Mankhwala Osokoneza Bongo Acalabrutinib: Chithandizo cha CLL / SLL / MCL - AASraw
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Mankhwala Osokoneza Bongo Acalabrutinib

 

  1. Acalabrutinib Kubwerera kumbuyo
  2. Ndemanga za Acalabrutinib
  3. Chithandizo cha Acalabrutinib (Chogwiritsira ntchito)
  4. Njira ya Acalabrutinib Ya Ntchito
  5. Kodi zotsatira zoyipa za Acalabrutinib ndi ziti?
  6. Acalabrutinib VS Ibrutinib
  7. Kafukufuku: Acalabrutinib Pochiza Matenda a m'magazi (CLL)

 

Acalabrutinib Kubwerera kumbuyo

Mpaka pano, acalabrutinib yakhala ikugwiritsidwa ntchito poyesa kuphunzira zamankhwala a B-All, Myelofibrosis, Ovarian Cancer, Multiple Myeloma, ndi Hodgkin Lymphoma, pakati pa ena.

Kuyambira pa Okutobala 31, 2017 a FDA adavomereza Astra Zeneca yomwe idaperekedwa pakamwa Calquence (acalabrutinib). Bruton Tyrosine Kinase (BTK) inhibitor akuwonetsa kuti azichiza matenda a khansa ya m'mimba, lymphocytic lymphoma, komanso odwala achikulire omwe ali ndi Mantle Cell Lymphoma (MCL) omwe alandirapo kale kamodzi.

Amadziwikanso monga Zamgululi, acalabrutinib imawonedwanso ngati m'badwo wachiwiri wa BTK inhibitor chifukwa idapangidwa mwanzeru kuti ikhale yamphamvu kwambiri komanso yosankha kuposa ibrutinib, mwachidziwikire kuti ikuyembekezeka kuwonetsa zovuta zochepa chifukwa chochepetsa zomwe zikuyimira pazowonjezera zina kupatula BTK.

Komabe, acalabrutinib idavomerezedwa munjira yovomerezeka mwachangu ya FDA, yomwe imakhazikitsidwa potengera kuyankha konse ndikuthandizira kuvomerezedwa koyambirira kwamankhwala omwe ali ndi vuto lalikulu kapena / komanso omwe amakwaniritsa zosowa zamankhwala zosakwaniritsidwa kutengera kumapeto kwa woberekera. Kupitiliza kuvomerezedwa ndi chiwonetsero chovomerezeka cha acalabrutinib pambuyo pake kumatha kudalira kutsimikizika kopitilira ndikulongosola za chithandizo chazachipatala m'mayesero osokoneza.

Kuphatikiza apo, a FDA adapereka mankhwalawa Kukambitsirana Koyambirira ndi Njira Yothandizira Therapy. Inalandiranso dzina la Orphan Drug, lomwe limapereka chilimbikitso chothandizira ndikulimbikitsa kupanga mankhwala osokoneza bongo. Pakadali pano, mayeso opitilira 35 azachipatala m'maiko 40 omwe ali ndi odwala opitilira 2500 akuchitika kapena amalizidwa kuti apitilize kafukufuku kuti amvetsetse ndikuwonjezera kugwiritsa ntchito kwa acalabrutinib 5.

 

Acalabrutinib Reviews

Acalabrutinib (CAS:1420477-60-6), yomwe imagulitsidwa pansi pa dzina la Calquence® ku US ndi Canada, ndi m'badwo wachiwiri wa molekyulu yaying'ono yoletsa Bruton's tyrosine kinase (BTK). Pakulamula pakamwa, acalabrutinib imamangiriza komanso imalepheretsa zochitika za BTK zomwe zimalepheretsa kuyambitsa kwa B-cell ndikuwonetsa kwa B-cell Izi zimabweretsa kuletsa kukula kwa maselo oyipa a B omwe amapitilira BTK. BTK imafunika pakuwonetsa B-cell, imagwira gawo lalikulu pakusintha kwa B-cell, ndipo imakhudzidwa kwambiri ndi zoyipa zingapo za B-cell, kuphatikiza CLL / SLL. Kufotokozera kwa BTK m'maselo otupa kumalumikizidwa ndi kuchuluka ndikukula. Monga m'badwo wachiwiri wa BTK inhibitor, acalabrutinib idapangidwa kuti ikulitse mphamvu ku BTK ndikuchepetsa zochitika zomwe sizikuyenda bwino pa TEC (Tec Protein Tyrosine Kinase), EGFR (epidermal growth factor receptor), ndi ITK (interleukin-2-inducible T- selo kinase). Mbadwo woyamba wa BTK inhibitor, ibrutinib (Imbruvica), ulibe izi zomwe zimabweretsa mavuto ambiri. Kuphatikiza pa CLL / SLL, acalabrutinib imavomerezedwa ku Mantle Cell Lymphoma (MCL). Malangizo a National Cancer Center Network (NCCN) amalembetsa acalabrutinib wokhala ndi obinituzumab kapena woyamba kugwiritsa ntchito mankhwala a CLL / SLL komanso oyenera kugwiritsiridwa ntchito mu RL R / R).

