Chithandizo cha CAR-T Chathetsa Kunenedweratu Koyipa mu Lymphoma Yapamwamba ya B-Cell
Kafukufuku waposachedwapa wofalitsidwa mu Kupita Patsogolo kwa Magaziakuwonetsa kuti chithandizo cha maselo a CAR-T chimapereka zabwino zambiri zachipatala kwa odwala omwe ali ndi digiri yapamwamba. B-Cell Lymphoma (HGBL), mtundu woopsa kwambiri wa lymphoma yayikulu ya B-cell (LBCL). Kafukufuku wa DESCAR-T LYSA, wochitidwa ndi ofufuza aku France, adayang'ana kwambiri odwala omwe adalandira chithandizo cha CAR-T ngati chithandizo chachitatu kapena kupitirira apo, kuphatikiza omwe ali ndi MYC ndi BCL2 ndi/kapena BCL6 rearrangements—yomwe imadziwika kuti lymphoma ya “double-hit” kapena “triple-hit”.
Kafukufukuyu adalembetsa odwala 228 ochokera ku registry ya DESCAR-T yaku France, omwe 73 mwa iwo adapezeka ndi HGBL, pomwe ena 155 anali ndi LBCL yopanda HGBL. Cholinga cha kafukufukuyu chinali kuwunika chitetezo ndi magwiridwe antchito a chithandizo cha CAR-T m'magulu awa, ndi nthawi yowunikira yapakati ya miyezi 18.5.
Zomwe zapezeka zasonyeza kuti kuchuluka kwa mayankho onse (ORR) ndi kuchuluka kwa mayankho onse (CR) kunali kofanana pakati pa odwala a HGBL ndi omwe si a HGBL, pa 68% ndi 60% a HGBL, ndi 76% ndi 59% a omwe si a HGBL, motsatana (p=0.293 ndi p=0.923). Kuphatikiza apo, kupulumuka kwapakati kopanda kupita patsogolo (PFS) kwa odwala a HGBL kunali miyezi 3.2, poyerekeza ndi miyezi 4.5 kwa odwala omwe si a HGBL, ngakhale kusiyana kumeneku sikunali kofunikira kwambiri pa ziwerengero (p=0.103). Mofananamo, kupulumuka kwapakati (OS) kunali miyezi 15.4 kwa odwala a HGBL poyerekeza ndi miyezi 18.3 kwa odwala omwe si a HGBL (p=0.214).
Chochititsa chidwi n'chakuti, pamene OS inawerengedwa kuyambira tsiku limene odwala anayenerera kulandira chithandizo cha CAR-T, OS yapakati ya odwala a HGBL inatsika kufika pa miyezi 7.6, poyerekeza ndi miyezi 11.8 ya odwala omwe si a HGBL (p=0.062), zomwe zikusonyeza kuti nthawi yoperekera CAR-T imagwira ntchito yofunika kwambiri pakukweza zotsatira.
Pakati pa mitundu yosiyanasiyana ya HGBL, omwe ali ndi MYC-BCL2 double-hit lymphoma anali ndi zotsatira zoyipa kwambiri, pomwe OS yapakati inali miyezi 6.6 yokha, yotsika kwambiri kuposa mitundu ina ya HGBL (HGBL-DH MYC-BCL6: miyezi 13.6, HGBL-NOS: miyezi 18.5) ndi odwala omwe si a HGBL (miyezi 11.8). Ngakhale izi, palibe kusiyana kwakukulu pakati pa OS kapena PFS komwe kunapezeka poyerekeza nthawi yolowetsedwa kwa CAR-T.
Chitetezo cha chithandizo cha CAR-T chinali chofanana m'magulu onse a HGBL ndi omwe si a HGBL. Kupezeka kwa cytokine release syndrome (CRS) ndi immuno effector cell-associated neurotoxicity syndrome (ICANS) kunali kofanana pakati pa magulu awiriwa. Komabe, 38% ya odwala a HGBL amafunikira chisamaliro cha ICU cha CRS, ngakhale izi zinali zofanana ndi zomwe zimafunika pa chithandizo chomwe chimapezeka mwa odwala omwe si a HGBL.
Kafukufuku wa DESCAR-T LYSA akuwonetsa kuthekera kwa chithandizo cha CAR-T pakukweza chiyembekezo cha odwala omwe ali ndi HGBL, ngakhale atalandira chithandizo chamtsogolo. Ngakhale kuti CAR-T singathetseretu chiyembekezo choipa chokhudzana ndi mitundu ina ya matenda oopsa, monga HGBL yomwe yagwidwa kawiri, kafukufukuyu amalimbikitsa kuchitapo kanthu mwachangu ndi chithandizo cha CAR-T, chomwe chingapereke zotsatira zabwino zopulumuka. Kuphatikiza apo, kuchepetsa nthawi pakati pa leukapheresis ndi kulowetsedwa kwa CAR-T kungakhale kofunikira kwa odwala omwe ali ndi matenda oopsa monga HGBL.
Kafukufukuyu akugogomezera kufunika kwa chithandizo cha CAR-T ngati chithandizo chothandiza cha lymphoma yapamwamba ya B-cell ndipo amapereka chidziwitso chofunikira pakukonza nthawi yochizira kuti odwala apeze zotsatira zabwino. Maphunziro ena akufunika kuti afufuze njira zowonjezera mphamvu ya chithandizo cha CAR-T, makamaka m'magulu ang'onoang'ono ovuta a lymphoma.