March 2022: Sekureva kwaJohnson & Johnson, kurapwa kwakagadziridzwa nekambani pamwe newayo wekuChina-waanoshanda naye Nhoroondo ye Legend Biotech Corp kurapa rudzi rwegomarara chena reropa rakabvumidzwa neUS Food and Drug Administration.
Sarudzo yeFDA inojekesa nzira yekuti chigadzirwa chekutanga cheLegend chitenderwe muUnited States, panguva iyo agency yakawedzera kuongororwa kwayo kwemiedzo yemishonga yakaitwa kuChina. Mushonga weLegend-J&J wakatanga kuyedzwa kuChina, ndokuzopinda muUnited States neJapan.
The treatment, Carvykti/Cilta-cel, ndeyekirasi yemishonga inozivikanwa seCAR-T therapies, kana chimeric antigen receptor T-cell therapies. CAR-T medicines work by extracting and genetically modifying a patient’s own disease-fighting T-cells to target specific proteins on cancer cells, then replacing them to seek out and attack cancer.
Legend uye J&J vachatengesa mushonga muGreater China pa70-30 kupatsanurwa mupurofiti, uye mune dzimwe nyika dzese muchikamu che50-50 mupurofiti.
February 28, 2022-Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), kambani yepasi rose yebiotechnology inogadzira, inogadzira uye inoshambadzira marapirwo matsva ekurapa zvirwere zvinouraya, nhasi yazivisa kuti US Food and Drug Administration (FDA) yabvumidza chigadzirwa chayo chekutanga, CARVYKTI™(ciltacabtagene autoleucel; ciltacel), chekurapa vanhu vakuru vane myeloma yakadzokororwa kana kuti refractory multiple myeloma (RRMM) vakagamuchira mitsara mina kana kupfuura yapfuura yerapi, kusanganisira proteasome inhibitor, immunomodulatory agent, uye anti-CD38 monoclonal antibody. Legend Biotech yakapinda muchibvumirano chepasirese rezenisi uye chibvumirano chekushandira pamwe neJanssen Biotech, Inc. (Janssen) kugadzira nekutengesa ciltacel muna Zvita 2017.
CARVYKTITM inonzi chimeric antigen receptor T-cell (CAR-T) therapy ine maviri B-cell maturation antigen (BCMA) -targeting single domain.
masoja ekudzivirira chirwere uye anopiwa seanopinzwa kamwe chete ane mwero unokurudzirwa kubva pa 0.5 kusvika 1.0 x 106 CAR-positive aviable T cells pakg yehuremu hwemuviri. Muchidzidzo chakakosha cheCARTITUDE-1, mhinduro dzakadzika uye dzakasimba dzakaonekwa kune varwere vane RRMM (n = 97), vane huwandu hwepamusoro hwekupindura (ORR) hwe98 muzana (95 muzana yekuvimba nguva [CI]: 92.7-99.7) kusanganisira 78 muzana yevarwere vanowana stringent
mhinduro yakakwana (sCR, 95 muzana CI: 68.8-86.1).
1 Pakati pepakati pemwedzi ye18 kutevera, nguva yepakati yekupindura (DOR) yaiva 21.8 mwedzi (95 muzana CI 21.8-isingaenzaniswi).
1
CARVYKTI™ inowanikwa chete kuburikidza nechirongwa chakarambidzwa pasi peRisk Evaluation uye Mitigation Strategy (REMS) inonzi CARVYKTI™.
REMS Chirongwa.1 Ruzivo Rwekuchengetedza rweCARVYKTI™ runosanganisira Yambiro Yebhokisi maererano neCytokine Release Syndrome (CRS), Immune
Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism uye Guillain-Barré syndrome, hemophagocytic
lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), uye yakareba uye/kana inodzokororwa cytopenia.
1 Yambiro uye Chengetedzo
zvinosanganisira cytopenias yakarebesa uye inodzokororwa, kutapukira, hypogammaglobulinemia, hypersensitivity reactions, yechipiri malignancies uye
mhedzisiro pakukwanisa kutyaira uye kushandisa michina.
