Lithethefatsi tse Khahlanong le Kankere Acalabrutinib: Phekolo ea CLL / SLL / MCL - AASraw
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Lithethefatsi tse Khahlanong le Kankere Acalabrutinib

 

  1. Acalabrutinib Boikhohomoso
  2. Litlhahlobo tsa Acalabrutinib
  3. Phekolo ea Acalabrutinib (E sebelisetsoa)
  4. Mokhoa oa Ketso oa Acalabrutinib
  5. Litla-morao tse ka bang teng tsa Acalabrutinib ke life?
  6. Acalabrutinib VS Ibrutinib
  7. Patlisiso: Acalabrutinib Ho Phekola Lefuemia e sa Foleng ea lymphocytic (CLL)

 

Acalabrutinib Boikhohomoso

Ho fihlela joale, acalabrutinib e sebelisitsoe litekong tsa ho ithuta kalafo ea B-All, Myelofibrosis, Ovarian Cancer, Multiple Myeloma le Hodgkin Lymphoma, hara tse ling.

Ho tloha ka la 31 Mphalane, 2017, FDA e amohetse Astra Zeneca e laoloang ka molomo Calquence (acalabrutinib). Bruton Tyrosine Kinase (BTK) inhibitor e bontšitse kalafo ea lefu le sa foleng la lymphocytic leukemia, lymphocytic lymphoma, le bakuli ba baholo ba nang le Mantle Cell Lymphoma (MCL) ba seng ba fumane bonyane kalafo e le 'ngoe ea pele.

E boetse e tsejoa e le EA-196-ACP, acalabrutinib e boetse e nkuoa e le moloko oa bobeli oa BTK inhibitor hobane e ne e entsoe ka mokhoa o utloahalang hore e be matla le ho khetha ho feta ibrutinib, eo ho nahanoang hore e lebelletsoe ho bonts'a litlamorao tse fokolang ka lebaka la ho fokotsa litlamorao tsa ba emelang liphofu ntle le BTK.

Leha ho le joalo, acalabrutinib e ile ea amoheloa tlasa tsela ea tumello e potlakileng ea FDA, e ipapisitseng le sekhahla sa karabelo le lithuso tse amohelang pejana meriana e phekolang maemo a tebileng kapa / le e tlatsang tlhoko ea bongaka e sa fihlelloang e ipapisitse le pheletso ea motho e mong. Kamohelo e tsoelang pele ea sesupo sa acalabrutinib se amoheloang ha joale e kanna ea itšetleha ka netefatso e tsoelang pele le tlhaloso ea melemo ea kliniki litekong tsa pherekano.

Ntle le moo, FDA e file meriana ena Tlhatlhobo ea Bohlokoa le Tlhatlhobo ea Therapy. E boetse e amohetse lebitso la Orphan Drug, le fanang ka likhothaletso ho thusa le ho khothaletsa nts'etsopele ea litlhare bakeng sa maloetse a sa tloaelehang. Nakong ena, liteko tse fetang 35 tsa kliniki ho pholletsa le linaha tse 40 tse nang le bakuli ba fetang 2500 li ntse li tsoela pele kapa li phethetsoe mabapi le lipatlisiso tse ling tsa kutloisiso e ntlafetseng le ho holisa ts'ebeliso ea kalafo ea acalabrutinib 5.

 

Acalabrutinib Reviews

Acalabrutinib (CAS:1420477-60-6), e rekisoang tlasa lebitso la khoebo la Calquence® naheng ea Amerika le Canada, ke moloko oa bobeli oa molek'hule e nyane ea molek'hule ea Bruton's tyrosine kinase (BTK). Ha o tsamaisa ka molomo, acalabrutinib e tlama le ho thibela ts'ebetso ea BTK e thibelang ts'ebetso ea B-cell le lets'oao la B-cell. Ketso ena e lebisa ho thibelo ea kholo ea lisele tse kotsi tsa B tse fetelletseng BTK. BTK e hlokahala bakeng sa lets'oao la B-cell, e bapala karolo ea bohlokoa ho butsoang ha B-cell, mme e hatelloa haholo ho bongata ba lisele tsa B-cell, ho kenyeletsoa CLL / SLL. Polelo ea BTK ka lisele tsa hlahala e amahanngoa le keketseho ea ho ata le ho phela. E le moloko oa bobeli oa BTK inhibitor, acalabrutinib e ne e etselitsoe ho eketsa phello ho BTK le ho fokotsa ts'ebetso ea sepheo sa TEC (Tec Protein Tyrosine Kinase), EGFR (epidermal growth factor receptor), le ITK (interleukin-2-inducible T- seleng kinase). Moloko oa pele oa BTK inhibitor, ibrutinib (Imbruvica), ha e na mofuta ona o lebisang liphellong tse phahameng tsa litlamorao. Ntle le CLL / SLL, acalabrutinib e lumelloa bakeng sa Mantle Cell Lymphoma (MCL). Tataiso ea Setsi sa Kankere ea Naha (NCCN) e thathamisa acalabrutinib ka obinituzumab kapa ntle le eona e le kalafo ea mohala oa pele bakeng sa CLL / SLL hape e nepahetse bakeng sa ts'ebeliso ea CLL e khutlileng kapa e sa sebetseng.