 

Acalabrutinib Chithandizo (Chogwiritsidwa ntchito)

Acalabrutinib imagwiritsidwa ntchito pochizira anthu omwe ali ndi mantle cell lymphoma (MCL; khansa yomwe ikukula mwachangu yomwe imayamba m'maselo amthupi) omwe amathandizidwa kale ndi mankhwala amodzi amodzi.

Acalabrutinib imagwiritsidwa ntchito yokha kapena ndi obinutuzumab (Gazyva) kuchiza aakulu lymphocytic khansa ya m'magazi (CLL; mtundu wa khansa womwe umayambira m'maselo oyera a magazi) ndi ma lymphocytic lymphoma (SLL: mtundu wa khansa zomwe zimayambira m'maselo oyera a magazi).

Acalabrutinib ali mgulu la mankhwala otchedwa kinase inhibitors. Zimagwira ntchito poletsa ntchito ya mapuloteni osadziwika omwe amawonetsa kuti ma cell a khansa achulukane. Izi zimathandiza kuletsa kufalikira kwa maselo a khansa.

 

Acalabrutinib Njira Of AChtion

Mantle Cell Lymphoma (MCL) ndi mtundu wosavuta koma wowopsa wa B-cell non-Hodgkin lymphoma (NHL) wosazindikira. Pambuyo pake, kubwereranso kumakhala kofala kwa odwala a MCL ndipo pamapeto pake kumayimira kukula kwa matenda.

Lymphoma imachitika ma lymphocyte amthupi amakula ndikuchulukirachulukira. Ma lymphocyte a khansa otere amatha kupita mbali zambiri za thupi, kuphatikiza ma lymph node, ndulu, mafupa, magazi, ndi ziwalo zina zomwe zimatha kuchulukana ndikupanga chotupa. Mmodzi mwa mitundu yayikulu ya ma lymphocyte omwe amatha kukhala khansa yam'mimba ndi ma B-lymphocyte (B-cell) amthupi.

Bruton Tyrosine Kinase (BTK) ndi molekyulu yosonyeza ya B-cell antigen receptor ndi cytokine receptor pathways. Kusindikiza kwa BTK kotere kumapangitsa kuyambitsa njira zofunikira pakuchulukitsa kwa B-cell, kugulitsa, chemotaxis, ndi kumatira.

Acalabrutinib ndi tinthu tating'onoting'ono toletsa BTK. Onse acalabrutinib ndi metabolite yake yogwira ntchito, ACP-5862, amapanga mgwirizano wolimba ndi zotsalira za cysteine ​​(Cys481) patsamba logwira ntchito la BTK, zomwe zimapangitsa kuti ntchito ya BTK enzymatic iwonongeke. kuwonetsa mapuloteni CD86 ndi CD69, omwe pamapeto pake amaletsa kuchuluka kwakupha kwa B-cell ndikupulumuka.

Pomwe ibrutinib amadziwika kuti ndi woyamba-kalasi BTK inhibitor, acalabrutinib amawerengedwa kuti ndi m'badwo wachiwiri wa BTK inhibitor makamaka chifukwa amawonetsa kusankha kwambiri komanso kuletsa zomwe zikulimbana ndi BTK pomwe ali ndi IC50 yayikulu kwambiri kapenanso popanda choletsa chilichonse pa kinase zochitika za ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC, ndi YES1.