1 Maitiro akajairika akashata (≥20 muzana) ndeye pyrexia, CRS,
hypogammaglobulinemia, hypotension, marwadzo emusculoskeletal, kuneta, zvirwere-pathogen isina kutaurwa, kukosora, kupindwa nechando, manyoka, kusvotwa, encephalopathy, kuderera kwechido chekudya, hutachiona hwepamusoro, kutemwa nemusoro, tachycardia, dzungu, dyspnea, edema, mavhairasi, constipagulopathy, kurutsa.
"Multiple myeloma inoramba iri hosha isingarapike ine varwere vakanyanya kurapwa vakatarisana nekusaita fungidziro dzisina nzira dzekurapwa," akadaro Ying Huang, PhD, CEO uye CFO weLegend Biotech. "Nhasi kubvumidzwa kweCARVYKTI inguva yakakosha kuLegend Biotech nekuti ndizvo
ndiyo mvumo yedu yekutanga kushambadzira, asi chinonyanya kutifadza kugona kwemushonga kuve nzira yekurapa ine simba kune varwere vanoda nguva refu, isina kurapwa. Iyi ndiyo yekutanga yekurapa kwakawanda kwesero kwatinoronga kuunza kuvarwere sezvatiri kuenderera mberi nekufambisira mberi pombi yedu munzvimbo dzezvirwere. "
Multiple myeloma inokanganisa rudzi rwemasero machena eropa anonzi plasma masero, anowanikwa mumapfupa emapfupa.2 Ruzhinji rwevarwere
kudzoka shure mushure mekurapwa kwekutanga uye kutarisana nekufungidzira kwakashata mushure mekurapa nemakirasi matatu makuru emishonga, kusanganisira
immunomodulatory agent, proteasome inhibitor uye anti-CD38 monoclonal antibody.3,4,5
"Rwendo rwekurapa kwevazhinji vevarwere vanorarama ne-multiple myeloma inguva isingagumi yekuregererwa uye kudzoka zvakare nevarwere vashoma vanowana mhinduro yakadzama sezvavanofambira mberi kuburikidza nemitsara yekurapa," akadaro Dr. Sundar Jagannath, MBBS, Purofesa weMishonga. Hematology uye Medical Oncology paGomo reSinai, uye mukuru wechidzidzo chekuongorora. "Ichi ndicho chikonzero ndanga ndichifara zvikuru nemigumisiro kubva muongororo yeCARTITUDE-1, iyo yakaratidza kuti cilta-cel inogona kupa mhinduro dzakadzika uye dzakasimba uye kwenguva refu.
kurapwa-yemahara nguva, kunyangwe mune iyi yakanyanya pretreated akawanda myeloma murwere huwandu. Mvumo yanhasi yeCARVYKTI inobatsira kugadzirisa kudiwa kukuru kwevarwere ava.
Semushonga wakasarudzika, manejimendi eCARVYKTI™ anoda kudzidziswa kwakawanda, kugadzirira, uye chitupa kuti ive nechokwadi chechiitiko chisina musono kune varwere. Kuburikidza nemaitiro akaganhurwa, Legend naJanssen vanozomisa network inetiweki yenzvimbo dzakasimbiswa dzekurapa se
vanoshanda kuti vawedzere huwandu hwekugadzira uye kuwedzera kuwanikwa kweCARVYKTI ™ muUS yese muna 2022 nekupfuura, vachiona kuti kurapwa kweCARVYKTI ™ kunogona kupihwa kune oncologists nevarwere vavo nenzira yakavimbika uye nenguva.
Nezve CARVYKTI ™ (Ciltacabtagene autoleucel; cilta-cel) CARVYKTI™ iBCMA-inotungamirirwa, genetically modified autologous T-cell immunotherapy, iyo inosanganisira kurongazve masero eT emurwere ane transgene encoding chimeric antigen receptor (CAR) inoratidza uye kubvisa. masero anoratidza BCMA. BCMA inonyanya kuratidzwa pamusoro peakaipa akawanda myeloma B-mutsara masero, pamwe nekunonoka-danho B-masero uye plasma masero. Iyo CARVYKTI™ CAR protein ine maviri BCMA-anotarisa single domain masoja ekudzivirira ekudzivirira akagadzirirwa kupa hutsinye hwakanyanya kurwisa BCMA yemunhu. Pakusunga ku
BCMA-inoratidza masero, iyo CAR inokurudzira T-cell activation, kuwedzera, uye kubviswa kwechinangwa chemasero.
