Jakavi/Jakafi Ua Tau Zoo hauv Kev Kho Mob Steroid Refractory Chronic Graft-versus-host Disease (GvHD)!-2/2

REACH3 txoj kev tshawb fawb mus txog qhov kawg qhov kawg: nyob rau 24 lub lim tiam ntawm kev kho mob, piv nrog pab pawg BAT, tag nrho cov lus teb (ORR) ntawm ruxolitinib pab pawg tau zoo dua qub (49.7% vs 25.6%, p< 0.0001)="" .="" tib="" lub="" sijhawm,="" txij="" lub="" sijhawm="" twg="" los="" txog="" rau="" lub="" asthiv="" 24,="" 76.4%="" ntawm="" cov="" neeg="" mob="">ruxolitinibpab pawg ua tiav cov lus teb zoo tshaj plaws (BOR) thiab 60.4% hauv pawg BAT (LOSSIS=2.17; 95% CI: 1.34-3.52). Lub sijhawm nruab nrab ntawm cov lus teb (DOR) tsis tau mus txog hauv pab pawg Jakavi, thiab 6.24 lub hlis hauv pab pawg BAT.

Tsis tas li ntawd,ruxolitinibkuj tau qhia txog kev txheeb xyuas tseem ceeb thiab kev kho mob tseem ceeb hauv qhov kawg ntawm qhov kawg: (1) Piv nrog pab pawg BAT, pab pawg ruxolitinib tau muaj kev vam meej tsis muaj txoj sia nyob (FFS; txhais tau tias yog rov tshwm sim thaum ntxov ntawm tus kab mob thiab pib kho cov txheej txheem tshiab) Kho mob ntev GvHD, kev tuag ntawm kev tuag) pom kev txhim kho tseem ceeb (nruab nrab FFS: tsawg dua 5.7 lub hlis; HR=0.370; 95%CI: 0.268-0.510; p< 0.0001).="" (2)="" raws="" li="" qhov="" hloov="" kho="" tus="" lej="" lee="" cov="" tsos="" mob="" (mlss)="" nplai,="" qhov="" piv="" ntawm="" cov="" neeg="" teb="" uas="" nws="" cov="" qhab="" nias="" ntawm="" tus="" tsos="" mob="" (tss)="" tau="" raug="" txo="" los="" ntawm="" points7="" cov="" ntsiab="" lus="" los="" ntawm="" lub="" hauv="" paus="" tau="" siv="" los="" ntsuas.="" pab="" pawg="" ruxolitinib="" muaj="" cov="" tsos="" mob="" ntawm="" tus="" kheej="" ntau="" dua="" li="" pab="" pawg="" txhim="" kho="" bat="" (24.2%="" vs="" 11.0%;="" p="0.0011)." (3)="" kev="" tshuaj="" xyuas="" pab="" pawg="" tshiab="" pom="" tias="" tsis="" muaj="" teeb="" meem="" dab="" tsi="" ntawm="" lub="" cev="" sib="" txawv="" cuam="" tshuam="" ntawm="" lub="" hauv="" paus,="" cov="" neeg="" mob="" kho="" nrog="" ruxolitinib="" muaj="" qhov="" ua="" tau="" zoo="">

Hauv txoj kev tshawb fawb no, tsis pom cov cim qhia txog kev nyab xeeb tshiab, thiab cov xwm txheej tsis zoo (AE) suav nrog kev kho mob zoo ib yam nrog kev paub txog kev nyab xeeb ntawmruxolitinib. Cov xwm txheej tsis zoo feem ntau ntawm qib 3 lossis siab dua hauv pab pawg ruxolitinib thiab BAT yog thrombocytopenia (15.2% vs 10.1%), ntshav tsis txaus (12.7% vs 7.6%), neutropenia (8.5% vs 3.8%), thiab mob ntsws (8.5) % vs. 3.8%). % vs 9.5%). Txawm hais tias 37.6% thiab 16.5% ntawm cov neeg mob xav tau los kho qhov koob tshuaj ntawm ruxolitinib thiab BAT vim muaj cov xwm txheej tsis zoo, feem, cov neeg mob uas txiav kev kho mob txuas ntxiv vim qhov xwm txheej tsis zoo hauv ob pab pawg tau qis dua, 16.4% hauv pawg ruxolitinib thiab 7 % hauv pawg BAT Cov neeg tuag tau zoo ib yam hauv pab pawg kho mob (18.8% hauv pawg ruxolitinib thiab 16.5% hauv pab pawg BAT). Cov neeg tuag qhia los ntawm pab pawg ruxolitinib, feem ntau tshwm sim los ntawm kev mob GvHD ntev thiab/lossis nws txoj kev kho mob, siab dua me ntsis ntawm pawg BAT (13.3% vs 7.9%).

