Kuthandiza maselo owonongeka amamvetsera zizindikiro zokhazokha
CLL ndi mtundu wofala kwambiri wa khansa ya m'magazi akuluakulu . Monga mitundu ina ya khansa ya m'magazi, CLL ndi kuwonongeka kwa magazi ndi maselo opanga magazi. Mu CLL, maselo a khansa ya m'magazi amapanga pang'onopang'ono pakapita nthawi. Anthu amene amalimbikitsa CLL akhoza kukhala ndi zosiyana kwambiri, koma nthawi zambiri amapezeka ndikupitirizabe kukhala opanda zizindikiro , kwa zaka zochepa chabe.
Kawirikawiri ndi chizoloŵezi chowerengera magazi chomwe chimasonyeza maulendo akuluakulu a lymphocyte maselo oyera a magazi - osati zizindikiro za khansa ya m'magazi - malangizowo a dotolo ndipo potsirizira pake amatsogolera kuchipatala.
Mitundu
Mitundu yosiyanasiyana ya CLL imachita mosiyana. Ena amakula mwamsanga kuposa ena. Maselo a khansa ya m'magazi ochokera ku mtundu wa CLL okula mofulumira komanso ochepa pang'onopang'ono amawonekera pamwamba, koma mayesero a ma labulo angathandize kusiyanitsa pakati pawo. Mwachitsanzo, maselo omwe ali ndi mapuloteni otsika otchedwa ZAP-70 ndi CD38 akuganiza kuti amakula pang'onopang'ono, malinga ndi American Cancer Society.
Nthaŵi zina za CLL, gawo la chromosome 17 latayika - ndipo limodzi ndilo, jini lofunika kwambiri lomwe limayang'anira mapulogalamu apadera (programmed cell death) wotchedwa p53. Kuchotsedwa kwa 17p kumapezeka 3 mpaka 10 peresenti ya anthu osaphunzitsidwa kale, koma mpaka 30 mpaka 50 peresenti ya milandu yobwereranso kapena yotsutsa. Mwa kuyankhula kwina, kuchotsa 17p kungakhale chizindikiro cha zovuta kwambiri zochitira CLL.
Ziwerengero
Mu 2016, anthu pafupifupi 4,660 adzafa kuchokera ku matendawa ku United States. Ngakhale kuti zizindikiro za CLL zingawonongeke kwa kanthaŵi kochepa chithandizo chitachitika, matendawa amachiritsidwa osachiritsika ndipo anthu ambiri amafunikira thandizo linalake, chifukwa cha kubwerera kwa maselo a khansa.
Venclexta FDA Chivomerezo
Venclexta (venetoclax) ndi mankhwala oyamba a mtunduwu kuti avomerezedwe - yapangidwa kuti athandize kubwezeretsa mphamvu ya selo kuti iwonongeke (apoptosis) potseka puloteni ya BCL-2.
Monga tafotokozera pamwambapa, CLL ndi matenda osachiritsika ndipo amabwereranso, ndipo anthu 30 mpaka 50 peresenti ya anthu omwe CLL yawo idapitilira kuchotsa 17p, chizindikiro chokhala ndi matenda ovuta kuchiza.
Chivomerezochi cha FDA chikutanthauza kuti Venclexta imasonyezedwa pochiza odwala omwe ali ndi CLL ndi 17p kuchotsa, monga atayesedwa ndi mayeso ovomerezeka a FDA, omwe adalandira mankhwala osachepera amodzi. Chivomerezocho chinachokera pa zomwe anapeza kuchokera ku kafukufuku wamakono wotchedwa M13-982 omwe amasonyeza 80 peresenti ya chiwerengero cha mayankho ndi Venclexta.
Kufunika kwa Odwala Ndi CLL
"Kufikira theka la anthu omwe CLL yawo ikupita kuti isachotsere 17p, chiwerengero chomwe chimachititsa kuti matendawa azivutika," adatero Sandra Horning, MD, wamkulu wa zachipatala komanso a Global Product Development. "Venclexta ndi mankhwala ovomerezeka oyambirira omwe amachititsa kuti pakhale njira zachilengedwe zomwe zimathandiza maselo kudziwononga, ndipo ndi njira yatsopano yothandizira anthu amene anachiritsidwa kale ndipo ali ndi matendawa."
