Diagnostika a liečba relabovaného a refraktérneho DLBCL

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1 Diagnostika a liečba relabovaného a refraktérneho DLBCL Miriam Ladická Národný onkologický ústav

2

3 Vysoká účinnosť Akceptovateľná Liečba ochorenia toxicita Minimálne neskoré NÚ cca 1/3 pacientov s DLBCL 7% neskorých relapsov (po >5 rokoch) Pacient Zber PKB/KD Darca Transplantačný režim Myeloablat/RIC Transplantácia Auto/Alo PKB/KD Udržiavacia liečba Imunosupresia/DLI Friedberg JW. Relapsed/refractory Diffuse Large B-Cell Lymphoma. Hematology 2011

4 CORAL protokol (Collaborative Trial in Relapsed Aggressive Lymphoma) Gisselbrecht C et al. JCO 2010;28:

5 CORAL - výsledky Lymfómová skupina Slovenska relaps <12m od diagnózy relaps >12m od diagnózy Gisselbrecht C et al. JCO 2010;28:

6 CORAL - výsledky Gisselbrecht C et al. JCO 2012;30:

7 CORAL - výsledky Lymfómová skupina Slovenska R-DHAP R-ICE R-DHAP R-ICE Thieblemont C et al. JCO 2011;29:

8 R-DHAP verzus R-GDP

9 R-DHAP verzus R-GDP - efektivita

10 R-DHAP verzus R-GDP - toxicita

11 Liečba ochorenia Cca 2/3 pacientov s chemosenzítívnym DLBCL Pacient Zber PKB/KD Darca Vysoká účinnosť Transplantačný režim Akceptovateľná toxicita Myeloablat/RIC Minimálne neskoré NÚ Transplantácia Autológna Auto/Alo transplantácia PKB/KD Mortalita ASCT < 5% Udržiavacia liečba Imunosupresia/DLI

12 R-BEAM verzus I131Tositumomab-BEAM Vose J M et al. JCO 2013;31:

13 Liečba ochorenia Pacient Zber PKB/KD Darca Transplantačný režim Myeloablat/RIC Transplantácia Auto/Alo PKB/KD Udržiavacia liečba Imunosupresia/DLI

14 CORAL výsledky udržiavacej liečby Podľa pohlavia Udržiavacia liečba rituximabom Bez udržiavacej liečby rituximabom Gisselbrecht C et al. JCO 2012;30:

15 Protilátková liečba pri DLBCL Protilátka Cieľ Odpovede (%) Rituximab CD20 30 Epratuzumab CD22 10 Rituximab+Epratuzumab CD20+CD22 47 CMC544 CD22 33 Rutuximab+CMC544 CD20+CD22 80

16 Nové lieky skúšané v liečbe DLBCL Liek Cieľ Molekulová skupina Bortezomib NF-kB ABC Fostamatinib Syk ABC Ibrutinib BTK ABC Cal 101 PI3K ABC Enzastaurin PKCb ABC Navitoclax BCL2 GCB (?) EZH2 inhibítor EZH2 GCB Bevacizumab VEGF Stromal-2 Lenalidomid Angionegéza, NF-kB Stromal-2, ABC Sehn, LH. Paramount prognostic factors that guide therapeutic strategies in diffuse large B-cell lymphoma. Hematology 2012;

17 Liečba ochorenia Pacient Zber PKB/KD Darca Odpovede po ASCT CHT senzit 40-50% CHT rezist 10-20% EFS/PFS po ASCT podľa rizikových faktorov 15-60% Transplantačný režim Myeloablat/RIC Transplantácia Auto/Alo PKB/KD Postavenie alogénnej transplantácie Mortalita Alo Tx MAC 28-56% RIC/NMAC 23-47% Udržiavacia liečba Imunosupresia/DLI E.Klyuchnikov, et al. BMT 2014; 49: 1-7, Gisselbrecht C et al. JCO 2010;28: , Thieblemont C et al. JCO 2011;29:

18 Auto verzus alo transplantácia ako prvá Tx pri chemosenzitívnom relapse DLBCL Refract/resist (%) Robinson ASH 2012

19 Alo verzus auto - trasplantácia kmeňovými krvotvornými bunkami Alogénna transplantácia KKB Výhody Efekt graft verzus tumor (GVT) Nekontaminované KKB Nevýhody Vyššia toxicita (režim, imunosupresia, graft verzus host disease) Limitovaná dostupnosť darcov Vyššia cena Autológna transplantácia KKB Výhody Nižšia toxicita Nižšia cena Nevýhody Chýba GVT efekt Kontaminácia KKB? Zlyhanie zberu KKB (ťažko preliečení pacienti) Riziko vzniku MDS

20 Postup pri liečbe Lymfómová skupina Slovenska relapsu/refraktérneho DLBCL Podľa E.Klyuchnikov, et al. BMT 2014; 49: 1-7

21 Problém - histologizácia! Prečo ju robiť? Vylúčenie:- iných typov lymfómov - inej nehematologickej malignity - infekcie Prítomnosť CD 20 pozitivity Kedy ju robiť? Relaps po viac ako 12 mesiacoch od stanovenia diagnózy a po dosiahnutí KR Nejednoznačný CT resp. PET nález: - lokalizovaná pozitivita (potvrdenie KR) - diferencová odpoveď na liečbu Armitage AO. My treatment approach to patients with diffuse large B cell lymphoma. Mayo Clin Proc. 2012;87(2): Tilly H et al. Difuse large B- cell lymphoma: ESMO Clinical praktice guidelines for diagnosis, treatment and follow-up. Ann od Oncol 23(supp 7) 2012

22 Ďakujem za pozornosť Lymfómová skupina Slovenska

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