 

Acalabrutinib Kalafo (E sebelisetsoa)

Acalabrutinib e sebelisetsoa ho alafa batho ba nang le mantle cell lymphoma (MCL; mofets'e o hola ka potlako o qalang liseleng tsa sesole sa 'mele) ba seng ba ntse ba alafshoa bonyane meriana e le' ngoe ea chemotherapy.

Acalabrutinib e sebelisoa e le mong kapa ka obinutuzumab (Gazyva) ho phekola phekolo e sa foleng ea "lymphocytic leukemia" (CLL; mofuta oa mofets'e o qalang ka lisele tse tšoeu tsa mali) le lymphocytic lymphoma (SLL: mofuta oa tsoaroa ke kankere e qalang ka lisele tse tšoeu tsa mali).

Acalabrutinib e sehlopheng sa meriana e bitsoang kinase inhibitors. E sebetsa ka ho thibela ts'ebetso ea protheine e sa tloaelehang e bonts'ang lisele tsa mofetše ho ngatafala. Sena se thusa ho emisa ho ata ha lisele tsa mofetše.

 

Acalabrutinib Mekhenike Of Amotsoako

Mantle Cell Lymphoma (MCL) ke mofuta o sa tloaelehang empa o le mabifi oa B-cell non-Hodgkin lymphoma (NHL) e nang le ts'oaetso e mpe. Kamora moo, ho khutlela morao ho atile ho bakuli ba MCL mme qetellong ho emela tsoelo-pele ea mafu.

Lymphoma e hlaha ha li-immune lymphocyte li hola 'me li ngatafala ka mokhoa o sa laoleheng. Li-lymphocyte tse nang le mofetše li ka ea likarolong tse ngata tsa 'mele, ho kenyeletsoa li-lymph node, spleen, mokong oa masapo, mali le litho tse ling moo li ka ikatisang' me tsa etsa bongata bo bitsoang hlahala. E 'ngoe ea mefuta ea mantlha ea li-lymphocyte e ka bang le lymphomas tse nang le mofetše ke li-B-lymphocyte tsa' mele (B-cell).

Bruton Tyrosine Kinase (BTK) ke molek'hule e tšoaeang ea B-cell antigen receptor le cytokine receptor pathways. Ts'oaetso e joalo ea BTK e baka ts'ebetso ea litselana tse hlokahalang bakeng sa keketseho ea B-cell, thekiso ea khoebo, chemotaxis le khokahano.

Acalabrutinib ke molek'hule e nyane ea inhibitor ea BTK. Ka bobeli acalabrutinib le metabolite ea eona e sebetsang, ACP-5862, e sebetsa ho theha maqhama a kopaneng le masala a cysteine ​​(Cys481) sebakeng sa BTK se sebetsang, se lebisang ho thibelo ea ts'ebetso ea enzymatic ea BTK. ho saena liprotheine CD86 le CD69, tse qetellang li thibela ho ata ha B-cell le ho phela.

Le ha ibrutinib e tsejoa e le sebui sa pele sa sehlopha sa BTK, acalabrutinib e nkuoa e le moloko oa bobeli oa BTK inhibitor haholo hobane e bonts'a khetho e phahameng le thibelo ea tšebetso e shebiloeng ea BTK ha e ntse e na le IC50 e kholo kapa ha ho na thibelo ho eona. kinase ea ITK, EGFR, ERBB2, ERBB4, JAK3, BLK, FGR, FYN, HCK, LCK, LYN, SRC le YES1.

Ha e le hantle, acalabrutinib e ne e etselitsoe hore e be matla le ho khetha ho feta ibrutinib, ha e ntse e le teng e bonts'a litlamorao tse fokolang - ka mohopolo - ka lebaka la litlamorao tsa setlhare.