Venclexta anapatsidwa Chipatala Chokhazikitsa Chithandizo cha FDA kuti athe kuchiritsira anthu omwe ali ndi CLL omwe amachiritsidwa kale (ochotsedwa kapena otsutsa) ndi kuchotsa 17p. Njira Yothandizira Kukonzekera Kukonzekera kwapangidwa kuti zifulumizitse chitukuko ndi kuyambiranso kwa mankhwala omwe akufuna kulandira matenda oopsa kapena owopsya komanso kuwathandiza kuti anthu athe kuwayendera kudzera ku chivomerezo cha FDA mwamsanga. Kugwiritsa ntchito mankhwala atsopano kwa Venclexta kunapatsidwa Kukambitsirana Kwambiri, kutchulidwa kwa mankhwala omwe FDA yatsimikiza kuti ikhoza kuthetsa kusintha kwakukulu, kuchiza kapena matenda a matenda.
Pulogalamu yachitetezo
Zotsatira zoopsa zowopsa ndi Venclexta ndi chibayo, selo loyera la magazi loyera limakhala ndi malungo, kutentha thupi, kutentha kwa thupi kumatenda komwe kumabweretsa chiwerengero chochepa cha maselo ofiira a magazi , chiwerengero chochepa cha maselo ofiira a m'magazi ndi tumor lysis syndrome (TLS). Zotsatira zowopsa za Venclexta ndi kuchuluka kwa maselo oyera a magazi, kutsegula m'mimba, kunyowa, kuchepa kwa maselo ofiira a m'magazi, kuthamanga kwapakati pamutu, kuwerengeka kwapopereti ndi kutopa. Kusanthula kwa chitetezo cha odwala 240 omwe anali ndi CLL ochiritsidwa kale kuchokera m'mayesero atatu a chipatala anawonetsa zotsatira zoyipa zomwe zinafotokozedwa mu 43.8 peresenti ya odwala. Zotsatira zake zimagwiritsidwa ntchito mopitirira muyeso, ndi kuwonjezeka kowonjezereka mukupita kuchoka pa 1 mpaka 4. Zotsatira zoyamba za Gawo 3 kapena 4 ndizochepa zoyera maselo a magazi, chiwerengero chochepa cha maselo ofiira a m'magazi ndi chiwerengero chochepa cha platelet.
Malingana ndi Pheobe Starr mu magazini ya February 2016 ya "American Health and Drug Benefits," venetoclax ali ndi mphamvu zoterezi zomwe zimachititsa kuti vuto lopweteka lysis likhale lovuta kwambiri pa maphunziro oyambirira, komabe izi zinatsogolera AbbVie (mmodzi mwa othandizira maphunziro) ndi Ofufuza amawongolera ndondomeko yoyenera ya matenda a venetoclax, kuyambitsa chithandizo pa 20 mg tsiku ndi tsiku ndikuwonjezereka mlingo pang'onopang'ono kwa masabata anayi kufika pa mlingo wa 400 mg tsiku lililonse. Chiwerengero cha TLS ndi ndondomeko yatsopanoyi inali 6 peresenti mu kuyesayesa kwakukulu, popanda TLS zachipatala.
Chipatala cha FDA chachangu chovomerezeka chimalola kuvomerezedwa kwa mankhwala omwe amadzaza chilakolako chosafunikira cha kuchipatala chifukwa cha zovuta zoyambirira zomwe zimapereka chithandizo choyenera. Chizindikiro ichi chimavomerezedwa pansi pa kuvomerezedwa kwachangu chifukwa cha chiwerengero cha mayankho onse. Kupitiliza kuvomereza kuti chiwonetserochi chikhoza kukhala chotsimikizirika ndi kufotokoza kwa phindu lachipatala mu mayesero ovomerezeka.