Muna Zvita 2017, Legend Biotech Corporation yakapinda muchibvumirano cherezenisi chepasi rose uye chibvumirano chekushandira pamwe neJanssen Biotech, Inc. kugadzira nekutengesa cilta-cel.
Muna Kubvumbi 2021, Legend akazivisa kuendesa kweKushambadzira Chikumbiro cheKushambadzira kuEuropean Medicines Agency ichitsvaga mvumo yecilta-cel yekurapwa kwevarwere vane kudzokazve uye/kana refractory multiple myeloma. Pamusoro peUS Breakthrough Therapy Designation yakapihwa muna Zvita 2019, cilta-cel yakagamuchira Breakthrough Therapy Designation muChina muna Nyamavhuvhu 2020. Cilta-cel akagamuchirawo Orphan Drug Designation kubva kuUS FDA muna Kukadzi 2019, uye kubva kuEuropean Commission muna Kukadzi 2020. .
NezveChidzidzo cheCARTITUDE-1
CARTITUDE-1 (NCT03548207) inoenderera mberi Phase 1b/2, yakavhurika-label, ruoko rumwechete, multi-center bvunzo inoongorora cilta-cel yekurapwa kwevarwere vakura vane kudzokazve kana kuti refractory multiple myeloma, avo vakambogamuchira mitsara mitatu yapfuura. yekurapa inosanganisira proteasome inhibitor (PI), an immunomodulatory agent (IMiD) uye anti-CD38 monoclonal antibody. Pakati pevarwere makumi mapfumbamwe nevanomwe vakanyoresa
muyedzo, 99 muzana yairamba kumutsara wekupedzisira wekurapa uye 88 muzana yaive katatu-kirasi refractory, zvichireva kuti cancer yavo haina kupindura, kana kuti haichapinduri, kune IMiD, PI uye anti-CD38 monoclonal antibody.1
Kushanda kwenguva refu uye kuchengetedza chimiro checilta-cel chiri kuongororwa muchidzidzo chirikuenderera mberi cheCARTITUDE-1, nemhedzisiro yemakore maviri yekutevera ichangobva kuratidzwa paASH 2021.6
Nezve Multiple Myeloma
Multiple myeloma igomarara reropa risingarapike rinotanga mumwongo uye rinoonekwa nekuwanda kwakanyanya kwemasero eplasma.
Muna 2022, zvinofungidzirwa kuti vanhu vanopfuura zviuru makumi matatu nevana vachabatwa nemultiple myeloma, uye vanhu vanopfuura zviuru gumi nezviviri
kufa nechirwere muUS
7 Nepo vamwe varwere vane multiple myeloma vasina zviratidzo zvachose, varwere vazhinji vanoonekwa nekuda kwe
zviratidzo zvinogona kusanganisira matambudziko emapfupa, kuderera kweropa, kukwidziridzwa kwe calcium, matambudziko etsvo kana zvirwere.
8 Kunyangwe kurapwa kuchigona
kuguma nekuregererwa, zvinosuruvarisa, varwere vangangotanga kudzoka zvakare.
3 Varwere vanotangazve mushure mekurapwa nemishonga yakajairika, inosanganisira protease inhibitors, immunomodulatory agents, uye anti-CD38 monoclonal antibody, vane fungidziro dzisina kunaka uye nzira shoma dzekurapa dziripo.
CARVYKTI ™ Yakakosha Ruzivo Rwekuchengetedza ZVIRATIDZO NEKUSHANDISA
CARVYKTI ™ (ciltacabtagene autoleucel) inonzi B-cell maturation antigen (BCMA) -inotungamirirwa genetically modified autologous T cell immunotherapy inoratidzwa kuitira kurapwa kwevarwere vakura vane kudzokazve kana kuti refractory multiple myeloma, mushure memitsetse mina kana kupfuura yapfuura yerapi, kusanganisira proteasome. inhibitor, immunomodulatory agent, uye anti-CD38 monoclonal antibody.
YAVERA: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, uye YARERERERA uye ZVINOITIKA.
CYTOPENIA
• Cytokine Release Syndrome (CRS), kusanganisira kuuraya kana kutyisa upenyu, yakaitika muvarwere vanotevera kurapwa.
