Roche / AbbVie Venclexta + Azacitidine Theem III: Qhov tseem ceeb tshaj tawm lub sijhawm muaj sia nyob tag nrho!

AbbVie tsis ntev los no tshaj tawm tias cov txiaj ntsig ntawm Theem III VIALE-A txoj kev tshawb nrhiav (NCT02993523) ntsuas cov tshuaj anticancer Venclexta / Venclyxto (venetoclax) rau thawj kab kev kho mob ntawm tus mob myeloid leukemia (AML) tau luam tawm online hauv New England Journal of Tshuaj ntsaws (NEJM). Txoj kev tshawb no tau ua rau cov neeg mob AML tshiab uas tsis tau txais kev kho mob, tsis tuaj yeem tiv thaiv kev kho mob ib txwm muaj, thiab piv cov placebo + azacitidine (AZA, hypomethylating tus neeg sawv cev) regimen thiab venetoclax + azacitidine regimen. Qhov ua tau zoo thiab kev nyab xeeb. Cov txiaj ntsig pom tau hais tias piv nrog cov placebo + azacitidine, venetoclax + azacitidine regimen tseem ceeb rau lub sijhawm muaj sia nyob ntev (OS). Txog NEJM tsab xov xwm, saib: Azacitidine thiab Venetoclax hauv Cov Txheej Txheem Tsis Kho Mob Myeloid Mob Ntshav Qab Zib.

Venclexta / Venclyxto yog thawj-ntawm-zoo, qhov ncauj, xaiv B-cell lymphoma factor-2 (BCL-2) inhibitor, tsim los ntawm AbbVie thiab Roche, uas koom ua ke rau kev ua lag luam ntawm Asmeskas kev lag luam (npe lag luam : Venclexta), AbbVie yog lub luag haujlwm rau kev ua lag luam ntawm kev ua lag luam sab nraud Tebchaws Asmeskas (npe lag luam: Venclyxto).

Tus thawj coj tshawb fawb ntawm VIALE-A txoj kev tshawb nrhiav thiab Dr. Courtney D. DiNardo ntawm University of Texas MD Anderson Cancer Center tau hais txog cov txiaj ntsig ntawm txoj kev tshawb fawb no: "Venetoclax + azacitidine regimen muaj txiaj ntsig zoo rau cov neeg mob AML tshiab. uas tsis tuaj yeem tiv cov kev siv tshuaj kho mob ntau ntxiv. Lub peev xwm txhawm rau txhim kho kev txheeb xyuas nruab nrab yog qhov kev nce qib loj hauv kev kho mob ntawm AML uas muaj peev xwm hloov pauv kev coj ua."

Hauv VIALE-Ib txoj kev tshawb nrhiav, tag nrho cov kev muaj sia nyob (OS) yog lub hauv paus tsuas yog qhov kawg ntawm Tebchaws Meskas, thiab OS thiab kev sib xyaw ua tiav cov lus teb tiav (CR + CRi) yog cov kev sib koom ua tiav ntawm Suav, Nyiv, European Union (EU) thiab EU siv cov tebchaws. CR + CRi qhia txog cov qhab nia ntawm kev zam tag nrho (CR) thiab kev kho tag nrog kev rov ua kom zoo tsis txaus (CRi).

Cov txiaj ntsig tau pom tias: (1) Piv nrog cov azacitidine + cov placebo pawg, Venetoclax + azacitidine kho pawg muaj lub sijhawm ntev dua OS (nruab nrab OS: 14.7 lub hlis vs 9.6 lub hlis) thiab 34% txo hauv kev pheej hmoo tuag (HR=0.66; 95% CI: 0.52-0.85; p< 0.001).="" (2)="" piv="" nrog="" pab="" pawg="" azacitidine="" +="" placebo="" pawg,="" qhov="" sib="" koom="" ua="" tiav="" kev="" sib="" cais="" tus="" nqi="" (cr="" +="" cri)="" ntawm="" venetoclax="" +="" pawg="" kho="" mob="" azacitidine="" tau="" ntau="" tshaj="" ob="" npaug="" (66.4%="" vs="" 28.3%="" ,="">< 0.001).="" tsis="" tas="" li="" ntawd,="" txoj="" kev="" tshawb="" no="" kuj="" tau="" mus="" txog="" theem="" nrab="" qhov="" kawg="" ntawm="" cr="" +="" crh="" (kev="" kho="" kom="" tiav="" +="" kev="" kho="" tiav="" nrog="" kev="" rov="" zoo="" ib="" feem):="" 64.7%="" cr="" +="" crh="" hauv="" lub="" venetoclax="" {{31}="" }="" azacitidine="" kho="" pab="" pawg,="" thiab="" 22.8="" hauv="" azacitidine="" +="" placebo="">

