Ukunceda iiseli ezibuhlungu ziphulaphule izibonakaliso ezonakalisayo
I-CLL luhlobo oluqhelekileyo lwe- leukemia yabantu abadala . Njengezinye iintlobo ze-leukemia, i-CLL yintlungu yegazi neeseli ezenza igazi. Kwi-CLL, iiseli ze-leukemia zakha ngokukhawuleza emva kwexesha. Abantu abaphuhlisa i-CLL banokuba namava ahluke kakhulu, kodwa kaninzi bafumaneka kwaye baqhubeka bephila ngaphandle kwempawu , ubuncinane kwiminyaka embalwa.
Ngokuqhelekileyo kubalo lwegazi eliqhelekileyo elibonisa amanqanaba aphezulu lymphocyte amaseli egazi amhlophe - kwaye ingekho iimpawu ze-leukemia - ukuba iingcebiso ugqirha kwaye ekugqibeleni zikhokelela ekuxilongweni.
Iintlobo
Iindidi ezahlukeneyo ze-CLL ziziphatha ngokwahlukileyo. Abanye bakhula ngokukhawuleza kunabanye. Iiseli ze-leukemia ezisuka ngokukhawuleza kwaye zikhula ngokuthe ngcembe iintlobo zeCLL zibukeka ngokufanayo phezulu, kodwa iimvavanyo zebhanki zinokukunceda ukuxelela umahluko phakathi kwabo. Ngokomzekelo, iiseli eziqulethe ixabiso elincinane leeprotheni ezibizwa ngokuba yi-ZAP-70 kunye neCD38 zicingelwa ukuba zikhule ngokuthe ngcembe, ngokutsho kwe-American Cancer Society.
Kwiimeko ezithile ze-CLL, inxalenye ye-chromosome 17 ilahlekile-kwaye kunye nayo, i-gene ebalulekileyo elawula i-apoptosis (ukufa kweseli ehleliweyo) ebizwa nge-p53. Ukususwa kwe-17p kufumaneka kwi-3 ukuya kwi-10 ekhulwini yabantu abangaphatanga ngaphambili, kodwa ukufikelela kuma-30 ukuya kuma-50 ekhulwini amaxesha aphinde ahlaselwa okanye aphikisayo. Ngamanye amazwi, ukususwa kwe-17p kungabonakalisa inkqubo yokusebenza ngokugqithiseleyo i-CLL.
Izibalo
Ngo-2016, kuya kuqikelelwa ukufa kwabangu-4,660 kwisifo e-United States. Nangona iimpawu ze-CLL zingahle zinyamalale ixesha elithile emva kokuqala unyango, lesi sifo sithathwa singenakuphulukiswa kwaye abantu abaninzi baya kufuna unyango olongezelelweyo, ngenxa yokubuya kweeseli zomhlaza.
Venclexta FDA imvume
I-Venclexta (venetoclax) yonyango lokuqala lohlobo lwayo ukuba lugunyazwe - lenzelwe ukubuyisela amandla eseli ekuzibhubhiseni (apoptosis) ngokunqanda ngokunyanisekileyo iphrotheni ye-BCL-2.
Njengoko kuphawuliwe ngasentla, i-CLL isifo esingenakuphulukana kunye nokuphindaphinda kuqhelekileyo, kunye nabantu abangama-30 ukuya kuma-50 ekhulwini abantu abaqhubekileyo be-CLL baqhuba ukususwa kwe-17p, i-marker marker ehambelana nezifo ezinzima ukunyanga.
Ukwamkelwa kwe-FDA kuthetha ukuba uVetclexta uboniswe ukuba unyango lwezigulane nge-CLL kunye nokucima kwe-17p, njengoko kufunyenwe uvavanyo oluvunyiweyo lwe-FDA, oluye lwafumana ubuncinane lonyango lokuqala. Ukuvunywa kwakusekelwe kwiziphumo ezivela kwizifundo zeklinikhi ezibizwa ngokuba yi-M13-982 ezibonisa i-80 ekhulwini izinga lokuphendula nge-Venclexta.