CARVYKTI™. Usapinze CARVYKTI ™ kune varwere vane hutachiona hunoshanda kana kusagadzikana kwekuzvimba. Rapa zvakanyanya kana kuuraya CRS ne tocilizumab kana tocilizumab uye corticosteroids.
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), inogona kuuraya kana kuisa upenyu munjodzi, yakaitika zvichitevera.
kurapwa neCARVYKTI ™, kusanganisira isati yatanga CRS, panguva imwe chete neCRS, mushure mekugadziriswa kweCRS, kana kusavapo kweCRS. Tarisa uone zviitiko zveurological mushure mekurapwa neCARVYKTI™. Ipa rubatsiro rwekutsigira uye / kana corticosteroids sezvinodiwa.
• Parkinsonism uye Guillain-Barré syndrome uye zvinetso zvawo zvinoguma nekuuraya kana kuisa upenyu munjodzi
zvakaitika zvichitevera kurapwa neCARVYKTI™.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), kusanganisira maitiro anouraya uye anotyisidzira upenyu,
zvakaitika kune varwere vanotevera kurapwa neCARVYKTI™. HLH/MAS inogona kuitika neCRS kana neurologic toxicities.
• Kurebesa uye/kana kudzokororwa cytopenias nekubuda ropa uye utachiona uye zvinodiwa kuti stem cell transplantation yehematopoietic.
kupora kwakaitika zvichitevera kurapwa neCARVYKTI™.
• CARVYKTI™ inowanikwa chete kuburikidza nechirongwa chakaganhurirwa pasi peRisk Evaluation and Mitigation Strategy (REMS) inonzi CARVYKTI™ REMS Program.
YAMBIRO NEZVOZVO
Cytokine Release Syndrome (CRS) kusanganisira kuuraya kana kutyisa upenyu, kwakaitika mushure mekurapa neCARVYKTI ™ mu95% (92/97) yevarwere vanogamuchira ciltacabtagene autoleucel. Giredhi 3 kana yepamusoro CRS (2019 ASTCT giredhi) 1 yakaitika mu5% (5/97) yevarwere, neGiredhi 5 CRS yakashumwa mune 1 murwere. Nguva yepakati pekutanga kweCRS yaive mazuva manomwe (renji: 7-1 mazuva). Kunyanya kuratidzwa kweCRS kwaisanganisira pyrexia (12%), hypotension (100%), yakawedzera aspartate aminotransferase (AST) (43%), chills (22%), yakawedzera alanine aminotransferase (15%) uye sinus tachycardia (14%). . Giredhi 11 kana zviitiko zvepamusoro zvakabatana neCRS zvaisanganisira kuwedzera AST uye ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, kutadza kufema, kukuvara kwakanyanya kweitsvo, kuparadzira intravascular.
coagulation, HLH/MAS, angina pectoris, supraventricular uye ventricular tachycardia, malaise, myalgias, yakawedzera C-reactive protein, ferritin, ropa alkaline phosphatase uye gamma-glutamyl transferase.
Ziva CRS zvichienderana nekiriniki mharidzo. Ongorora uye kurapa zvimwe zvikonzero zvefivha, hypoxia, uye hypotension. CRS inonzi yakabatana nezvakawanikwa zveHLH/MAS, uye physiology yemasyndromes inogona kupindirana. HLH/MAS inogona kuisa hupenyu panjodzi
mamiriro. Muvarwere vane zviratidzo zvinofambira mberi zveCRS kana refractory CRS kunyangwe kurapwa, ongorora humbowo hweHLH/MAS. Makumi matanhatu nevapfumbamwe ve97 (71%) varwere vakagamuchira tocilizumab uye/kana corticosteroid yeCRS mushure mekuisirwa ciltacabtagene autoleucel. Makumi mana nemana
(45%) varwere vakagamuchira tocilizumab chete, avo 33 (34%) vakagamuchira chirwere chimwe chete uye 11 (11%) vakagamuchira inopfuura imwe yero; Varwere ve24 (25%) vakagamuchira tocilizumab uye corticosteroid, uye murwere mumwe (1%) akagamuchira corticosteroids chete. Ita shuwa kuti madosi maviri etocilizumab anowanikwa isati yaiswa CARVYKTI™.