Hauv qhov kev tshawb fawb no, kev nyab xeeb ntawm cov tshuaj venetoclax + azacitidine regimen tau zoo ib yam nrog kev paub txog kev nyab xeeb ntawm cov tshuaj hauv cov tshuaj, thiab tsis muaj cov cim qhia txog kev nyab xeeb tsis txaus ntseeg ntsig txog qhov tseeb pom tau pom. Hauv cov kab mob venetoclax + azacitidine kho pawg, qhov tshwm sim tsis zoo tshaj plaws (tshwm sim ≥40%) feem ntau yog hematology thiab mob plab, nrog rau thrombocytopenia (46%), xeev siab (44%), thiab cem quav (43%)) , neutropenia (42%), neutropenia (42%) thiab zawv plab (41%). Ntawm cov neeg mob kho nrog venetoclax + azacitidine, feem ntau cov kev tsis haum loj (AR, tshwm sim hauv ntau dua 10% ntawm cov neeg mob) yog febrile neutropenia (30%) thiab mob ntsws (17%). Peb tus neeg mob hauv pawg venetoclax + azacitidine pawg qhia txog mob qog mob leeg mob (TLS) thaum tawm tsam, thiab tsis muaj ib pawg neeg azacitidine + pab pawg. Tag nrho cov no yog kev hloov pauv biochemical luv, uas tau daws teeb meem los ntawm cov tshuaj uas txhawb nqa uric acid excretion thiab calcium ntxiv, tsis ua rau cuam tshuam kev kho mob.

Mob myeloid mob ntshav sib luag (AML) yog ib tus neeg mob hnyav tshaj plaws thiab tsis yooj yim kho mob qog ntshav, muaj ib qhov muaj sia nyob tsawg thiab muaj kev kho kev xaiv tsawg. AML yog tsim los ntawm cov hlwb pob txha, ua rau muaj ntau ntxiv ntawm cov qe ntshav dawb hauv cov ntshav thiab cov hlwb pob txha. AML feem ntau deteriorates sai sai, tab sis tsis yog txhua tus neeg mob tsim nyog rau kev siv tshuaj kho mob ntau ntxiv. Lub hnub nyoog thiab comorbidities yog cov yam tseem ceeb uas txwv tsis pub muaj kev kho mob siab. Tsuas yog li ntawm 28% ntawm cov neeg mob tuaj yeem nyob ntev dua 5 xyoos ntev dua.

Hauv Tebchaws Meskas, Venclexta yav dhau los tau txais kev pom zoo nrawm, ua ke nrog tus neeg sawv cev hypomethylation (azacitidine [AZA] lossis decitabine [decitabine, DAC]) lossis qis cytarabine (LD-AC), kev kho mob thawj zaug ntawm cov neeg laus tshiab cov neeg mob nrog hom 2 AML, tshwj xeeb: (1) tus neeg laus AML hnub nyoog 75 xyoo thiab siab dua; (2) AML cov neeg laus cov neeg mob uas tsis haum rau kev siv tshuaj kho mob kom ntau vim kev sib txuam ntawm lwm yam kabmob.

Cov txiaj ntsig ntawm VIALE-Kev tshawb fawb tau tshaj tawm ntawm 25th European Hematology Association (EHA) Virtual Conference. AbbVie koom tes nrog Roche thiab tau xa cov txiaj ntsig ntawm VIALE-A thiab VIALE-C cov kev tshawb fawb, cov ntaub ntawv zaum kawg ntawm theem I / II kev tshawb fawb M14-358 thiab M14-387 mus rau Asmeskas FDA, nrog lub hom phiaj ntawm kev sib xyaw Venclexta nrog qis methyl Kev kho thawj kab thawj cov AML (azacitidine los yog decitabine lossis LD-AC) tau hloov pauv mus rau kev pom zoo tag nrho.

Cov tshuaj ua haujlwm ntawm cov tshuaj nquag ntawm Venclexta / Venclyxto yog venetoclax, uas yog lub qhov ncauj B-cell lymphoma factor-2 (BCL-2) inhibitor. BCL-2 protein ua lub luag haujlwm tseem ceeb hauv apoptosis (muaj kab mob ntawm tes tuag). Tiv thaiv apoptosis ntawm qee lub hlwb (suav nrog lymphocytes), thiab mob siab rau qee yam mob qog nqaij hlav, uas cuam tshuam txog kev tsim cov tshuaj tiv thaiv. Venetoclax lub hom phiaj ua rau xaiv tshwj xeeb rau kev ua haujlwm ntawm BCL-2, rov kho lub xovtooj ntawm kev sib txuas lus ntawm tes, thiab tso cai rau cov kabmob kheesxaws tua lawv tus kheej, ua tiav lub hom phiaj ntawm kev kho qog. Txog rau tam sim no, venetoclax tau txais kev pom zoo rau kev lag luam hauv ntau lub teb chaws thoob plaws ntiaj teb rau kev kho mob lymphocytic leukemia (CLL), mob cell me lymphoma (SLL), thiab mob myeloid leukemia (AML) hauv cov neeg laus.

Hauv Tebchaws Meskas, cov tshuaj venetoclax tau tso cai rau 5 kev tsim nyog cov tshuaj sib cais (BTD) los ntawm FDA: 1 BTD tau tso cai rau kev kho kab mob thawj zaug ntawm CLL, 2 BTDs tau tso cai rau kev kho mob lossis rov ua haujlwm rau CLL, thiab 2 BTDs tau tso cai kho thawj cov kab mob rau AML. Tam sim no, Roche thiab AbbVie tab tom ua ib qhov kev kho mob loj los tshawb nrhiav kev kho kab mob venetoclax monotherapy thiab kev kho mob sib xyaw rau ntau hom mob qog ntshav, nrog rau CLL, AML, Hodgkin's lymphoma (NHL), diffuse loj B-cell lymphoma (DLBCL) )) Thiab ntau tus mob myeloma (MM).