Kubatsira masero anotyisa anoteerera zviratidzo zvinoparadza
CLL ndiyo iyo inowanzove yakakura yeukweukemia . Kufanana nemamwe marudzi eukemia, CLL inonyangadza ropa neropa-forming masero. MuCLL, masero eukemia anovaka zvishoma nezvishoma. Vanhu vanokura CLL vanogona kunge vane zviitiko zvakasiyana zvakasiyana, asi kazhinji vanoongororwa uye vanoenderera mberi vachirarama vasina zviratidzo zvachose, kwemakore mashomanana.
Kazhinji inoratidzirwa ropa inoratidza kuwanda kwemajeri emasero eropa-uye kwete zviratidzo zveukemukari - izvo zvinokurapa chiremba uye uye pakupedzisira zvinotungamirira kuongororwa.
Aina
Mhando dzakasiyana dzeCLL dzinoita zvakasiyana. Vamwe vanokura nokukurumidza kupfuura vamwe. Masero eukemia kubva kukurumidza-kukura uye kukura zvishoma nezvishoma CLL maitiro anotarisa zvakafanana pamusoro pepamusoro, asi maitiro ekuraira anogona kubatsira kutaurira musiyano pakati pavo. Semuenzaniso, masero ane zvishoma zveprotein anonzi ZAP-70 neCD38 anofungidzirwa kuti anokura zvishoma nezvishoma, maererano neAmerican Cancer Society.
Mune zvimwe zviitiko zveCLL, chikamu chechiromosome 17 chinorasika-uye pamwe chete nacho, geni rinokosha rinodzora apoptosis (programmed cell cell death) inonzi p53. Kubvisa 17p kunowanikwa mu3 kusvika ku10 muzana yevanhu vasati vasiri kutorwa, asi kusvika 30 kusvika ku50 muzana yezvezvekare kana kuti dzisina kukodzera. Mune mamwe mazwi, kubvisa 17p kunogona kuva chiratidzo chekuoma-kubata-CLL.
Statistics
Muna 2016, pachave nekufungidzirwa kufa kwevanhu vana mazana mana nemakumi mana kubva muhutano muUnited States. Kunyange zvazvo zviratidzo zveCLL zvingangopera kwenguva yakati mushure mekutanga kurapwa, chirwere chacho chinonzi chisingaregi uye vanhu vazhinji vachada kurapwazve, nekuda kwekudzoka kwemasero ane kenza.
Venclexta FDA Chibvumirano
Venclexta (venetoclax) ndiyo yekutanga mushonga werudzi rwayo kugamuchirwa - yakagadzirirwa kubatsira kubatsira sero kukwanisa kuparadza (apoptosis) nekudzivisa zvakasimba mapuroteni eBCL-2.
Sezvambotaurwa pamusoro apa, CLL chirwere chisingaregi uye kudzokerazve kunowanzoonekwa, uye kusvika 30 kusvika ku50 kubva muzana yevanhu avo CLL yakafambira mberi yekuporesa 17p, genetic marker inobatanidza nekuoma-kubata-kurapa chirwere.
Iyi mvumo yeDAA inoreva kuti Venclexta inoratidzirwa mukurapa kwevarwere vane CLL ne 17p deletion, sezvakaonekwa neDAA inobvumidzwa kuedzwa, avo vakagamuchira kamwe musati wapera. Chibvumirano chacho chakavakirwa pane zvakawanikwa kubva kuchipatara chinonzi M13-982 iyo yakaratidza 80 muzana yehuwandu hwemhinduro yekuita ne Venclexta.
Kukosha Kwevarwere NeCLL
"Kusvikira hafu yevanhu avo CLL yakafambira ine 17p kubvisa, genetic marker iyo inoita kuti chirwere chacho chiomerwe-kurapa," akadaro Sandra Horning, MD, chiremba mukuru uye mukuru we Global Global Development. "Venclexta ndiyo mishonga inotenderwa kutanga yakagadzirirwa kugadzirisa nzira yemhuka inobatsira masero kuzvidya, uye inzira itsva yekubatsira vanhu vakamborapwa uye vane utano hwepamusoro hwechirwere ichi."
