Livtencity: Thawj cov tshuaj siv rau kev kho cov kab mob refractory CMV hauv cov neeg tau txais kev hloov pauv!--2/2

Txoj kev tshawb nrhiav TAK-620-303 yog ua tiav hauv cov neeg txais kev hloov pauv ntawm cov refractory, nrog lossis tsis muaj tshuaj tiv thaiv (R / R) cytomegalovirus (CMV) kab mob / kab mob, thiab cov tshuaj tiv thaiv kab mob TAK-620 (maribavir) yuav raug kawm. ) Thiab cov tshuaj tiv thaiv kab mob ib txwm muaj (kev kho mob los ntawm tus kws tshawb nrhiav [IAT], kev sib xyaw ntawm ib lossis ntau dua ntawm cov tshuaj hauv qab no: ganciclovir [ganciclovir], valganciclovir [valganciclovir], foscarnet [foscarnet], western Dofovir [cidofovir]) tau muab piv. . Lub ntsiab lus kawg ntawm txoj kev tshawb no yog CMV viremia clearance tus nqi tau lees paub nyob rau 8th lub lim tiam ntawm kev kho mob (kawg lub sijhawm kho), thiab qhov tseem ceeb thib ob qhov kawg yog qhov CMV tshem tawm tus nqi thiab cov tsos mob tswj tau mus rau lub lim tiam 16.

Cov txiaj ntsig ntawm txoj kev tshawb fawb los ntawm tag nrho cov neeg mus sim tau pom tias maribavir yog qhov zoo tshaj rau kev kho tshuaj tiv thaiv kab mob raws li CMV viremia clearance tus nqi ntawm lub lim tiam 8 ntawm txoj kev tshawb no. Tshwj xeeb: nyob rau hauv yim lub lim tiam ntawm txoj kev tshawb no, ntawm cov neeg tau txais kev hloov pauv uas tau txais kev kho mob antiviral, nrog lossis tsis muaj tshuaj tiv thaiv (R / R), CMV kab mob / kev kis kab mob, qhov feem pua ​​​​ntawm cov neeg mob uas tau txais kev pom zoo tshem tawm ntawm CMV viremia, Pab pawg kho mob maribavir (55.7%, n=131/235) yog ntau tshaj ob zaug ntawm pab pawg kho mob (23.9%, n=28/117) (kho qhov sib txawv [95% CI]: 32.8% [22.8-42.7]; p< 0.001; ib.

Cov ntaub ntawv ntawm pawg pab pawg soj ntsuam pom tau hais tias ntawm cov neeg tau txais kev hloov pauv tau lees paub tias yog genotype-resistant CMV kab mob ntawm qhov kev ntsuam xyuas hauv paus, qhov feem pua ​​​​ntawm cov neeg mob tau ua tiav qhov kev lees paub CMV viremia clearance ntawm lub lim tiam 8 ntawm txoj kev tshawb no (thaum kawg ntawm lub sijhawm kho. ), kho nrog maribavir Cov pab pawg (62.8%, 76/121) yog ntau tshaj 3 npaug ntawm pawg kho mob IAT (20.3%, 14/69) (kho qhov sib txawv [95% CI]: 44.1% [31.3, 56.9]).

Hauv txoj kev tshawb no, cov neeg tau txais kev hloov pauv tau kho nrog maribavir tau pom tias muaj tsawg dua ntawm kev kho mob toxicities, uas yog ib txwm muaj nyob rau hauv cov kev kho mob antiviral. Tshwj xeeb, cov neeg tau txais kev hloov pauv tau kho nrog maribavir muaj qhov tshwm sim qis dua ntawm kev kho neutropenia piv nrog cov neeg txais kev hloov pauv tau kho nrog valganciclovir / ganciclovir (1.7% [4/234] vs 25% [14/56]), piv nrog foscarnet-kho cov neeg tau txais kev cog qoob loo. , qhov xwm txheej ntawm kev kho mob ntsig txog mob raum raug mob qis dua (1.7%[4/234] vs 19.1[9/47]). Qhov tshwm sim ntawm cov xwm txheej tsis zoo (TEAE) thaum lub sij hawm txhua theem ntawm kev kho mob hauv pab pawg maribavir thiab pab pawg kho mob yog 97.4% (228/234) thiab 91.4% (106/116), feem. Feem ntau TEAEs hauv pawg maribavir yog dysgeusia (35.9%, 84/234), xeev siab (8.5%, 20/234), thiab ntuav (7.7%). Qhov tshwm sim ntawm TEAEs nyob rau hauv pab pawg maribavir thiab pab pawg kho mob ib txwm ua rau kev txiav txim siab ntawm kev tshawb fawb tshuaj yog feem ntau 13.2% (31/234) thiab 31.9% (37/116). Muaj 2 tus neeg tuag vim yog kev kho mob hnyav TAEs (1 hauv txhua pab pawg kho mob).