Mwakutero, acalabrutinib idapangidwa mwanzeru kuti ikhale yamphamvu kwambiri komanso yosankha kuposa ibrutinib, nthawi yonseyi ikuwonetsa zovuta zochepa - poganiza - chifukwa cha kuchepa kwa mankhwalawa.

AASraw ndiye katswiri wopanga Acalabrutinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Kodi zotsatira zoyipa za Acalabrutinib ndi ziti?

Acalabrutinib ingayambitse mavuto ena, kuphatikizapo:

Matenda opatsirana amatha kuchitika mukamamwa mankhwala ndi Acalabrutinib ndipo amatha kufa. Wothandizira zaumoyo wanu akhoza kukupatsani mankhwala ena ngati muli pachiwopsezo chotenga matenda. Uzani wothandizira zaumoyo wanu nthawi yomweyo ngati muli ndi zizindikilo za matenda, kuphatikiza malungo, kuzizira, kapena zizindikilo zonga za chimfine.

Mavuto a magazi (kukha magazi) atha kuchitika mukamalandira mankhwala ndi Acalabrutinib ndipo amatha kukhala owopsa ndipo atha kufa. Kuopsa kwanu kotuluka magazi kumatha kukulirakulira mukamamwa mankhwala ochepetsa magazi. Uzani wothandizira zaumoyo wanu ngati muli ndi zizindikilo zakutuluka magazi, kuphatikiza magazi m'mipando yanu kapena ndowe zakuda (zikuwoneka ngati phula), mkodzo wapinki kapena wabulauni, kutuluka mwadzidzidzi kapena kutuluka mwazi koopsa kapena komwe simungathe kuletsa, kusanza magazi kapena kusanza Zikuwoneka ngati malo a khofi, kutsokomola magazi kapena magazi, chizungulire, kufooka, kusokonezeka, malankhulidwe anu, kupweteka mutu komwe kumatenga nthawi yayitali, kapena kuvulaza kapena khungu lofiira kapena lofiirira

Kuchepetsa kuchuluka kwa maselo amwazi. Kuchepetsa magazi (maselo oyera, ma platelets, ndi maselo ofiira ofiira) ndizofala ndi Acalabrutinib, koma amathanso kukhala owopsa. Wothandizira zaumoyo wanu ayenera kuyesa magazi kuti aone kuchuluka kwa magazi anu nthawi zonse mukamalandira chithandizo cha Acalabrutinib.

Khansa yoyamba yachiwiri. Khansa yatsopano yachitika mwa anthu akamalandira chithandizo cha Acalabrutinib, kuphatikiza khansa yapakhungu kapena ziwalo zina. Wothandizira zaumoyo wanu adzakuyang'anirani khansa yapakhungu mukamamwa mankhwala ndi Acalabrutinib. Gwiritsani ntchito kuteteza dzuwa mukakhala kunja kwa dzuwa.

Mavuto amtundu wamtima (atrial fibrillation ndi atrial flutter) zachitika mwa anthu omwe amathandizidwa ndi Acalabrutinib. Uzani wothandizira zaumoyo wanu ngati muli ndi izi:

Zotsatira zofala kwambiri za Acalabrutinib zimaphatikizapo kupweteka mutu, kutsekula m'mimba, kupweteka kwa minofu ndi mafupa, matenda opatsirana opuma, ndi mabala.

Izi sizotsatira zonse za Acalabrutinib. Itanani dokotala wanu kuti akupatseni upangiri wa zamankhwala za zovuta zina. Mutha kunena za FDA ku 1-800-FDA-1088.

 

Acalabrutinib

 

 

Acalabrutinib VS Anayankha

BTK imagwira gawo lofunikira panjira yosonyeza njira ya B-cell; acalabrutinib imamangiriza mosasinthika ku BTK ndipo imalepheretsa zochitika zake. Mankhwalawa adapangidwa kuti azikhala osankha BTK inhibitor, poyesera kuchepetsa zina mwaziwopsezo zochepetsera zomwe zimawonedwa ndi ibrutinib. Malinga ndi a Dr. Brown, "Acalabrutinib ndiye choletsa BTK kusankha anthu omwe ali ndi comorbidities, makamaka mavuto amtima."

