Ukusiza amangqamuzana abulalayo alalele izimpawu zokuzibulala
I-CLL yilona uhlobo oluvame kakhulu lwe- leukemia yabantu abadala . Njengezinye izinhlobo ze-leukemia, i-CLL yinkinga yegazi namaseli okwenza igazi. Ku-CLL, amaseli we-leukemia avame ukwakha kancane kancane ngokuhamba kwesikhathi. Abantu abakha i-CLL bangase babe nokuhlangenwe nakho okuhluke kakhulu, kepha ngokuvamile baxilongwa futhi baqhubeke bephila ngaphandle kwempawu nakancane, okungenani iminyaka embalwa.
Ngokuvamile kuba inani legazi elivamile elibonisa amazinga aphakeme lymphocyte amangqamuzana egazi amhlophe - futhi hhayi izimpawu ze-leukemia - eziluleka udokotela bese ekugcineni ziholela ekuxilongweni.
Izinhlobo
Izinhlobo ezahlukene ze-CLL ziziphatha ngokuhlukile. Abanye bakhula ngokushesha kunabanye. Amaseli e-leukemia avela ku-CLL akhula ngokushesha futhi akhula kancane ahlolisisa phezulu, kodwa ukuhlolwa kwelebhu kungasiza ukutshela umehluko phakathi kwabo. Ngokwesibonelo, amangqamuzana aqukethe amaprotheni aphansi okuthiwa i-ZAP-70 ne-CD38 acatshangwa ukuthi akhula kancane, ngokusho kwe-American Cancer Society.
Ezimweni ezithile ze-CLL, ingxenye ye-chromosome 17 ilahlekile-futhi kanye nayo, isakhi esibalulekile esilawula i-apoptosis (ukufa kwe-cell program) okuthiwa i-p53. Ukukhishwa kwe-17p kutholakala kumaphesenti angu-3 ukuya kwangu-10 abantu abangaphathwa kabi, kodwa amaphesenti angama-30 kuya kwangu-50 amacala aphinde avuliwe noma aphikisayo. Ngamanye amazwi, ukukhishwa kwe-17p kungase kube inkomba ye-CLL eyinkimbinkimbi yokuphatha.
Izibalo
Ngo-2016, kuzoba khona abantu ababalelwa ku-4,660 ezifweni e-United States. Nakuba izimpawu ze-CLL zingase zinyamalale isikhathi esithile ngemuva kokwelashwa kokuqala, lesi sifo kubhekwa singelapheki futhi abantu abaningi badinga ukwelashwa okwengeziwe, ngenxa yokubuya kwamangqamuzana anomdlavuza.
Ukuvunywa kwe-Venclexta FDA
I-Venclexta (i-venetoclax) iyona muthi yokuqala yohlobo lwayo okufanele ivunyiwe - yenzelwe ukusiza ukubuyisela ikhono leseli lokuzibhubhisa (i-apoptosis) ngokuvimbela ngokweqile amaprotheni we-BCL-2.
Njengoba kuphawuliwe ngenhla, i-CLL yisifo esingelapheki futhi sibuyele emuva, ngamaphesenti angama-30 kuya kwangu-50 abantu abakwa-CLL bathuthukile ekukhipheni kwe-17p, i-genetic marker ehambisana nesifo esinzima sokwelapha.
Lokhu kuvunywa kwe-FDA kusho ukuthi i-Venclexta iboniswa ukuphathwa kweziguli ezine-CLL ngokususwa kwe-17p, njengoba kutholakala uhlolo oluvunyelwe lwe-FDA, oluthole okungenani ukwelashwa kwangaphambi kokuqala. Ukuvunywa kwakusekelwe ekufuneni okuvela emtholampilo obizwa nge-M13-982 owabonisa izinga lama-80 jikelele lokuphendula nge-Venclexta.
Ukubaluleka kweziguli ezine-CLL
"Kuze kube yingxenye yabantu abaye baqhutshwa i-CLL ekuqhutshweni kwe-17p, isisindo somzimba esenza lesi sifo sibe nzima ukusiphatha," kusho uSandra Horning, MD, isikhulu sezokwelapha kanye nenhloko ye-Global Product Development. "I-Venclexta imithi yokuqala evunyelwe eklanyelwe ukuqala inqubo yemvelo esiza amangqamuzana ekubhubhiseni, futhi kuyindlela entsha yokusiza abantu abaye baphathwa ngaphambilini futhi babe nale ndlela ephakeme kakhulu yesifo."