REACH3 soj ntsuam cov ntaub ntawv ntxaws ntxaws

Kev sib tsoo tiv thaiv tus kab mob tus tswv (GvHD) yog ib qho tshwm sim thiab muaj peev xwm ua rau muaj kev phom sij rau lub neej tom qab kev hloov pauv qia cell allogeneic. Nws yog qhov tshuaj tiv thaiv ntawm cov neeg pub dawb lub hlwb tawm tsam tus neeg tau txais lub cev ib txwm vim tias cov neeg pub dawb lub hlwb suav tus neeg tau txais cov cell zoo li txawv teb chaws. Ob hom tseem ceeb ntawm GvHD yog mob hnyav GvHD (tshwm sim tsis pub dhau 100 hnub tom qab hloov chaw) thiab mob hnyav GvHD (tshwm sim tsis pub dhau 100 hnub tom qab hloov chaw). Tom qab kev hloov pauv qia cell allogeneic, kwv yees li 50% ntawm cov neeg mob yuav mob hnyav lossis mob GvHD, lossis ob qho tib si. Cov tsos mob ntawm tus kab mob GvHD tuaj yeem cuam tshuam rau ntawm daim tawv nqaij, mob plab zom mov, mob siab, lub qhov ncauj, lub ntsws, thiab pob qij txha. Rau cov neeg mob uas tsis teb rau thawj qhov kev kho mob steroid lossis suav tias yog steroid-refractory, kev xaiv kho ntxiv yog xav tau sai.

Cov txiaj ntsig ntawm REACH3 txoj kev tshawb fawb yav dhau los tshaj tawm cov txiaj ntsig tau zoo ntawm theem tseem ceeb III REACH2 kev kawm ntawm Jakavi hauv kev kho mob GvHD. Qhov kawg yog thawj qib III kev kawm kom ua tiav qhov kawg ntawm qhov kawg hauv kev kho mob GvHD. Cov ntaub ntawv qhia tias: nrog kev kho tau zoo tshaj plaws Piv nrog (BAT), Jakafi tau txhim kho qhov ua tau zoo ntawm cov ntsuas ntsuas hauv cov neeg mob uas muaj cov tshuaj tiv thaiv kab mob GvHD.

Thaum lub Tsib Hlis 2019, Asmeskas FDA tau pom zoo ruxolitinib (muag los ntawm Incyte hauv Asmeskas raws li lub npe lag luam Jakafi) raws li cov txiaj ntsig ntawm ib leeg-caj dab theem II REACH1 txoj kev tshawb fawb rau kev kho mob steroid-refractory mob GvHD rau menyuam yaus thiab cov neeg laus hnub nyoog 12 xyoo thiab laus dua. . Nws tsim nyog hais tias ruxolitinib yog thawj cov tshuaj tau pom zoo los ntawm FDA los kho tshuaj steroid-refractory GvHD. Hauv REACH1 txoj kev tshawb fawb, tag nrho cov lus teb (ORR) ntawm ruxolitinib nyob rau hnub 28 ntawm kev kho mob yog 57%, thiab ua tiav cov lus teb (CR) yog 31%.