Zambiri zogwira ntchito zimawoneka chimodzimodzi pakati pa acalabrutinib ndi ibrutinib, ngakhale kutsata kwanthawi yayitali ndi ibrutinib, a Dr Brown adapitiliza. Chifukwa chake, kusiyana kwakukulu pakati pa mankhwalawa kumangokhala pazotsatira zawo. Ibrutinib nthawi zambiri imalekerera odwala okalamba ndipo imalumikizidwa ndimatenda ambiri am'magazi komanso kuthamanga kwa magazi. "Acalabrutinib imaloledwa bwino [kuposa ibrutinib], chifukwa chake ndimayigwiritsa ntchito mosakondera, makamaka kwa odwala anga okalamba," adatero.

Kuvomerezedwa kwa mankhwalawa ku CLL, komwe kudaperekedwa mu Novembala 2019, kudakhazikitsidwa potengera zachitetezo komanso zothandiza kuchokera pakufufuza kwakanthawi koyeserera kwa ELEVATE-TN kwa odwala omwe anali asanachiritsidwe CLL komanso kuyesedwa kwa ASCEND kwa odwala omwe abwerera m'mbuyo kapena osasunthika a CLL m'mayesero onsewa, acalabrutinib adawonetsa kupulumuka kopanda kupita patsogolo poyerekeza ndi mankhwala wamba, komanso mbiri yabwino yolekerera. M'mayesero a ELEVATE-TN, makamaka, acalabrutinib ophatikizidwa ndi obinutuzumab ndipo monga monotherapy adachepetsa kufalikira kwa matenda kapena kufa ndi 90% ndi 80%, motsatana.

"Kuleza mtima kumakhalabe vuto pankhani yothandizidwa ndi CLL, yomwe ingafune chithandizo chamankhwala kwa zaka zambiri," atero a Jeff Sharman, MD, Director of Research ku Willamette Valley Cancer Institute, Medical Director of Hematology Research for The US Oncology Network, komanso wolemba wamkulu pamilandu ya ELEVATE-TN, atolankhani. "M'mayeso a ELEVATE-TN ndi ASCEND kuyerekezera [acalabrutinib] ndi mankhwala omwe amagwiritsidwa ntchito kwambiri, [acalabrutinib] adawonetsa kusintha kwamankhwala mosadukiza kwa odwala m'malo osiyanasiyana, ndikupitilizabe kulolerana komanso chitetezo."

 

Kafukufuku: Acalabrutinib Pochiza Matenda a lymphocytic leukemia (CLL)  

(1) Matenda a lymphocytic leukemia (CLL)

Matenda a lymphocytic leukemia (CLL), khansa yodziwika bwino kwambiri ya khansa ya m'magazi, ndi chotupa cha clonal chopangidwa ndimaselo ang'onoang'ono okhwima a monomorphic omwe amaphatikizira CD5 ndi CD23. Chithandizo cha CLL chasintha kwambiri mzaka zaposachedwa. Mankhwala omwe amalimbana ndi mapuloteni mu njira ya B cell antigen receptor (BCR), monga ibrutinib, awonetsa kusintha pakukula kwaulere komanso kupulumuka konse, kuphatikiza odwala omwe ali ndi matenda oopsa. Ngakhale mankhwalawa asinthiratu mankhwalawa kwa odwala omwe ali ndi CLL, kuwonekera kwa mankhwala ndi mphamvu yake ndi ibrutinib kumatha kuchepa chifukwa chazotsatira zoyipa komanso zoopsa zokhudzana ndi mankhwala. Acalabrutinib, m'badwo wachiwiri komanso wosankha Bruton's tyrosine kinase (BTK) inhibitor, adapangidwa kuti athe kuchita bwino pochepetsa zochitika zoyipa zomwe zimakhudzana ndi ibrutinib zomwe zimaganiziridwa kuti ndizachiwiri pazotsatira za ibrutinib. Kuwunikaku kufotokozera mwachidule za chitukuko, kuwunika koyambirira kwa zamankhwala, komanso mayesero ofunikira pachipatala omwe awonetsa momwe acalabrutinib ali ndi mphamvu komanso poizoni ku CLL.