Ukubaluleka kwezigulane nge CLL
"Kuze kube kwisiqingatha sabantu abaqhubekileyo beCLL baqhubekile ukukhishwa kwe-17p, umenzi wempawu eziphathekayo obangela ukuba le nto ilukhuni ukuyiphatha," kutsho uSandra Horning, MD, igosa lonyango eliphambili kunye nentloko ye-Global Product Development. "I-Venclexta yonyango lokuqala elivunyiweyo elenzelwe ukuqala inkqubo yendalo eyenza iiseli zizitshabalalise, kwaye yindlela entsha yokunceda abantu abaye baphathwa ngaphambili kwaye banalo hlobo olubi kakhulu lwesifo."
U-Venclexta wanikezwa iCommissioning Treatment Designation yi-FDA yokonyango lwabantu abaye baphathwa ngokugqithiseleyo (ukuphindaphinda okanye ukukhanyela) CLL kunye nokususwa kwe-17p. Ukuqulunqwa kweNyango yeCandelo loPhuhliso lenzelwe ukukhawulezisa uphuhliso kunye nokuhlaziywa kwamachiza okujoliswe ekuphatheni izifo ezinzulu okanye ezisongela ubomi kunye nokuncedisa ukuqinisekisa ukuba abantu banokufikelela kubo kwi-FDA imvume ngokukhawuleza. Isicelo Esitsha seMithi ye-Venclexta sanikezwa ukuHlola okuPhambili, ukutyunjwa kwamachiza ama-FDA anqwenele ukuba anakho ukubonelela ngempumelelo kunyango, ukukhusela okanye ukuxilongwa kwesifo.
IProventic Safety
Imiphumo emibi kakhulu enokuthi i-Venclexta ifake i-pneumonia, i-white white cell cell count with fever, imfiva, impendulo engavamile yomzimba eyenza ibalo elibomvu le-cell count , i-red red count count kunye ne-tumor lysis syndrome (TLS). Iziphumo eziqhelekileyo ezichaphazelekayo zeVenclexta ziquka inani elincinci legazi legazi, isifo sohudo, isisu, isisombululo segazi esilula, isifo sokuphefumula esiphezulu, isibalo esiphantsi seplatelet kunye nokukhathala. Uhlalutyo olukhuselekileyo lwezokhuseleko lwezigulane ezingama-240 ezine-CLL eziphethwe ngaphambili zivela kwizilingo ezintathu zonyango lubonise imiphumo emibi echazwe kuma-43.8 ekhulwini kwizigulane. Imiphumo emibi ifakwe kwisiseko esiqinileyo, ngokunyuka kwenyuka ukusuka kwi-1 kuya kwe-4. Iimpembelelo eziqhelekileyo zeBakala 3 okanye ezine zazininzi ze-white white count count, count count cell count and count countlet count.
Ngokutsho kwePhephe Starr kwimiba ka-Febhuwari 2016 ye-"Impilo yeMerika kunye neZonyango zeMithi," venetoclax inomsebenzi onamandla kakhulu wokuba i-tumor lysis syndrome ibonakale njengenkxalabo enkulu kwizifundo zokuqala, nangona oko kukhokelela u-AbbVie (omnye wabaxhasi bezifundo) kunye abaphandi ukuba bahlengahlengele i-dosing schedule ye-venetoclax, ukuqala unyango kwi-20 mg yemihla ngemihla kwaye ukwandisa umthamo ngokukhawuleza ngaphezu kweeveki ezi-4 ukuya kwiqondo elijoliswe ku-400 mg ngosuku. Isilinganiselo se-TLS ngeshedyuli entsha ye-dosing yayingama-6 ekhulwini kwilingo eliphambili, kungekho TLS yeklinikhi.
Inkqubo yokuVunywa kwesiKhwama se-FDA ivumela imvume echanekileyo yonyango egcwalisa imfuno yonyango engagqibekanga imeko esekelwe kubungqina bokuqala obubonisa ukuba inzuzo yeklinikhi. Esi sibonakaliso sivunyiwe phantsi kokuvunyelwa ngokukhawuleza ngokusekelwe kumyinge wokuphendula jikelele. Ukuvunyelwa okuqhubekayo kwesi sibonakaliso sinokungqinelana nokuqinisekiswa kunye nenkcazo yenzuzo yekliniki kwiimvavanyo eziqinisekisiweyo.