Cytomegalovirus (CMV) yog tus kab mob beta herpes uas feem ntau kis rau tib neeg; 40% -100% ntawm cov neeg laus muaj cov pov thawj serological ntawm tus kab mob yav dhau los. CMV feem ntau latent thiab asymptomatic nyob rau hauv lub cev, tab sis tej zaum yuav reactivated thaum immunosuppression. Cov tib neeg uas muaj kev tiv thaiv kab mob tsis zoo tuaj yeem tsim cov kab mob loj, suav nrog cov neeg mob tau txais cov tshuaj tiv thaiv kab mob cuam tshuam nrog ntau yam kev hloov pauv xws li hematopoietic cell transplantation (HCT) lossis hloov khoom nruab nrog cev (SOT). Ntawm qhov kwv yees li ntawm 200,000 tus neeg laus hloov pauv txhua xyoo, CMV yog ib qho ntawm cov kab mob kis ntau tshaj plaws hauv cov neeg tau txais kev hloov pauv. Qhov kwv yees tshwm sim hauv SOT cov neeg tau txais kev hloov pauv yog 16-56%, thiab qhov tshwm sim hauv HCT cov neeg tau txais kev hloov pauv yog 30- 70%. Hauv cov neeg tau txais kev hloov pauv, qhov rov ua haujlwm ntawm CMV tuaj yeem ua rau muaj qhov tshwm sim loj, suav nrog kev poob ntawm cov kabmob hloov pauv, thiab hauv qhov xwm txheej hnyav, nws tuaj yeem ua rau tuag taus. Cov kev kho mob uas twb muaj lawm rau kev kho tus kab mob CMV tom qab hloov pauv tuaj yeem ua rau muaj kev phiv loj heev, yuav tsum tau hloov koob tshuaj lossis tsis ua kom muaj peev xwm tiv thaiv tus kab mob rov ua dua tshiab. Tsis tas li ntawd, cov kev kho mob uas twb muaj lawm yuav xav tau lossis ncua mus pw hauv tsev kho mob vim yog kev tswj hwm.

Maribavir belongs rau ib chav kawm ntawm cov tshuaj hu ua benzimidazole nucleosides, uas tuaj yeem tsom mus rau inhibit pUL97 protein kinase ntawm CMV, yog li muaj feem cuam tshuam rau ntau yam txheej txheem tseem ceeb ntawm CMV replication, suav nrog tus kab mob DNA replication, viral gene qhia, encapsidation, thiab mature txheej lub plhaub khiav tawm. los ntawm lub nucleus ntawm tus kab mob cell.

Maribavir yog ib qho kev kho qhov ncauj bioavailable antiviral therapy tsim rau hematopoietic stem cell transplantation (HSCT) lossis cov neeg tau txais kev hloov pauv hauv nruab nrog cev (SOT) uas tau nrog los ntawm CMV kab mob thiab tiv taus los yog refractory rau tam sim no tus qauv CMV kho cov tshuaj. Hauv Tebchaws Meskas thiab European Union, maribavir tau txais kev tso cai Orphan Drug Designation (ODD) rau kev kho mob hnyav CMV viremia nyob rau hauv cov neeg mob uas muaj kev pheej hmoo siab thiab kho cov kab mob CMV hauv cov neeg mob immunocompromised. Hauv Tebchaws Meskas, maribavir kuj tau tso cai Breakthrough Drug Designation (BTD) rau cov neeg tau txais kev hloov pauv los kho cov kab mob CMV uas tiv taus lossis rov ua rau cov kev kho mob yav dhau los. Hauv Suav teb, maribavir tau txais daim ntawv tso cai pom zoo rau kev sim tshuaj nyob rau lub Plaub Hlis 2020, thiab nws cov lus qhia txog kev loj hlob yog: rau kev kho mob ntawm CMV kab mob lossis kab mob.