 

(2) Maphunziro a Preclinical a Acalabrutinib mu CLL

Kafukufuku wambiri wamankhwala osokoneza bongo adawonetsa mphamvu ya acalabrutinib pa choletsa cha BTK. Atayesedwa pamwazi wathunthu wamunthu, acalabrutinib anali ndi zida zopewera za BTK poyerekeza ndi ibrutinib. Ibrutinib idapezeka kuti imayambitsa kuchuluka kwa apoptosis yama cell a CLL poyerekeza ndi acalabrutinib, yomwe imatha kufotokozedwa ndi zomwe ibrutinib idachita. Acalabrutinib sinakhudze kwenikweni maselo amtundu wa T chifukwa chakusankha kwake poyerekeza ndi ibrutinib.

Zotsatira zotsutsana ndi zotupa za acalabrutinib zidawunikidwa pamitundu iwiri ya murine CLL: mtundu wa TCL1 wololeza komanso mtundu wa anthu wa CLL. Acalabrutinib adawonetsedwa kuti amaletsa kuwonetsa kwa BCR ndikuchiza ndi acalabrutinib kumalumikizidwa ndikuwonjezeka kwakukulu pakupulumuka poyerekeza ndi mbewa zosagwidwa (masiku 81 apakati vs masiku 59, p = 0.02). Acalabrutinib inachititsanso kuchepa kwakukulu kwa maselo omwe akuchulukirachulukira komanso chotupa chonse mumtambo.

Kuyanjana kwa Acalabrutinib ndi anti-CD20 monoclonal antibodies kuyesedwanso. Ibrutinib itha kusokoneza njira zingapo zama anti-CD20 anti-CD20 makamaka zoletsa ma cytotoxicity omwe amadalira ma antibody ndi phagocytosis yomwe ingachepetse mphamvu yawo yotsutsana ndi chotupa. ndipo anapeza kuti sizinasokoneze njirazi, mwina chifukwa chazovuta zochepa za acalabrutinib.Ngakhale kuphatikiza kwa acalabrutinib ndi anti-CD2 monoclonal antibody sikunaphunzire mu vivo modelo, gawo lachiwiri 3 Kafukufuku wa 20 akupitilira kapena akwaniritsidwa omwe akuwonetsa kugwira ntchito kwa acalabrutinib kuphatikiza ndi anti-CDXNUMX monoclonal antibody.

Kuphatikiza kwina kwa acalabrutinib kwawerengedwa mu ma vitro komanso mitundu ya vivo. Acalabrutinib idaphatikizidwa ndi PI3Kdelta inhibitor (ACP-319) mumtundu wa murine CLL ndikuwonetsa kuchepa kwakukulu kwa kuchuluka kwa chotupa, kuwonetsa NF-KB ndikuwonetsa BCL-xL ndi MCL-1 poyerekeza ndi monotherapy. osalemba nawo mayesero azachipatala adathandizidwa ndi acalabrutinib ndi venetoclax.Phatikizidwe ili lidawonetsedwa kuti lachulukitsa apoptosis poyerekeza ndi mankhwala okhawo, kuwonetsa ubale wolumikizana wofanana ndi womwe umawonedwa ndi ibrutinib ndi venetoclax. Kuyesa kwotsatira kwa vivo kunawonetsa kupulumuka kwakanthawi mu mbewa zochitidwa ndi onse acalabrutinib ndi venetoclax poyerekeza ndi mankhwala okha.

 

(3) Mawuwo

Mwachidule, kafukufuku wofotokozedwayo akuwonetsa kuti acalabrutinib ili ndi mphamvu zambiri pochizira CLL, onse omwe ali ndi chithandizo cha naïve komanso obwezeretsanso. Sizikudziwika ngati magwiridwe antchito ndi ofanana kapena apamwamba kuposa ibrutinib ndipo maphunziro akupitilirabe poyesa kufananizira awa. Ngakhale zoopsa zoyipa zomwe zimakhudzana ndi BTK monga kutuluka magazi kapena zochitika zamatenda a atrial sizimachitika kawirikawiri, acabrutinib Ali ndi mbiri yapadera ya AE, makamaka mutu, womwe umafunikira kuwunika mosamala ndi ukadaulo woyang'anira. Zambiri zamaphunziro omwe akuchitika omwe akuwunika kuphatikiza ndi acalabrutinib zithandizira kufotokozera ntchito yake pakuwongolera CLL. Pomaliza, ndikuvomerezedwa ndi FDA, zochitika zenizeni ndi acalabrutinib zithandizira kufotokozera zamtundu wa kawopsedwe.

AASraw ndiye katswiri wopanga Acalabrutinib.