AASraw ke moetsi oa litsebi oa Acalabrutinib.

Ka kopo tlanya mona bakeng sa tlhaiso-leseling e qotsitsoeng: Lethathamo la rona

 

Litla-morao tse ka bang teng tsa Acalabrutinib ke life?

Acalabrutinib e ka baka litla-morao tse tebileng, ho kenyelletsa:

Ts'oaetso e matla e ka etsahala nakong ea kalafo le Acalabrutinib mme e ka lebisa lefung. Mofani oa hao oa tlhokomelo ea bophelo a ka u fa meriana e itseng haeba u na le kotsi e kholo ea ho fumana tšoaetso. Bolella mofani oa tlhokomelo ea bophelo hang-hang haeba u na le matšoao a tšoaetso, ho kenyelletsa feberu, ho bata, kapa matšoao a kang a sefuba.

Mathata a tsoang mali (hemorrhage) a ka etsahala nakong ea kalafo le Acalabrutinib mme a ka ba kotsi mme a ka lebisa lefung. Monyetla oa ho tsoa mali o ka eketseha haeba o noa moriana o fokolang mali. Bolella mofani wa tlhokomelo ya bophelo haeba o na le matshwao a ho tswa madi, ho kenyeletswa madi mantle a hao kapa mantle a matsho (a shebahala jwaloka sekontiri), moroto o mopinki kapa o sootho, ho tswa madi ho sa lebellwang kapa ho tswa madi ho hoholo kapa o sa kgone ho a laola, hlatsa madi e shebahala joalo ka mabala a kofi, ho khohlela mali kapa maqeba a mali, ho tsekela, bofokoli, pherekano, liphetoho puong ea hao, ho opeloa ke hlooho e tšoarellang nako e telele, kapa ho longoa kapa matheba a bofubelu kapa a pherese

Fokotseha lipalo tsa lisele tsa mali. Ho fokotseha ha lipalo tsa mali (lisele tse tšoeu tsa mali, liplatelete, le lisele tse khubelu tsa mali) li tloaelehile ka Acalabrutinib, empa le tsona li ka ba matla. Mofani oa hao oa tlhokomelo ea bophelo o lokela ho etsa liteko tsa mali ho lekola palo ea mali a hau khafetsa nakong ea kalafo le Acalabrutinib.

Kankere ea bobeli ea mantlha. Kankere e ncha e etsahetse ho batho nakong ea kalafo le Acalabrutinib, ho kenyeletsoa le mofetše oa letlalo kapa litho tse ling. Mofani oa hao oa tlhokomelo ea bophelo o tla u hlahloba bakeng sa mofetše oa letlalo nakong ea kalafo le Acalabrutinib. Sebelisa tšireletso ea letsatsi ha u le kantle khanyeng ea letsatsi.

Mathata a morethetho oa pelo (atrial fibrillation le atrial flutter) a etsahetse ho batho ba alafshoang ka Acalabrutinib. Bolella mofani oa tlhokomelo ea bophelo haeba u na le matšoao a latelang: ho otla ha pelo kapele kapa ho sa tloaelehang, ho tsekela, ho ikutloa u akhehile, ho se utloise bohloko sefubeng kapa ho hema hanyane.

Litla-morao tse tloaelehileng tsa Acalabrutinib li kenyelletsa hlooho, letšollo, bohloko ba mesifa le manonyeletso, tšoaetso e phahameng ea phefumoloho le matetetso.

Tsena ha se litla-morao tsohle tse ka bang teng tsa Acalabrutinib. Bitsa ngaka ea hau bakeng sa likeletso tsa bongaka ka litla-morao. U ka tlaleha litla-morao ho FDA ho 1-800-FDA-1088.

 

Acalabrutinib

 

 

Mofuta oa Acalabrutinib VS Ibrutinib

BTK e bapala karolo ea bohlokoa ho B-cell receptor signaling pathway; acalabrutinib e tlama e sa fetoheng ho BTK mme e thibela ts'ebetso ea eona. Moriana ona o ne o entsoe e le mokhoa o khethollang oa BTK inhibitor, ka boiteko ba ho fokotsa tse ling tsa chefo e thibelang kalafo eo hangata e bonoang ka ibrutinib. Ho ea ka Dr. Brown, "Acalabrutinib ke thibelo ea BTK ea khetho bakeng sa batho ba nang le comorbidities, haholo-holo mathata a pelo."