I-Venclexta yanikezwa i-FDA Ukuqokwa Kwemithi Ye-Breakthrough ye-FDA yokwelashwa kwabantu abane-CLL ephulukisiwe (ephindaphindiwe noma ekhonjisiwe) ngokususwa kwe-17p. Ukwakhiwa kweTherapy Ukwelashwa kwenzelwe ukusheshisa ukuthuthukiswa kanye nokubuyekezwa kwemithi ehloselwe ukuphatha izifo ezinzima noma ezisongela ukuphila nokusiza ukuqinisekisa ukuthi abantu banokufinyelela kubo ngokugunyazwa kwe-FDA ngokushesha ngangokunokwenzeka. Isicelo Esisha Sezidakamizwa seVinclexta sanikezwa Ukubukezwa Okubalulekile, ukubizwa kwemithi i-FDA enqume ukuba nayo ingakwazi ukuhlinzeka ngokuthuthuka okukhulu ekunakekeleni, ekuvimbeleni noma ekuxilongweni kwesifo.
Iphrofayela yokuphepha
Imiphumela emibi engaba yingozi nge-Venclexta ifaka phakathi kwe-pneumonia, isibalo esincane segazi elimhlophe nge-fever, umkhuhlane, impendulo engavamile yamasosha omzimba okuholela ekubaleni kwegazi elibomvu eliphansi, isibalo esincane somzimba wegazi nesifo se-tumor lysis syndrome (TLS). Imiphumela emibi kakhulu ye-Venclexta ifaka inani elimhlophe legazi legazi, isifo sohudo, isisindo somswakama, isibalo esincane somzimba wegazi, ukutheleleka okuphezulu kokuphefumula, isibalo esiphansi seplatelet nokukhathala. Ukuhlaziywa kokuphepha okuhlanganisiwe kweziguli ezingu-240 ezine-CLL ephulukisiwe ngaphambili kusuka ezinkulweni ezintathu zokwelashwa kwabonisa imiphumela emibi kakhulu kwabikwa ngamaphesenti angu-43.8 weziguli. Imiphumela emibi ibanjwe ngokusekelwe ebubini, ngokuqina okukhulu okwenyuka kusuka ku-1 kuya ku-4. Imiphumela emibi kakhulu yeBanga 3 noma engu-4 yayilinganiselwe ukubalwa kwamangqamuzana egazi elimhlophe, inani elibomvu lesisindo segazi kanye nesibalo esincane seplatelet.
Ngokusho kukaPheobe Starr enkampanini kaFebruwari 2016 ethi "Impilo YaseMelika Nezidakamizwa," i-venetoclax inemisebenzi enamandla kakhulu yokuthi i-tumor lysis syndrome ibonakala iyinkinga enkulu kwizifundo zokuqala, kodwa lokhu kwaholela u-AbbVie (omunye wabaxhasi bezocwaningo) abaphenyi ukulungisa isimiso sokuguqula i-venetoclax, ukuqala ukwelashwa ngo-20 mg nsuku zonke futhi ukwandisa umthamo kancane kancane emavikini angu-4 ukuya emkhakheni we-400 mg nsuku zonke. Isilinganiso se-TLS nesimiso esisha sokulandelela sasingu-6 amaphesenti esilingo esibucayi, kungekho TLS emtholampilo.
Uhlelo lwe-FDA Lokuvunywa Ngokusheshisa luvumela ukuvunyelwa okunemibandela yomuthi ogcwalisa isidingo esingavumelekile sezokwelapha ngesimo esibucayi esekelwe ebufakazini bokuqala okusikisela ukuhlomula komtholampilo. Lesi sibonakaliso sivunyiwe ngaphansi kwemvume esheshayo ngokusezingeni lokuphendula jikelele. Ukuvunyelwa okuqhubekayo kwalesi sibonakaliso kungase kuhambisane nokuqinisekiswa kanye nencazelo yemhlomulo yomtholampilo ekuvivinyweni okuqinisekisiwe.