Venclexta ndi BCL-2
Venclexta ndi kamolekyu kakang'ono kamene kamasankhidwa kuti asamangidwe ndi kulepheretsa mapuloteni a BCL-2, omwe amathandiza kwambiri pulogalamu yotchedwa apoptosis, kapena programmed cell death - makamaka apoptosis ndi maselo omwe amadziwonongera okha. Bcl-2 ndi mapuloteni odana ndi apoptotic. Poletsa Bcl-2, Venetoclax, imakhala ndi zotsatira zenizeni pa maselo a khansa - imapangitsa kuti maselo apangidwe afe.
BCL-2 imachokera kufukufuku omwe adachitika zaka zapitazo pa B-cell lymphomas . B-lymphocytes, kapena B-maselo, ndi mtundu wa magazi oyera. Asayansi anaphunzira kuti kusintha kwa ma chromosome m'maselo a B kunachititsa kuti Bcl-2 isinthidwe, kuti maselo apulumuke ndi kukula monga khansara. Kuchokera nthawi imeneyo, kutenga nawo mbali kwa BCL-2 kunapezedwanso m'magazi ena ambiri a kansa. Kuwonjezera pa CLL, BCL-2 imakhudzidwa ndi khansa ya khansa, mawere, prostate ndi khansa ya m'mapapo.
Monga taonera, pamwambapa, BCL-2 yakhalanso ndi maselo a kansa omwe amatsutsa. CLL yochuluka-imapanga mapuloteni a BCL-2 yakhala ikugwirizana ndi kukana mankhwala ena. Zimakhulupirira kuti kuletsa BCL-2 kungabwezeretse dongosolo lozindikiritsa lomwe limauza maselo, kuphatikizapo maselo a khansa, kuti awonongeke.
Venclexta ikupangidwa ndi AbbVie ndi Genentech, membala wa Roche Group. Pamodzi, makampaniwa akudzipatulira kufufuza ndi Venclexta, omwe akuyang'aniratu panjira zochizira matenda a Phase III kuti athe kuchiritsidwa, kubwezeretsa komanso kusamalidwa CLL, kuphatikizapo maphunziro ena ambiri khansa.
Mankhwala Othandiza a CLL
Venclexta ikuphunziranso kuphatikizapo mankhwala ena omenyana ndi CLL. Venclexta ndi mankhwala ovomerezeka oyambirira kuti athetseretu mapuloteni mwa kutseka chitetezo cha BCL-2 - ndipo ndi mankhwala atsopano a Genentech omwe amavomerezedwa zaka zisanu ndi ziwiri zapitazo.
Pakalipano, mankhwala ena atsopano atatu adavomerezedwa ndi FDA kuti azitsatira odwala omwe ali ndi CLL, kuphatikizapo Bruton's kinase inhibitor ibrutinib (Imbruvica) , PI3K inhibitor idelalisib (Zydelig), ndi obinutuzumab anti-CD20 (gazyva) .
Chifukwa Venetoclax ili ndi njira yosiyana, imakhala yothandiza kwambiri kuphatikizapo mankhwala ena a CLL omwe ali ndi njira yowonjezeramo.
Zotsatira:
American Cancer Society. Kodi N'chiyani Chimachititsa Lymphocytic Leukemia?
AbbVie Inc. Venclexta Kulongosola Zowonjezera.
Genentech, Inc. Genentech Adalengeza FDA Grants Venclexta ™ (Venetoclax) Kuvomerezedwa Kwachangu kwa Anthu Amene Ali ndi Matenda Ovuta Kwambiri a Lymphocytic Leukemia.
> Zotsatira za NCCN zowunikira zowonjezereka m'magulu oncology. Version 1.2016.
> Roberts AW, Davids MS, Pagel JM, et al. Kuwongolera BCL2 ndi Venetoclax mu Relapsed Chronic Lymphocytic Leukemia. N Engl J Med . 2016; 374 (4): 311-22.
> Starr P. Venetoclax Akuwonetsa Ntchito Yamphamvu mu CLL. Mapindu a American Health & Drug. 2016; 9 (Nkhani Yeniyeni): 21.