Boitsebiso bo sebetsang bo shebahala bo ts'oana lipakeng tsa acalabrutinib le ibrutinib, leha tatelano e le telele ho ibrutinib, Dr. Brown o tsoetse pele. Ka hona, phapang ea mantlha lipakeng tsa lithethefatsi e lutse maemong a litlamorao tsa tsona. Ibrutinib e atisa ho mamelloa hampe ho bakuli ba baholo mme e amahanngoa le sekhahla se phahameng sa mafura a atrial le khatello ea mali. "Acalabrutinib e mamelloa hamolemo haholo ho feta ibrutinib], ka hona ke e sebelisa ka khethollo, haholo ho bakuli ba ka ba baholo," o boletse joalo.

Kamohelo ea lithethefatsi ho CLL, e fuoeng ka Pherekhong 2019, e ne e ipapisitse le tlhaiso-leseling e sebetsang mabapi le ts'ebeliso ea nakoana ea nyeoe ea ELEVATE-TN ea bakuli ba neng ba sa alafshoa CLL le nyeoe ea ASCEND ea bakuli ba nang le CLL e neng e khutlile kapa e le morao. e bonts'itse pholoho e senang tsoelo-pele ha e bapisoa le kalafo e tloaelehileng, le boemo bo botle ba mamello. Tekong ea ELEVATE-TN, haholo-holo, acalabrutinib e kopantsoe le obinutuzumab mme joalo ka monotherapy e fokotsitse kotsi ea kholo ea mafu kapa lefu ka 90% le 80%, ka ho latellana.

"Ho mamelleha e ntse e le bothata maemong a kalafo a hajoale a CLL, a ka hlokang kalafo e tsoelang pele ka lilemo tse ngata," ho boletse Jeff Sharman, MD, Motsamaisi oa Patlisiso Willamette Valley Cancer Institute, Motsamaisi oa Bongaka oa Patlisiso ea Hematology bakeng sa The US Oncology Network, le mongoli ea etelletseng pele oa nyeoe ea ELEVATE-TN, tsebisong ea boralitaba. "Litekong tsa ELEVATE-TN le ASCEND tse bapisang [acalabrutinib] le mekhoa ea kalafo e sebelisoang khafetsa, [acalabrutinib] e bonts'itse ntlafatso e nang le moelelo ea bongaka ho pholoheng ntle le tsoelo-pele ho bakuli maemong a mangata, ha e ntse e boloka boemo ba eona bo mamellehang le polokeho."

 

Lipatlisiso: Acalabrutinib Ho Phekola Kankere ea tlhaho ea "lymphocytic leukemia" (CLL)  

(1) Kankere ea tlhaho ea "lymphocytic leukemia" (CLL)

Leukemia e sa foleng (CLL), leukemia e tloaelehileng haholo ho motho e moholo, ke lethopo le nang le clonal le entsoeng ka lisele tse nyane tse holileng tsebong tsa B tse kopanyang CD5 le CD23. Ponahalo ea kalafo ea CLL e fetohile haholo lilemong tsa morao tjena. Lithethefatsi tse lebisang liprotheine tseleng ea B cell antigen receptor (BCR), joalo ka ibrutinib, li bonts'itse ntlafatso ea tsoelo-pele e sa lefelloeng le ho phela ka kakaretso, ho kenyeletsoa le bakuli ba nang le mafu a kotsi haholo. Le ha lithethefatsi tsena li fetotse paradigm ea kalafo ho bakuli ba nang le CLL, ho pepeseha kalafo le ho ba matla le ibrutinib ho ka fokotsoa ka lebaka la boemo ba litla-morao le chefo e amanang le kalafo. Acalabrutinib, moloko oa bobeli le Bruton's tyrosine kinase (BTK) inhibitor, e ile ea ntlafatsoa ho ntlafatsa ts'ebetso ha e ntse e fokotsa liketsahalo tse mpe tse amanang le ibrutinib tseo ho nahanoang hore ke tsa bobeli ho litlamorao tsa ibrutinib. Tlhatlhobo ena e tla akaretsa nts'etsopele, tlhahlobo ea pele ho bongaka, le liteko tsa mantlha tsa bongaka tse bonts'itseng ts'ebetso ea acalabrutinib le chefo ho CLL.

