment for MCL patients who progress after initial therapy,” said Michael Wang, MD, ZUMA-2 Lead Investigator and Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center. “Many patients have high-risk disease, which means they are more likely to progress despite treatment. “Tecartus is the first cell therapy available to people with relapsed or refractory MCL. It has an impressive response rate of nearly 90% and early clinical evidence suggests that remissions may last through later lines of therapy. This makes it an important choice for these patients.”
„Suntem mândri să lansăm a doua noastră terapie celulară, deoarece Kite se angajează să aducă promisiunea Terapia CAR T to patients with haematological cancers,” said Christi Shaw, Kite’s Chief Executive Officer. “I would like to express my gratitude to the patient study participants, caregivers, clinical researchers, regulators, and dedicated Kite colleagues who contributed to this approval, and we look forward to working with the limfom community to bring this potentially transformative therapy to patients with relapsed or refractory MCL.”
Tecartus’ product label includes a boxed warning about the risks of SIR and neurologic toxicities. The FDA has approved a Risk Evaluation and Mitigation Strategy (REMS) for Tecartus, which has been combined with the REMS for Yescarta® (axicabtagene ciloleucel). The REMS programme will inform and educate healthcare professionals about the risks associated with Tecartus therapy, and training and certification in the REMS programme will be a requirement for centres offering Tecartus therapy to receive final authorization.
MCL is a rare type of limfom non-Hodgkin (NHL) that develops from cells in the lymph node’s “mantle zone” and primarily affects men over the age of 60. Following a relapse, MCL is extremely aggressive, and many patients progress after treatment.
The Lymphoma Research Foundation’s Chief Executive Officer, Meghan Gutierrez, said, “This approval marks the first CAR T cell therapy approved for mantle cell lymphoma patients and represents a new frontier in the treatment of this disease.” “Researchers have made significant progress in our understanding of this disease over the last decade, and we’ve seen an increase in patient clinical trials, which we hope will continue to improve treatment strategies and options for people with mantle cell lymphoma. Today’s news builds on that progress and gives mantle cell patients and their families reason to be hopeful.”
Kite’s commercial manufacturing facility in El Segundo, California, will produce Tecartus. Kite achieved a 96 percent manufacturing success rate in the ZUMA-2 trial, with a median manufacturing turnaround time of 15 days from leukapheresis to product delivery. Patients with advanced disease, who are severely ill and at risk of rapid progression, require manufacturing speed in particular.
Kite Konnect®, o platformă tehnologică integrată care oferă informații și asistență pe tot parcursul procesului de terapie pentru cei comercializați de Kite. terapii CAR T, including courier tracking for shipments and manufacturing status updates, is available to patients whose healthcare professionals have prescribed Tecartus therapy. Kite Konnect is a support system for patients who are receiving Yescarta or Tecartus, as well as information for the healthcare teams who are supporting them.
KTE-X19 este în prezent evaluat în Uniunea Europeană, iar Agenția Europeană pentru Medicamente i-a acordat denumirea de Medicamente prioritare (PRIME) pentru MCL recidivat sau refractar.
Rezultatele studiului Tecartus
Aprobarea Tecartus se bazează pe rezultatele studiului pivot ZUMA-2 în curs de desfășurare, care este un studiu deschis cu un singur braț. În studiu au fost înrolați 74 de pacienți adulți cu MCL recidivat sau refractar care au primit anterior chimioterapie care conține antraciclină sau bendamustină, tratament cu anticorpi anti-CD20 sau un inhibitor al tirozin kinazei Bruton (ibrutinib sau acalabrutinib). Obiectivul principal a fost rata de răspuns obiectiv (ORR), care a fost definită ca rata combinată a răspunsurilor CR și parțiale, astfel cum a fost evaluată de un Comitet Independent de Evaluare Radiologică în conformitate cu Clasificarea Lugano (2014). (IRRC).
În cadrul cercetării, 87 la sută dintre pacienți (n=60 evaluabili pentru analiza eficacității) au reacționat la o singură perfuzie cu Tecartus, 62 la sută obținând un răspuns complet. Urmărirea a fost la cel puțin șase luni după primul răspuns obiectiv al bolii pentru toți pacienții. Timpul mediu de reacție nu a fost încă determinat.
In the experiment, 18% of patients (n=82 evaluable for safety) had Grade 3 or higher CRS, while 37% of patients had neurologic problems. Anemia, neutropenia, thrombocytopenia, hypotension, hypophosphatemia, encephalopathy, leukopenia, hypoxia, pyrexia, hyponatremia, hypertension, infection-pathogen unclear, pneumonia, hypocalcemia, and lymphopenia were the most prevalent Grade 3 or higher adverse effects (10%). With a Risk Evaluation and Mitigation Strategy, the FDA approved Tecartus (REMS). The Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program has been integrated with the Tecartus REMS and is now known as the “Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program”
Despre Tecartus
Tecartus is an autologous, anti-CD19 CAR T cell therapy. Tecartus uses the XLP™ manufacturing process that includes T cell enrichment, a necessary step in certain B-cell malignancies in which circulating lymphoblasts are a common feature. In addition to MCL, Tecartus is also currently in Phase 1/2 trials in acute lymphoblastic leukemia (ALL) and leucemie limfocitară cronică (CLL). The use of Tecartus in ALL and CLL is investigational, and its safety and efficacy have not been established in these cancer types.
Indicație Tecartus
Tecartus este o imunoterapie autologă cu celule T modificată genetic, direcționată de CD19, indicată pentru tratamentul pacienților adulți cu limfom cu celule de manta (MCL) recidivat sau refractar.
Această indicație este aprobată în conformitate cu aprobarea accelerată, bazată pe rata generală de răspuns și durabilitatea răspunsului. Continuarea aprobării pentru această indicație poate fi condiționată de verificarea și descrierea beneficiului clinic într-un studiu de confirmare.