Thaum lub Plaub Hlis 2020, cov txiaj ntsig ntawm REACH2 txoj kev tshawb fawb tau luam tawm hauv New England Journal of Medicine (NEJM): Sib piv nrog pab pawg kho mob BAT, pab pawg kho mob Jakavi muaj qhov txiaj ntsig zoo dua qub (ORR) hnub 28 (62%) vs 39%, p< 0.001),="" thawj="" qhov="" kawg="" ntawm="" txoj="" kev="" tshawb="" fawb="" tau="" mus="" txog.="" hais="" txog="" cov="" ntsiab="" lus="" tseem="" ceeb="" thib="" ob,="" piv="" nrog="" pab="" pawg="" kho="" mob="" bat,="" kev="" faib="" ua="" feem="" ntawm="" cov="" neeg="" mob="" hauv="" pab="" pawg="" kho="" mob="" jakavi="" uas="" tswj="" hwm="" orr="" nyob="" ruaj="" khov="" tsis="" pub="" dhau="" 8="" lub="" lis="" piam="" tau="" zoo="" dua="" (40%="" vs="" 22%,="">< 0.001).="" ib="" qho="" ntxiv,="" qhov="" tsis="" muaj="" txoj="" sia="" nyob="" tsis="" muaj="" sia="" (ffs)="" ntawm="" pab="" pawg="" kho="" mob="" jakavi="" tau="" ntev="" dua="" li="" ntawm="" pab="" pawg="" kho="" mob="" bat="" (5.0="" hli="" vs="" 1.0="" hli;="" hr="0.46," 95%ci:="" 0.35,="" 0.60),="" thiab="" lwm="" qhov="" kawg="" qhov="" kawg="" kuj="" tau="" pom="" tias="" muaj="" kev="" hloov="" pauv="" zoo,="" suav="" nrog="" lub="" sijhawm="" zam="">

ruxolitinibyog thawj qhov ncauj Janus kinase 1 thiab Janus kinase 2 (JAK1/JAK2) inhibitor. Cov tshuaj' qhov qhia tam sim no suav nrog: pob txha fibrosis, polycythemia vera (PV), corticosteroid-refractory mob hnyav-tiv thaiv tus kab mob (GvHD). Hauv Asmeskas kev lag luam, cov tshuaj muaj npe zoo li Jakafi thiab muag los ntawm Incyte; sab nraum Teb Chaws Asmeskas, cov tshuaj muaj npe zoo li Jakavi thiab muag los ntawm Novartis.

Tam sim no, Incyte tseem tab tom tsim ruxolitinib qab zib, uas yog nyob rau theem III kev txhim kho hauv chaw kho mob: (1) rau kev kho mob ntawm cov neeg mob uas mob me me mus rau mob atopic dermatitis (TRuE-AD project), (2) rau kev kho cov hluas thiab Cov neeg laus vitiligo ( TRUE-V project). Incyte muaj txoj cai thoob ntiaj teb los tsim thiab ua lag luam ruxolitinib qab zib.

Txog kev kho mob ntawm daim tawv nqaij atopic, qhov project TRuE-AD tau ua tiav tiav nyob rau thawj ib nrab ntawm 2020. Tam sim no, Asmeskas FDA tab tom tshuaj xyuas Daim Ntawv Thov Tshuaj Tshiab (NDA) rau ruxolitinib qab zib rau kev kho mob atopic dermatitis hauv cov hluas thiab cov laus (≥12 xyoos).

Hais txog kev kho tus mob vitiligo, thaum lub Tsib Hlis xyoo no, txoj haujlwm TRuE-V tau ua tiav, thiab ob theem 3 kev tshawb fawb tau mus txog thawj qhov kawg thiab qhov tseem ceeb thib ob qhov kawg: piv nrog cov tshuaj nplaum,ruxolitinibqab zib muaj cov txiaj ntsig tseem ceeb hauv kev kho mob vitiligo -qhov tseem ceeb Nws tuaj yeem txhim kho lub ntsej muag vitiligo, txhim kho qhov txhab ntawm daim tawv nqaij thiab rov ua dua ntawm tag nrho lub cev vitiligo, thiab muaj kev nyab xeeb zoo. Raws li TRuE-V txoj haujlwm cov ntaub ntawv, Incyte npaj yuav xa daim ntawv thov kev lag luam rau ruxolitinib qab zib rau vitiligo hauv Tebchaws Meskas thiab European Union hauv ib nrab ntawm xyoo 2021. Yog pom zoo, ruxolitinib cream yuav yog thawj zaug thiab tsuas yog siv tshuaj rau kho vitiligo rau kev rov ua dua tshiab.