Chonde dinani apa kuti mumve zambiri: Ochezera ife

 

Reference

[1] Ulamuliro wa Zakudya ndi Mankhwala ku US. Project Orbis: FDA ivomereza acalabrutinib ya CLL ndi SLL. Ipezeka pa https://www.fda.gov/drugs/resource-information-approved-drugs/project-orbis-fda-approves-acalabrutinib-cll-and-sll. Idapezeka pa Epulo 29, 2020.

[2] Sharman JP, Banerji V, Fogliatto LM, ndi al. ELEVATE-TN: Gawo lachitatu la kafukufuku wa acalabrutinib wophatikizidwa ndi obinutuzumab kapena yekha vs obinutuzumab kuphatikiza chlorambucil mwa odwala omwe alibe mankhwala a lymphocytic leukemia. Magazi 3; 2019 (suppl 134): 1.

[3] Kutulutsa kwa AstraZeneca. Calquence yovomerezeka ku US kwa odwala achikulire omwe ali ndi khansa ya m'magazi ya lymphocytic. Ipezeka pa https://www.astrazeneca.com/media-centre/press-releases/2019/calquence-approved-in-the-us-for-adult-patients-with-chronic-lymphocytic-leukaemia-21112019.html. Idapezeka pa Epulo 29, 2020.

[4] Goede V, Fischer K, Busch R, ndi al. Obinutuzumab kuphatikiza chlorambucil mwa odwala omwe ali ndi CLL komanso zinthu zomwe zikupezeka. N Engl J Med. 2014; 370 (12): 1101-1110. onetsani: 10.1056 / NEJMoa1313984.

[5] Parikh SA, Muchtar E, Laplant B, ndi al. Kafukufuku wachiwiri wowerengera poyerekeza acalabrutinib kapena obinutuzumab pochiza odwala omwe ali pachiwopsezo cha matenda a Chronic Lymphocytic Leukemia (CLL) kapena Small Lymphocytic Lymphoma (SLL). Magazi. 2; 2019 (Wothandizira_134): 1. onetsani: 4306 / magazi-10.1182-2019.

[6] (Adasankhidwa) Covey T, Gulranjani M, Cheung J, et al. Pharmacodynamic kuyesa kwa acalabrutinib mwa odwala omwe abwereranso / obwezera komanso osachiritsira omwe ali ndi matenda a Chronic Lymphocytic Leukemia (CLL) mu gawo la 1/2 ACE-CL-001 Study. Magazi. 2017; 130 (Wowonjezera1): 1741. onetsani: 10.1182 / magazi.V130.Suppl_1.1741.1741.

[7] Byrd JC, Brown JR, O'Brien S, ndi al. Ibrutinib motsutsana ndi ofatumumab omwe amathandizidwa kale ndi khansa ya m'magazi. N Engl J Med. 2014; 371 (3): 213–223. onetsani: 10.1056 / NEJMoa1400376.

[8] Woyach JA, Bojnik E, Ruppert AS, ndi al. Ntchito ya Bruton's tyrosine kinase (BTK) ndiyofunikira pakukula ndikukula kwa matenda a khansa ya m'magazi (CLL). Magazi. 2014; 123 (8): 1207-1213. onetsani: 10.1182 / magazi-2013-07-515361.

[9] Chiorazzi N, Rai KR, Ferrarini M. Matenda a m'magazi a lymphocytic. N Engl J Med. 2005; 352 (8): 804-815. onetsani: 10.1056 / NEJMra041720.

[10] Wopambana PM, Robak T, Owen C, et al. Kukhazikika kolimba komanso kutsata mwatsatanetsatane kwa mankhwala oyamba a ibrutinib kwa odwala okalamba omwe ali ndi khansa ya m'magazi yayitali: gawo lowonjezera la 3 kuchokera ku RESONATE-2. Haematologica. 2018; 103 (9): 1502-1510. onetsani: 10.3324 / haematol.2018.192328.

[11] Herman SEM, Montraveta A, Niemann CU, ndi al. Bruton Tyrosine Kinase (BTK) inhibitor ACP-196 ikuwonetsa zochitika zamankhwala m'magulu awiri a mbewa za khansa ya m'magazi ya lymphocytic. Magazi. 2015; 126 (23): 2920. onetsani: 10.1182 / magazi.V126.23.2920.2920.

 

 

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