Venclexta yakapiwa Breakthrough Therapy Dhiyabhorosi neDDA yekurapa kwevanhu vakambotapwa (vakadzoka zvakare kana kuti vasingadi) CLL ne 17p deletion. Kuparadzanisa Utachiona Kurongwa kwakagadzirirwa kukurumidza kufambisa uye kuongororwa kwemishonga inotarisirwa kutarisa zvirwere zvakakomba kana zvinopisa upenyu uye kubatsira kubatsira vanhu kuti vashandise kuburikidza neDAA kubvumirwa nokukurumidza. Izwi reDrug Drug Application for Venclexta rakapiwa Kubvunzurudzwa Kwekutanga, chirongwa chemishonga iyo FDA yakasarudza kuva nekwanisi yekugadzirisa zvikuru mukurapa, kudzivirira kana kuongororwa kwechirwere.
Safety Profile
Zvimwe zvinokonzerwa nemigumisiro yakakomba neVetclexta inosanganisira pneumonia, masero machena eropa anoverengerwa nefivha, fivha, kusagadzikana kwemasimba emuviri kunokonzera pasi shoma rekuyera ropa, count red blood cell count uye tumor lysis syndrome (TLS). Zvimwe zvinowanzovhiringidza zveVetclexta zvinosanganisira kuchena kwemasero eropa ropa, chirwere, chirwere chinopisa, kusuruvara kwemasero emasero eropa, kuputika kwepamusoro maitiro ekutapukisa, low platelet count uye kuneta. Chirongwa chekuchengetedzwa kwekuchengetedzwa kwevane 240 vane chirwere chekare chakatarisirwa kubva kumakirini matatu emakiriniki vakaratidza kukanganisa kwakakonzerwa muna 43.8 muzana yevarwere. Zvimwe zvinokonzerwa zvakasimbiswa zvichienderana nekuoma, nekuwedzera kwakanyanya iwe unobva kubva kuna 1 kusvika ku4. Yakanyanya kuwanda yeGeorge 3 kana 4 migumisiro yechirwere yaiva yakachena yeropa rekuyera nhamba, yakadzivirirwa yeropa rekuyera masero uye low platelet count.
Maererano nePeople Starr mumagazini yaFebruary 2016 e "American Health and Drug Benefits," venetoclax ine basa rakasimba rakasimba rekuti tumor lysis syndrome yakabuda sechinhu chinonyanya kukosha muzvidzidzo zvepakutanga, zvisinei izvi zvakaita kuti AbbVie (mumwe wevatsigiri vekudzidza) uye vatsvakurudzi kugadzirisa dosing purogiramu ye venetoclax, kutanga chirwere pa 20 mg zuva rega rega uye kuwedzerwa chirwere zvishoma nezvishoma kupfuura masvondo mana kusvika pane chinangwa che 400 mg zuva nezuva. Mutengo weTLS newaini dosing purogiramu yaiva 6 muzana mumutambo unokosha, usina kliniki TLS.
Dhiyabhorosi yeDefed's Approved Approval Program inobvumidza mvumo yepamutemo yemishonga inozadza chirwere chisina kufanira chechipatara chechimiro chakakomba chinoenderana nehupupuriro hwepakutanga hunoratidza kuti chirwere chinobatsira. Ichi chiratidzo chinogamuchirwa pasi pekugamuchirwa kwepamusoro zvichienderana nehuwandu hwemhinduro yekuita. Kuenderera mberi kugamuchirwa kwechiratidziro ichi kunogona kunge kuchienderana nekunzvera uye tsanangudzo yemakiriniki anobatsira muzvidzidzo zvinosimbisa.