Tarisa varwere zuva nezuva kwemazuva gumi uchitevera CARVYKTI ™ infusion panzvimbo yehutano yakasimbiswa yeREMS yezviratidzo nezviratidzo zveCRS. Tarisa varwere kune zviratidzo kana zviratidzo zveCRS kweinenge mavhiki mana mushure mekunyudzwa. Pachiratidzo chekutanga cheCRS, pakarepo tanga kurapwa nerutsigiro rwekutarisira, tocilizumab, kana tocilizumab uye corticosteroids. Raudzira varwere kuti vatsvage kurapwa nekukurumidza kana zviratidzo kana zviratidzo zveCRS zvikaitika chero nguva. Neurologic toxicities, iyo inogona kuva yakaoma, inouraya kana kuuraya, yakaitika mushure mekurapwa neCARVYKTI™. Neurologic toxicities yaisanganisira ICANS, neurologic toxicity ine zviratidzo uye zviratidzo zveparkinsonism, Guillain-Barré Syndrome, peripheral neuropathies, uye cranial nerve palsies. Rayirira varwere pane zviratidzo uye zviratidzo zveiyi neurologic toxicity, uye pane kunonoka hunhu hwekutanga kwe
dzimwe toxicities izvi. Raira varwere kuti vatsvage kurapwa nekukurumidza kuti vawedzere kuongororwa uye manejimendi kana zviratidzo kana zviratidzo zveimwe yeiyi neurologic toxicity zvikaitika chero nguva.
Kakawanda, imwe kana kupfuura subtypes yeurologic toxicity inotsanangurwa pazasi yakaitika zvichitevera ciltacabtagene autoleucel mu26% (25/97) yevarwere, iyo 11% (11/97) yevarwere vakawana Giredhi 3 kana zviitiko zvepamusoro. Aya ma subtypes eeurologic toxicities akaonekwawo muzvidzidzo zviviri zvirikuenderera mberi.
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): ICANS yakaitika mu23% (22/97) yevarwere vanogamuchira ciltacabtagene autoleucel kusanganisira Giredhi 3 kana 4 zviitiko mu3% (3/97) uye Giredhi 5 (inouraya) zviitiko mu2%. (2/97). Nguva yepakati pekutanga kweICANS yaive mazuva masere (renji 8-1 mazuva). Vese varwere makumi maviri nevaviri vane ICANS vaive neCRS. Iyo yakajairika (≥28%) kuratidzwa kweICANS kwaisanganisira encephalopathy
(23%), aphasia (8%) uye musoro (6%). Motarisisa varwere zuva nezuva kwemazuva gumi uchitevera CARVYKTI™ kuisirwa panzvimbo yehutano yakasimbiswa yeREMS yezviratidzo nezviratidzo zveICANS. Rega zvimwe zvikonzero zveICANS zviratidzo. Tarisa varwere kune zviratidzo kana zviratidzo zveICANS kweinenge mavhiki mana mushure mekuisirwa uye kurapa nekukurumidza. Neurologic toxicity inofanira kutarisirwa nerutsigiro rwekuchengetedza uye / kana corticosteroids sezvinodiwa.
Parkinsonism: Pavarwere makumi maviri nevashanu vari muCARTITUDE-25 kudzidza vachiona chero neurotoxicity, varwere vashanu vechirume vaive neurological toxicity ine akati wandei zviratidzo uye zviratidzo zveparkinsonism, zvakasiyana neimmune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic
toxicity ne parkinsonism yakashumwa mune mamwe maedzo anoenderera mberi e ciltacabtagene autoleucel. Varwere vaive nezviratidzo zveparkinsonian uye zvisiri zveparkinsonian zvaisanganisira kubvunda, bradykinesia, kufamba kusingaite, stereotypy, kurasikirwa nekufamba kwega, kumeso kwakavharika, kusava nehanya, flat impact, kuneta, kuoma, psychomotor retardation, micrographia, dysgraphia, apraxia, kushushikana, kupererwa
kurasikirwa nepfungwa, kunonoka kuona, hyperreflexia, kurasikirwa nendangariro, kutadza kumedza, kusaita ura, kudonha, kumira akakotama, kufamba-famba, kushaya simba kwetsandanyama uye kupera, kusashanda zvakanaka kwemota, kutadza kwemota, kurasikirwa nekunzwa, akinetic mutism, uye kuburitsa zviratidzo zvemberi.