I-Venclexta ne-BCL-2
I-Venclexta iyi-molecule encane eyenzelwe ukukhetha nokuvimbela iphrotheni ye-BCL-2 ngokukhethayo, edlala indima ebalulekile enkambweni ebizwa ngokuthi i-apoptosis, noma ukufa kwe-cell ehleliwe - ngokuyinhloko i-apoptosis iyindlela yokulandelana komuntu siqu. I-Bcl-2 iyiprotheni elwa ne-apoptotic. Ngokuvimbela i-Bcl-2, i-Venetoclax, inomphumela we-pro-apoptotic emangqamuzaneni omdlavuza - iholela ekufweni kweseli okuhleliwe.
I-BCL-2 ithole igama layo kusukela ocwaningweni eyenziwe eminyakeni edlule ku- B-cell lymphomas . Ama-lymphocyte B noma ama-B-amangqamuzana, awuhlobo lwegazi elimhlophe. Ososayensi bafunde ukuthi izinguquko kuma-chromosomes kumaseli e-B zabangela ukuba igeneli le-Bcl-2 liqaliswe, okuvumela amangqamuzana ukuba asinde futhi akhule njengomdlavuza. Kusukela ngaleso sikhathi, ukubandakanyeka kwe-BCL-2 kuye kwafunyanwa kwezinye izinhlobo zamanqamu. Ngaphezu kwe-CLL, i-BCL-2 ibandakanyeka ku-melanoma, ibele, i-prostate kanye ne-lung cancer.
Njengoba kuphawuliwe, ngenhla, i-BCL-2 nayo iye yaxhunyaniswa namangqamuzana omdlavuza avimbela ukwelashwa. I-CLL yocingo-ikhiqiza amaprotheni e-BCL-2 iye yaxhunyaniswa nokumelana nemithi ethile. Kukholelwa ukuthi ukuvimbela i-BCL-2 kungabuyisa uhlelo lokubonisa ukuthi utshela amangqamuzana, kuhlanganise namaseli omdlavuza, ukuzibulala.
I-Venclexta ikhiqizwa ngu-AbbVie noGenentech, ilungu le-Roche Group. Ngokubambisana, izinkampani zizibophezele ukucwaninga noVenclexta, okwamanje okuhlolwayo ekuvivinyweni kokwelashwa kweSigaba III ukwelashwa kwe-CLL ephindaphindiwe, ephikisayo futhi engaphenduliwe, kanye nezifundo kwamanye amanyevuza.
Imithi yokwelapha ye-CLL
I-Venclexta ibuye ifundwe ngokuhambisana nezinye izidakamizwa ezisetshenziselwa ukulwa CLL. I-Venclexta imithi yokuqala evunyelwe eyenzelwe ukubuyisela i-apoptosis ngokuvimbela ngokukhetha ukuvikela iprotheyini ye-BCL-2 - futhi imithi entsha ye-Genentech entsha evunyiwe eminyakeni eyisikhombisa eyedlule.
Kuze kube manje, ezinye izidakamizwa ezintsha ezingu-3 zivunyiwe yi-FDA yokwelashwa kweziguli ezine-CLL, kuhlanganise ne- Bruton's kinase inhibitor ibrutinib (Imbruvica) , i-PI3K inhibitor idelalisib (iZydelig), ne-anti-CD20 obinutuzumab (Gazyva) .
Ngenxa yokuthi i-Venetoclax inendlela ehlukile, inamandla okuba usizo kakhulu ngokubambisana nezinye izidakamizwa ze-CLL ezinomsebenzi wokuhlanganisa.
Imithombo:
I-American Cancer Society. Liyini I-Chronic Lymphocytic Leukemia?
AbbVie Inc. Venclexta Ukuchazela Ulwazi.
Genentech, Inc. U-Genentech umemezela i-FDA Grants Venclexta ™ (Venetoclax) Ukuvunywa okusheshayo kwabantu abane-Hard-To-Treat Type of Chronic Lymphocytic Leukemia.
> Izinkombandlela Zokuziphatha Zomtholampilo ze-NCCN ku-Oncology. Inguqulo 1.2016.
> URoberts AW, Davids MS, uPagel JM, et al. Ukubhekela i-BCL2 ne-Venetoclax e-Relapsed Chronic Lymphocytic Leukemia. N Engl J Med . 2016; 374 (4): 311-22.
> Starr P. Venetoclax Ubonisa Umsebenzi Strong ku-CLL. Izinzuzo zeMpilo Nezidakamizwa zaseMelika. 2016; 9 (Spec Issue): 21.