Venclexta uye BCL-2
Venclexta ikamu korojekiti yakagadzirirwa kusarudza uye inodzivisa protein yeBBCL-2, iyo inobata basa rinokosha mukugadzirisa kunonzi apoptosis, kana programmed cell death - kunyanya apoptosis inofanana nemagadzirirwo ehupenyu hwekuparadza. Bcl-2 iproteti inorwisa-apoptotic. Nokudzivisa Bcl-2, Venetoclax, ine pro-apoptotic inoitwa nekenza masero - inokonzera programmed cell sefa.
BCL-2 yakawana zita rayo kubva pakutsvakurudza kwakaitwa makore akapfuura paB-cell lymphomas . B-lymphocytes, kana B-masero, ndiwo rudzi rwehuchenzi ropa. Masayendisiti akadzidza kuti kuchinja kune ma kromosomes mumasero eB kwakaita kuti Bcl-2 gene ishandiswe, zvichibvumira masero kuti ararame uye akure sekenza. Kubvira panguva iyo, kubatanidzwa kweBBCL-2 kwave kuwanikwawo mune dzimwe nhamba dzekenza. Mukuwedzera kune CLL, BCL-2 inobatanidzwa mu melanoma, mazamu, prostate uye maperembudzi emapapu.
Sezvakataurwa, pamusoro, BCL-2 yave ichibatanidzwa nemasero emukenza anoramba kurapwa. CLL iyo yakawanda-inobudisa BCL-2 protein yakabatanidzwa mukurwisa mamwe mishonga. Inofungidzirwa kuti kudzivirira BCL-2 kunogona kudzorera zviratidzo zvinotaurira masero, kusanganisira masero emukenza, kuzviparadza.
Venclexta irikudziridzwa naAbbVie naGenentech, nhengo yeRoche Group. Pamwe chete, makambani akazvipira kutsvakurudza naVenclexta, ikozvino iri kuongororwa muPatse III matanho emakiriniki ekurapa kwekudzorerwazve, kukanganisa uye zvisati zvamboitwa CLL, pamwe nekuongorora mune dzimwe mimwe makondombera.
Emerging Therapies for CLL
Venclexta irikudzidziswawo pamwe chete nedzimwe mishonga inoshandiswa kurwisana CLL. Venclexta ndiyo mishonga inotenderwa yakagadzirirwa kugadzirisa apoptosis nokuvhara mapuroteni eC -LL-2-uye ndiyo mishonga yeGenentech yegumi yakagamuchirwa mumakore manomwe apfuura.
Kusvika ikozvino, mamwe mishonga mitatu mitsva yakagamuchirwa neRDA yekurapa varwere vane CLL, kusanganisira Bruton's kinase inhibitor ibrutinib (Imbruvica) , PI3K inhibitor idelalisib (Zydelig), uye anti-CD20 obinutuzumab (Gazyva) .
Nokuti Venetoclax ine nzira yakasiyana, iyo inogona kuva yakakosha mukubatana nedzimwe mishonga yeLLL iyo inobatanidza nzira yekuita.
Sources:
American Cancer Society. Chii Chinonzi Chronic Lymphocytic Leukemia?
AbbVie Inc. Venclexta Kududzira Mashoko.
Genentech, Inc. Genentech Anozivisa FDA Grants Venclexta ™ (Venetoclax) Kubvumidza Kubvumirwa Kwevanhu vane Dambudziko Rokubata Mhando yeHist Lymphocytic Leukemia.
> NCCN Clinical Practice Guidelines muna Oncology. Version 1.2016.
> Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 ne Venetoclax muReapsed Chronic Lymphocytic Leukemia. N Engl J Med . 2016; 374 (4): 311-22.
> Starr P. Venetoclax Inoratidza Basa Rakasimba muCLL. American Health & Drug Benefits. 2016; 9 (Spec Issue): 21.