Iyo yepakati pekutanga kwe parkinsonism muvarwere ve5 muCARTITUDE-1 yaive mazuva makumi mana nematatu (rengere 43-15) kubva pakuiswa kwe ciltacabtagene autoleucel.
Tarisa varwere kune zviratidzo uye zviratidzo zve parkinsonism zvinogona kunonoka kutanga uye kutungamirirwa nematanho ekuchengeta anotsigira.
Pane ruzivo rushoma rwekushanda nemishonga inoshandiswa kurapa chirwere cheParkinson, kugadzirisa kana kugadzirisa
parkinsonism zviratidzo zvinotevera CARVYKTI ™ kurapwa.
Guillain-Barré Syndrome: Mhedzisiro inouraya inotevera Guillain-Barré Syndrome (GBS) yakaitika mune imwe ongororo inoenderera.
ciltacabtagene autoleucel kunyangwe kurapwa neintravenous immunoglobulins. Zviratidzo zvinoshumwa zvinosanganisira izvo zvinoenderana neMillerFisher musiyano weGBS, encephalopathy, kushaya simba kwemota, kukanganisa kutaura uye polyradiculoneuritis.
Monitor yeGBS. Ongorora varwere vanouya neperipheral neuropathy yeGBS. Funga kurapwa kweGBS nematanho ekuchengeta anotsigira uye pamwe chete nemaimmunoglobulins uye plasma exchange, zvichienderana nekuoma kweGBS.
Peripheral Neuropathy: Vatanhatu varwere muCARTITUDE-1 vakagadzira peripheral neuropathy. Aya ma neuropathies anoratidzwa semanzwiro, mota kana sensorimotor neuropathies. Nguva yeMedhia yekutanga kwezviratidzo yaiva mazuva 62 (mazuva 4-136), nguva yepakati yeperipheral neuropathies yaiva mazuva 256 (mazuva 2-465) kusanganisira avo vane chirwere chinoramba chichienderera mberi. Varwere vakawana peripheral neuropathy vakawanawo cranial nerve palsies kana GBS mune mimwe miedzo inoenderera ye ciltacabtagene autoleucel.
Cranial Nerve Palsies: Varwere vatatu (3.1%) vakawana cranial nerve palsies muCARTITUDE-1. Vese varwere vatatu vaive ne7th cranial nerve
palsy; mumwe murwere aive ne5th cranial nerve palsy zvakare. Nguva yeMedhia yekutanga yaive mazuva makumi maviri nematanhatu (mazuva 26-21) zvichitevera kuisirwa kwe
ciltacabtagene autoleucel. Kuitika kwe3rd uye 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, kuwedzera kwecranial nerve palsy mushure mekuvandudzwa, uye kuitika kweperipheral neuropathy muvarwere vane cranial nerve palsy zvakashumwawo mumiedzo inoenderera mberi.
ye ciltacabtagene autoleucel. Tarisa varwere kune zviratidzo uye zviratidzo zvecranial nerve palsies. Funga manejimendi ne systemic corticosteroids, zvichienderana nekuoma uye kufambira mberi kwezviratidzo nezviratidzo. Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS: Inouraya HLH yakaitika mune mumwe murwere (1%), 99
mazuva mushure me ciltacabtagene autoleucel. Chiitiko cheHLH chakatangirwa neCRS yakagara mazuva makumi mapfumbamwe nemanomwe. Kuratidzwa kweHLH/MAS
zvinosanganisira hypotension, hypoxia ine diffuse alveolar kukuvara, coagulopathy, cytopenia, uye akawanda-organ dysfunction, kusanganisira renal kusashanda zvakanaka. HLH idambudziko rinotyisa uye rine huwandu hwevanhu vanofa zvakanyanya kana ikasazivikanwa nekurapwa nekukurumidza. Kurapa kweHLH/MAS kunofanirwa kupihwa maererano nemasangano. CARVYKTI™ REMS: Nekuda kwenjodzi yeCRS uye neurologic toxicities, CARVYKTI™ inowanikwa chete kuburikidza nechirongwa chakarambidzwa pasi peRisk Evaluation uye Mitigation Strategy (REMS) inonzi CARVYKTI™ REMS.