 

(2) Lithuto tsa Preclinical tsa Acalabrutinib ho CLL

Liphuputso tse 'maloa tse entsoeng pele ho nako li bontšitse katleho ea acalabrutinib ho thibelo ea BTK. Ha e lekoa maling ohle a motho, acalabrutinib e ne e na le thibelo ea BTK ea equipotent ha e bapisoa le ibrutinib. Ibrutinib e fumanoe e baka ho eketseha ha apoptosis ea lisele tsa CLL ha e bapisoa le acalabrutinib, e ka hlalosoang ke litlamorao tsa ibrutinib. Acalabrutinib e bile le phello e fokolang ho lisele tsa T tse phetseng hantle mohlomong ka lebaka la khetho ea eona ha e bapisoa le ibrutinib.

Litlamorao tsa anti-tumor tsa acalabrutinib li ile tsa hlahlojoa ka mefuta e 'meli ea murine ea CLL: mofuta oa TCL1 oa phetisetso e amohelang le mofuta oa batho oa XL o fuoeng xenografted. Acalabrutinib e bonts'itsoe hore e thibela ho tšoaea ha BCR le kalafo ka acalabrutinib ho ne ho amahanngoa le keketseho e kholo ea pholoho ha e bapisoa le litoeba tse sa alafshoang (matsatsi a mahareng a 81 le matsatsi a 59, p = 0.02). Acalabrutinib hape e bakile phokotso e kholo ea lisele tse ntseng li eketseha le moroalo o felletseng oa hlahala lehloeng.

Ts'ebelisano ea Acalabrutinib le li-antibodies tsa anti-CD20 monoclonal le eona e se e hlahlobiloe. Ibrutinib e kanna ea kena-kenana le mekhoa e mengata ea ts'ebetso ea lithibela-mafu tse khahlanong le CD20 ka ho khetheha e thibelang cytotoxicity ea cellular e itšetlehileng ka antibody le phagocytosis e ka fokotsang phello ea eona e khahlanong le hlahala.Golay et al o hlahlobile litlamorao tsa acalabrutinib ho cytotoxicity e itšetlehileng ka antibody le phagocytosis mme a fumana hore ha e kena-kenane le lits'ebetso tsena, mohlomong ka lebaka la litlamorao tse fokolang tsa sepheo sa acalabrutinib. Le ha motswako oa acalabrutinib le anti-CD20 monoclonal antibody ha e so ka e ithutoa ka mofuta oa vivo, karolo ea 2 le karolo Liphuputso tse 3 li ntse li tsoela pele kapa li se li phethetsoe tse bonts'ang katleho ea acalabrutinib hammoho le anti-CD20 monoclonal antibody.

Metsoako e meng ea acalabrutinib e ithutiloe ka in vitro le in vivo models. Acalabrutinib e ne e kopantsoe le PI3Kdelta inhibitor (ACP-319) ka mofuta oa murine CLL mme e bonts'a phokotso e kholo ea ho ata ha hlahala, ho saena ha NF-KB le polelo ea BCL-xL le MCL-1 ha e bapisoa le monotherapy. Motsoako ona o bontšitsoe o eketsehile apoptosis ha o bapisoa le moriana o le mong, ho fana ka maikutlo a kamano e ts'oanang le e bonoang le ibrutinib le venetoclax. Teko e latelang ea vivo e bonts'itse ho phela ha nako e telele ho litoeba tse tšoaroang ka bobeli ba acalabrutinib le venetoclax ha li bapisoa le sethethefatsi se le seng.

 

(3) Nahanisisa

Ka kakaretso, lithuto tse hlalositsoeng li bonts'a hore acalabrutinib e na le katleho e kholo kalafong ea CLL, kalafo ea naïve le ho khutlela morao hape. Ha ho hlake hore na ts'ebetso e lekana kapa e phahametse ibrutinib mme lithuto li ntse li tsoela pele ho leka ho bapisa mahlahana ana. Le ha chefo e amanang le BTK ea khale joalo ka ho tsoa mali kapa liketsahalo tsa mafura a atrial e le liketsahalo tse sa tloaelehang, acalabrutinib e na le boemo bo ikhethileng ba AE, haholo hlooho ea hlooho, e hlokang ho lekoa ka hloko le boiphihlelo tsamaisong. Lintlha tse tsoang liphuputsong tse tsoelang pele tsa ho lekola metsoako le acalabrutinib li tla thusa ho hlakisa karolo ea eona tsamaisong ea CLL. Kamora nako, ka tumello ea FDA, boiphihlelo ba 'nete ba lefats'e ka acalabrutinib bo tla thusa ho ntlafatsa botumo ba chefo.

