Julij 25, 2021: Kite, podjetje Gilead (Nasdaq: GILD), je danes objavilo, da je FDA podelila TecartusTM (brexucabtagene autoleucel, prej KTE-X19), prvega in edinega odobrenega. terapija s T-celicami receptorja himernega antigena 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 sindrom sproščanja citokinov (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.”
"Ponosni smo, da smo začeli z drugo celično terapijo, ker se Kite zavzema za obljubo CAR T terapija 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 CRS 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 je redka vrsta ne-Hodgkinov limfom (NHL), ki se razvije iz celic v "območju plašča" bezgavk in prizadene predvsem moške, starejše od 60 let. Po ponovitvi je MCL izjemno agresiven in mnogi bolniki po zdravljenju napredujejo.
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®, integrirana tehnološka platforma, ki zagotavlja informacije in pomoč v celotnem procesu zdravljenja za Kitejeve komercializirane CAR T terapije, 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 se trenutno ocenjuje v Evropski uniji, Evropska agencija za zdravila pa mu je podelila oznako Prioritetna zdravila (PRIME) za ponovitev ali neodzivno MCL.
Rezultati preskusa Tecartus
Odobritev zdravila Tecartus temelji na rezultatih tekočega ključnega preskušanja ZUMA-2, ki je odprta študija z eno samo krakom. V preskušanje je bilo vključenih 74 odraslih bolnikov z relapsom ali neodzivnim MCL, ki so predhodno prejemali kemoterapijo, ki je vsebovala antraciklin ali bendamustin, zdravljenje s protitelesi proti CD20 ali zaviralec tirozin kinaze Bruton (ibrutinib ali akalabrutinib). Primarni opazovani dogodek je bila stopnja objektivnega odziva (ORR), ki je bila opredeljena kot skupna stopnja CR in delnih odzivov, kot je ocenil neodvisni odbor za radiološki pregled v skladu z Lugansko klasifikacijo (2014). (IRRC).
V raziskavi se je 87 odstotkov bolnikov (n = 60, ocenjenih za analizo učinkovitosti) odzvalo na eno infuzijo Tecartusa, 62 odstotkov pa je doseglo popoln odziv. Spremljanje je bilo najmanj šest mesecev po prvem objektivnem odzivu na bolezen za vse bolnike. Mediani reakcijski čas še ni določen.
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 avtoleucel) REMS Program has been integrated with the Tecartus REMS and is now known as the “Yescarta (axicabtagene ciloleucel) and Tecartus (brexucabtagene autoleucel) REMS Program”
O Tecartu
Tecartus is an autologous, anti-CD19 CAR T cell therapy. Tecartus uses the XLP™ proizvodni proces, ki vključuje obogatitev s T-celicami, kar je nujen korak pri nekaterih malignostih B-celic, pri katerih so krožeči limfoblasti skupna značilnost. Poleg MCL je Tecartus trenutno tudi v preskušanjih faze 1/2 pri akutni limfoblastni levkemiji (ALL) in kronična limfocitna levkemija (CLL). The use of Tecartus in ALL and CLL is investigational, and its safety and efficacy have not been established in these cancer types.
Indikacija Tecartus
Tecartus je gensko spremenjena avtologna T-celična imunoterapija, usmerjena na CD19, indicirana za zdravljenje odraslih bolnikov z relapsom ali neodzivnim limfomom plaščnih celic (MCL).
Ta indikacija je odobrena s pospešeno odobritvijo na podlagi splošne stopnje odziva in trajnosti odziva. Nadaljnja odobritev te indikacije je lahko odvisna od preverjanja in opisa klinične koristi v potrditvenem preskušanju.