Rumwe ruzivo runowanikwa pa www.CARVYKTIrems.com kana 1-844-672-0067.
Cytopenias Yakareba uye Yakadzokororwa: Varwere vanogona kuratidza cytopenias yakareba uye yakadzokororwa inotevera lymphodepleting chemotherapy uye CARVYKTI ™ infusion. Mumwe murwere akawana autologous stem cell therapy ye hematopoietic reconstitution nekuda kwekugara kwenguva refu thrombocytopenia.
MuCARTITUDE-1, 30% (29/97) yevarwere vakawana kwenguva yakareba Giredhi 3 kana 4 neutropenia uye 41% (40/97) yevarwere vakawana kwenguva yakareba Giredhi 3 kana 4 thrombocytopenia iyo yakanga isati yagadziriswa neZuva 30 ichitevera ciltacabtagene autoleucel infusion.
Recurrent Grade 3 kana 4 neutropenia, thrombocytopenia, lymphopenia uye anemia zvakaonekwa mu 63% (61/97), 18% (17/97), 60% (58/97),
uye 37% (36/97) mushure mekupora kubva kuGiredhi rekutanga 3 kana 4 cytopenia inotevera kuisirwa. Mushure meZuva rechi60 rinotevera ciltacabtagene autoleucel
infusion, 31%, 12% uye 6% yevarwere vaiva kudzokorora Grade 3 kana yepamusoro lymphopenia, neutropenia uye thrombocytopenia, ukuwo, pashure pokutanga kupora kwavo Grade 3 kana 4 cytopenia. Makumi masere nenomwe muzana (84/97) evarwere vaive nemumwe, vaviri, kana vatatu kana kupfuura
kudzokorora kweGiredhi 3 kana 4 cytopenias mushure mekutanga kupora kweGrade 3 kana 4 cytopenia. Vatanhatu uye 11 varwere vaiva neGiredhi 3 kana 4 neutropenia uye thrombocytopenia, maererano, panguva yekufa.
Chengetedza kuverenga kweropa pamberi uye mushure meCARVYKTI™ infusion. Tonga cytopenias nekukura zvinhu uye tsigiro yekuwedzerwa ropa chigadzirwa zvinoenderana nenharaunda yenzvimbo nhungamiro.
Zvirwere: CARVYKTI ™ haifaniri kupiwa kune varwere vane utachiona hunoshanda kana zvirwere zvinopisa. Zvirwere zvakakomba, zvinouraya kana zvinouraya zvakaitika muvarwere mushure meCARVYKTI™ infusion.
Utachiona (magiredhi ese) akaitika mu57 (59%) varwere. Zvirwere zveGrade 3 kana 4 zvakaitika muchikamu che23% (22/97) chevarwere; Zvirwere zveGiredhi 3 kana 4 zvine hutachiona husina kutaurwa hwakaitika mu17%, hutachiona hwehutachiona mu7%, hutachiona hwehutachiona mu1%, uye fungal hutachiona mu1% yevarwere.
Pakazere, varwere vana vaive nezvirwere zveGrade 5: abscess yemapapu (n=1), sepsis (n=2) nemabayo (n=1).
Tarisa varwere kune zviratidzo uye zviratidzo zvehutachiona pamberi uye shure kweCARVYKTI ™ kuiswa uye kubata varwere zvakakodzera. Gadzira prophylactic, pre-emptive uye / kana kurapa antimicrobials maererano neyakajairwa masangano nhungamiro. Febrile neutropenia yaive
yakacherechedzwa mu10% yevarwere mushure mekuti ciltacabtagene autoleucel infusion, uye inogona kunge yakafanana neCRS. Muchiitiko chefebrile neutropenia, ongorora hutachiona uye gadzirisa ne-broad-spectrum antibiotics, zvinwiwa uye kumwe kutarisira kunotsigira, sezvinoratidzwa nemishonga.
