Kalafo ea CAR-T e Hlōla Khakanyo e Mpe ho Lymphoma ea B-Cell ea Boemo bo Holimo
Phuputso ea morao tjena e phatlalalitsoeng ho Tsoelo-pele ea Malie senola hore phekolo ea lisele tsa CAR-T e fana ka melemo ea bohlokoa ea bongaka bakeng sa bakuli ba nang le maemo a holimo Lymphoma ea Lisele tsa B (HGBL), mofuta o mabifi haholo oa lymphoma e kholo ea B-cell (LBCL). Phuputso ea DESCAR-T LYSA, e entsoeng ke bafuputsi ba Mafora, e ne e shebane le bakuli ba fumaneng phekolo ea CAR-T e le phekolo ea mokhahlelo oa boraro kapa ho feta moo, ho kenyeletsoa le ba nang le MYC le BCL2 le/kapa BCL6 rearrangments—e tsejoang e le lymphoma ea "habeli-hit" kapa "triple-hit".
Phuputso e ngolisitse bakuli ba 228 ba tsoang ngolisong ea DESCAR-T ea Fora, bao ba 73 ba bona ba fumanoeng ba e-na le HGBL, ha ba 155 ba setseng ba ne ba e-na le LBCL e seng ea HGBL. Phuputso e ne e ikemiselitse ho lekola polokeho le katleho ea phekolo ea CAR-T lihlopheng tsena, ka nako e tloaelehileng ea ho latela ea likhoeli tse 18.5.
Liphuputso li senotse hore sekhahla sa karabelo ka kakaretso (ORR) le sekhahla sa karabelo e felletseng (CR) li ne li tšoana pakeng tsa bakuli ba HGBL le bao e seng ba HGBL, ho 68% le 60% bakeng sa HGBL, le 76% le 59% bakeng sa bao e seng ba HGBL, ka ho latellana (p=0.293 le p=0.923). Ho feta moo, ho pholoha ho se nang tsoelo-pele (PFS) ho bakuli ba HGBL e ne e le likhoeli tse 3.2, ha ho bapisoa le likhoeli tse 4.5 bakeng sa bakuli bao e seng ba HGBL, leha phapang ena e ne e se ea bohlokoa lipalo-palo (p=0.103). Ka ho tšoanang, sekhahla sa pholoho e akaretsang (OS) e ne e le likhoeli tse 15.4 bakeng sa bakuli ba HGBL ha ho bapisoa le likhoeli tse 18.3 bakeng sa bakuli bao e seng ba HGBL (p=0.214).
Hoa thahasellisa hore ha OS e baloa ho tloha ka letsatsi leo bakuli ba ileng ba tšoaneleha bakeng sa phekolo ea CAR-T ka lona, OS e mahareng bakeng sa bakuli ba HGBL e theohetse ho likhoeli tse 7.6, ha e bapisoa le likhoeli tse 11.8 bakeng sa bakuli bao e seng ba HGBL (p=0.062), e leng se bontšang hore nako ea tsamaiso ea CAR-T e bapala karolo ea bohlokoa ho ntlafatseng liphetho.
Har'a mefuta e fapaneng ea HGBL, ba nang le lymphoma e otlang habeli ea MYC-BCL2 ba bile le liphello tse mpe ka ho fetisisa, ka OS e mahareng ea likhoeli tse 6.6 feela, e tlase haholo ho feta mefuta e meng ea HGBL (HGBL-DH MYC-BCL6: likhoeli tse 13.6, HGBL-NOS: likhoeli tse 18.5) le bakuli bao e seng ba HGBL (likhoeli tse 11.8). Ho sa tsotellehe sena, ha ho na phapang e kholo ho OS kapa PFS e fumanoeng ha ho bapisoa nako ea infusion ea CAR-T.
Polokeho ea phekolo ea CAR-T e ne e tsitsitse ho pholletsa le lihlopha tsa HGBL le tse seng tsa HGBL. Ho hlaha ha cytokine release syndrome (CRS) le immune effector cell-associated neurotoxicity syndrome (ICANS) ho ne ho tšoana lipakeng tsa lihlopha tsena tse peli. Leha ho le joalo, 38% ea bakuli ba HGBL ba ne ba hloka tlhokomelo ea ICU bakeng sa CRS, leha sena se ne se bapisoa le litlhoko tsa kalafo tse bonoang ho bakuli bao e seng ba HGBL.
Phuputso ea DESCAR-T LYSA e totobatsa bokhoni ba phekolo ea CAR-T ho ntlafatseng tebello ea bakuli ba nang le HGBL, esita le meleng ea kalafo ea morao. Leha CAR-T e kanna ea se hlōle ka botlalo tebello e mpe ea lefu lena e amanang le mefuta e meng e kotsi haholo, joalo ka HGBL e imetsoeng habeli, thuto ena e khothalletsa ho kenella kapele ka phekolo ea CAR-T, e ka fanang ka liphetho tse betere tsa ho phela. Ho feta moo, ho fokotsa nako pakeng tsa leukapheresis le ho kenngoa ha CAR-T ho ka ba bohlokoa bakeng sa bakuli ba nang le lefu le matla joalo ka HGBL.
Phuputso ena e totobatsa bohlokoa ba phekolo ea CAR-T e le phekolo e sebetsang bakeng sa lymphoma ea B-cell ea boemo bo holimo 'me e fana ka temohisiso ea bohlokoa mabapi le ho ntlafatsa linako tsa kalafo bakeng sa liphetho tse betere tsa mokuli. Lithuto tse ling lia hlokahala ho hlahloba litsela tsa ho ntlafatsa katleho ea phekolo ea CAR-T, haholo-holo mefuteng e thata ea lymphoma.