AASraw ke moetsi oa litsebi oa Acalabrutinib.

Ka kopo tlanya mona bakeng sa tlhaiso-leseling e qotsitsoeng: Lethathamo la rona

 

Reference

[1] Tsamaiso ea Tsamaiso ea Lijo le Lithethefatsi ea US. Project Orbis: FDA e amohela acalabrutinib bakeng sa CLL le SLL. E fumaneha ho https://www.fda.gov/drugs/resource-information-approved-drugs/project-orbis-fda-approves-acalabrutinib-cll-and-sll. E fihlile ka la 29 Mmesa, 2020.

[2] Sharman JP, Banerji V, Fogliatto LM, le al. ELEVATE-TN: Karolo ea 3 ea thuto ea acalabrutinib e kopantsoe le obinutuzumab kapa e le 'ngoe vs obinutuzumab hammoho le chlorambucil ho bakuli ba nang le leukemia e sa foleng ea lymphocytic. Mali 2019; 134 (suppl 1): 31.

[3] Phatlalatso ea AstraZeneca. Calquence e amoheloa US bakeng sa bakuli ba baholo ba nang le kankere ea mali e sa foleng ea lymphocytic E fumaneha ho https://www.astrazeneca.com/media-centre/press-releases/2019/calquence-approved-in-the-us-for-adult-patients-with-chronic-lymphocytic-leukaemia-21112019.html. E fihlile ka la 29 Mmesa, 2020.

[4] Goede V, Fischer K, Busch R, le al. Obinutuzumab hammoho le chlorambucil ho bakuli ba nang le CLL le maemo a teng. N Engl J Med. 2014; 370 (12): 1101–1110. doi: 10.1056 / NEJMoa1313984.

[5] Parikh SA, Muchtar E, Laplant B, le al. Phuputso ea karolo ea 2 e sa sebetseng e bapisang acalabrutinib le obinutuzumab kapa ha e na kalafo ea kalafo ea bakuli ba kotsing e kholo ba nang le Chronic Lymphocytic Leukemia (CLL) kapa Small Lymphocytic Lymphoma (SLL). Mali. 2019; 134 (Tlatsetso_1): 4306. doi: 10.1182 / mali-2019-123824.

[6] Covey T, Gulranjani M, Cheung J, le al. Tlhatlhobo ea Pharmacodynamic ea acalabrutinib ho bakuli ba khutlang hape / ba sa sebetseng le ba kalafo ba nang le lefu la Chronic Lymphocytic Leukemia (CLL) mokhahlelong oa 1/2 ACE-CL-001. Mali. 2017; 130 (Tlatsetso1): 1741. doi: 10.1182 / mali.V130.Suppl_1.1741.1741.

[7] Byrd JC, Brown JR, O'Brien S, le al. Ibrutinib khahlanong le ofatumumab kalafong e sa foleng ea lymphoid leukemia. N Engl J Med. 2014; 371 (3): 213-223. doi: 10.1056 / NEJMoa1400376.

[8] Woyach JA, Bojnik E, Ruppert AS, le al. Mosebetsi oa Bruton's tyrosine kinase (BTK) o bohlokoa ntlafatsong le katolosong ea leukemia e sa foleng ea lymphocytic (CLL). Mali. 2014; 123 (8): 1207-1213. doi: 10.1182 / mali-2013-07-515361.

[9] Chiorazzi N, Rai KR, Ferrarini M. Lefuemia e sa foleng ea lymphocytic. N Engl J Med. 2005; 352 (8): 804-815. doi: 10.1056 / NEJMra041720.

[10] Tonakholo ea Barr, Robak T, Owen C, et al. Ts'ebetso e ts'oarellang le tlhaiso-leseling e felletseng ea kalafo ea kalafo ea ibrutinib ea pele ho bakuli ba baholo ba nang le kankere ea mali e sa foleng ea lymphocytic: sephetho se atolositsoeng sa 3 se tsoang ho RESONATE-2. Haematologica. 2018; 103 (9): 1502-1510. doi: 10.3324 / haematol.2018.192328.

[11] Herman SEM, Montraveta A, Niemann CU, le al. Bruton Tyrosine Kinase (BTK) inhibitor ACP-196 e bonts'a tšebetso ea bongaka mefuteng e 'meli ea toeba ea lefu la kankere ea mali e sa foleng ea lymphocytic. Mali. 2015; 126 (23): 2920. doi: 10.1182 / mali.V126.23.2920.2920.

 

 

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