Viral Reactivation: Hepatitis B virus (HBV) reactivation, mune dzimwe nguva inokonzera fulminant hepatitis, hepatic kukundikana uye kufa, inogona kuitika kune varwere vane hypogammaglobulinemia. Ita kuongororwa kweCytomegalovirus (CMV), HBV, hepatitis C virus (HCV), uye hutachiwana hwehutachiona hwehutachiona (HIV), kana chero humwe hutachiwana hunotapukira kana hunoratidzwa nekliniki maererano nemitemo yekiriniki isati yaunganidzwa masero ekugadzira. Funga nezve antiviral therapy kudzivirira hutachiwana reactivation pamagariro enzvimbo / maitiro ekiriniki.
Hypogammaglobulinemia yakashumwa sechiitiko chakaipa mu12% (12/97) yevarwere; murabhoritari IgG mazinga akawira pasi pe500 mg/dL mushure mekuisirwa mu92% (89/97) yevarwere. Tarisa mazinga e immunoglobulin mushure mekurapwa neCARVYKTI ™ uye tonga IVIG yeIgG.
<400 mg/dL. Tonga pazvimiro zvenzvimbo, kusanganisira kudzivirira kutapukira uye mishonga inorwisa mabhakitiriya kana antiviral prophylaxis.
Kushandisa Majekiseni Aripo: Kuchengetedzeka kwekubaiwa nemishonga yekudzivirira utachiona mhenyu panguva kana kutevera CARVYKTI™ kurapwa hakuna kuongororwa.
Kudzivirira nemishonga yekudzivirira yehutachiona haikurudzirwi kwemavhiki matanhatu isati yatanga lymphodepleting chemotherapy, panguva yeCARVYKTI ™ kurapwa, uye kusvika kupora kwekudzivirira mushure mekurapwa neCARVYKTI™.
Hypersensitivity Reactions yakaitika mu5% (5/97) yevarwere vanotevera ciltacabtagene autoleucel infusion. Serious hypersensitivity reactions, kusanganisira anaphylaxis, inogona kunge yakakonzerwa nedimethyl sulfoxide (DMSO) muCARVYKTI™. Varwere vanofanira kunyatsotariswa kwemaawa maviri mushure mokupinza zviratidzo uye zviratidzo zvekunyanya kuita. Bata nekukasira uye gadzirisa zvakakodzera zvichienderana nekuoma kwe hypersensitivity reaction.
Secondary Malignancies: Varwere vanogona kutanga zvirwere zvechipiri. Chengetedza hupenyu hurefu hwechipiri chechirwere. Kana pakaitika chirwere chechipiri, bata Janssen Biotech, Inc., panhamba dzinoti 1-800-526-7736 kuti utaure uye uwane mirairo yekuunganidza.
sampuli dzevarwere dzekuongororwa kwechipiri chechirwere cheT cell yakabva.
Mhedzisiro Pakugona Kutyaira uye Kushandisa Machina: Nekuda kwekugona kwezviitiko zveurologic, zvinosanganisira kuchinjika chimiro chepfungwa, kubatwa, neurocognitive kuderera, kana neuropathy, varwere vari panjodzi yekushandurwa kana kuderera kwekuziva kana kurongeka mumavhiki e8 anotevera.
CARVYKTI™ infusion. Rairira varwere kuti varambe kutyaira uye kuita mabasa ane njodzi, sekushandisa michina inorema kana inogona kuva nengozi panguva ino yekutanga, uye kana pakaitika kutsva kwechero neurologic toxicity.
ZVAKAITIKA ZVAKAITIKA
Izvo zvinowanzoitika zvisiri zverabhoritari zvakaipa (zviitiko zvinopfuura 20%) pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal kurwadziwa, kuneta, utachiona hwehutachiona husina kutaurwa, kukosora, kupindwa nechando, manyoka, kusvotwa, encephaliteopathy, kuderera kwe appetite. chirwere chekufema, kutemwa nemusoro, tachycardia, dzungu, dyspnea, edema, hutachiona hwehutachiona, coagulopathy, kuvimbiswa, uye kurutsa. Kusawirirana kwakanyanya murabhoritari (chiitiko chikuru kupfuura kana kuenzana ne50%) zvinosanganisira thrombocytopenia, neutropenia, anemia, aminotransferase elevation, uye hypoalbuminemia.
tapota verenga Ruzivo rwakazara rweKuraira kusanganisira Bhokisi Yambiro yeCARVYKTI™.