Venclexta kunye ne-BCL-2
I-Venclexta i-molecule encinci eyenzelwe ukubopha kunye nokuvimbela iprotheni ye-BCL-2, edlala indima ebalulekileyo kwinkqubo ebizwa ngokuba yi-apoptosis, okanye ukufa kweselungisiwe-ngokukodwa i-apoptosis yindlela elandelelanayo yokutshatyalaliswa kwamaselula. I-Bcl-2 yiprotheni yokulwa ne-apoptotic. Ngokuvimbela i-Bcl-2, i-Venetoclax, ine-pro-apoptotic inomhlaza kwintsholongwane - ityhila ukufa kweseli.
I-BCL-2 inegama layo kwiphando eyenziwe kwiminyaka edlulileyo kwi- B-cell lymphomas . I-B-lymphocytes, okanye iiseli ze-B, zihlobo lwegazi elimhlophe. Oososayensi bafunde ukuba utshintsho kuma-chromosomes kwiiseli ze-B lubangela ukuba i-gene ye-Bcl-2 iqaliswe, ivumela iiseli ukuba ziphile kwaye zikhule njengomhlaza. Ukususela ngelo xesha, ukubandakanywa kwe-BCL-2 kuye kwafunyanwa kwezinye iindawo zamanye amagciwane. Ukongeza kwi-CLL, i-BCL-2 ibandakanyeka kwi-melanoma, ibele, i-prostate kunye ne-lung cancer.
Njengoko kuphawuliwe, ngasentla, i-BCL-2 nayo idibene nomhlaza wesifo somhlaza. I-CLL yokuba ubuninzi-ivelise iprotheni ye-BCL-2 idibene nokuxhatshazwa kwamachiza athile. Kukholelwa ukuba ukukhusela i-BCL-2 kunokubuyisela inkqubo yokubonakalisa etshela iiseli, kuquka namaseli esifo somhlaza, ukuba zibhubhise.
I-Venclexta iphuhliswa ngu-AbbVie noGenentech, ilungu leQela laseRoche. Ngokubambisana, iinkampani zizimisele ukuphanda nge-Venclexta, okwangoku iphononongwa kwiiNqanaba III zezilingo zonyango ukwenzela unyango lwe-CLL, kwakhona kunye nezifundo kwezinye iindiza ezinomdlavuza.
Iipilisi ezikhulayo ze-CLL
I-Venclexta iphinda ifundwe kunye nezinye iziyobisi ezisetyenziswa ukulwa neCLL. I-Venclexta yiyeza lokuqala elivunyiweyo elenzelwe ukubuyisela i-apoptosis ngokunqanda ngokunyanisekileyo iphrotheni ye-BCL-2 kunye neyeza likaGenentech elitsha le-10 elivunyiwe kwiminyaka esixhenxe eyadlulayo.
Kule ndlela, ezinye izidakamizwa ezitsha zivunyiwe ngu-FDA ukwenzela unyango lwezigulane nge-CLL, kubandakanywa ne- Bruton's kinase inhibitor ibrutinib (i-Imbruvica) , i-PI3K inhibitor idelalisib (iZydelig), kunye ne-anti-CD20 obinutuzumab (Gazyva) .
Ngenxa yokuba uVenetoclax unendlela eyahlukileyo, inokukwazi ukuba luncedo ngokubambisana nezinye izidakamizwa ze-CLL ezineendlela zokwenza izinto ezincedisayo.
Imithombo:
American Cancer Society. Yintoni I-Lymphocytic Leukemia?
AbbVie Inc. Venclexta Ukuchazela ulwazi.
UGenentech, Inc. U-Genentech Uvakalisa i-FDA Izibonelelo ze-Venclexta ™ (Venetoclax) Ukuvunyelwa okukhawulezileyo kubantu abane-Hard-To-Treat Type of Chronic Lymphocytic Leukemia.
> I-NCCN Izikhokelo zoLwazi lweZikliniki kwi-Oncology. Version 1.2016.
> Roberts AW, Davids MS, Pagel JM, et al. Ukujolisa i-BCL2 kunye neVenetoclax kwiLukemia yeLymphocytic Chronicle. N Engl J Med . 2016; 374 (4): 311-22.
> Starr P. Venetoclax Ubonisa umsebenzi onamandla kwi-CLL. IiMpilo zeMelika kunye neNkunkuma yamayeza. 2016; 9 (Inkcazo ethile): 21.