TCH em Linfomas T. Fábio R. Kerbauy

Transcription

1 TCH em Linfomas T Fábio R. Kerbauy

2 T-Cell Lymphomas ( 6000 cases/y USA) J Clin Oncol 2008;26:

3 Proportion T-cell lymphomas prognosis by subtipe ALCL ALK ATLL AITL PTCL ALCL ALK- NK/T-nasal type EATCL Time. Vose J, et al. J Clin Oncol. 2008;26:

4 Proportion Remaining Alive OS by IPI score (CHOP) CR: 64% 5-Yr PFS: 29% 0.6 0,1 n = ,3 n = 54 4,5 n = Yrs. Savage KJ, et al. Ann Oncol. 2004;15:

5 Extra nodal T/NK Suzuki R, Curr Hematol Malig Rep Epub Ahead of Print

6 Outcome (1992 to 2009) Savage KJ, et al. Ann Oncol. 2004;15:

7 EFS CHOP x CHOEP (Including ALCL Alk+) German High-Grade Non-Hodgkin Lymphoma Study Group (n=343) - Age<60y Schmitz N, et al. Blood. 2010;116:

8 Relapsed T-Cell Lymphomas (no HCT) J BC- Mak V et al.clin Oncol 2013;31:

9 Impact of HCT- Problems Absence of randomized studies Heterogeneous group of patients Small number of patients Few options for cytoreduction before HCT Poor survival in patients with active disease at HCT High relapse rate High TRM

10 First-line chemotherapy and Auto HCT Trial Regimen N OS Rate PFS Rate GEL-TAMO* [1] HDT/ASCT yrs 5 yrs GEL-TAMO [2] MEGA-CHOP, then ASCT or IFE-ASCT 26 3 yrs 3 yrs Nordic Group [3] CHOEP-ASCT yrs Italian Group [4] HDT/ASCT yrs 12 yrs EBMT* [5] HDT/ASCT yrs 4 yrs Reimer et al [6] CHOP-ASCT 83 3 yrs 3 yrs Sieniawski et al [7] IVE/MTX-ASCT 57 3 yrs 3 yrs 40-70% Tx rate Rodriguez J, et al. Ann Oncol. 2003;14: Rodriguez J, et al. Eur J Haematol. 2007;79: D Amore F, et al. Ann Oncol. 2005;16(suppl 5):v56. Kyriakou C, et al. J Clin Oncol. 2008;26: Kyriakou C, et al. J Clin Oncol. 2008;27: Reimer P, et al. J Clin Oncol. 2008;27: Sieniawski M, et al. ASH Abstract 1660.

11 Front-line auto HCT Stanford 2008 Disease status before transplant Chen AI et al. BBMT. 2008; 14:

12 Up-front HDT/ASCT in PTCL: Phase II D Amore F, et al. J Clin Oncol. 2012;30:

13 Up-front HDT/ASCT in PTCL: Phase II PFS in 44% of treatment-naive patients with PTCL Therefore, dose-dense induction and HDT/ASCT are a rational up-front strategy in transplantationeligible patients with PTCL D Amore F, et al. J Clin Oncol. 2012;30:

14 Up-front HDT/ASCT in PTCL: Germany CHOP >> DexaBEAM >> TBI1200/Cy ou BEAM Whilhelm M, et al. Blood Cancer J. 2016;6: e452

15 Up-front HDT/ASCT in PTCL: Germany Whilhelm M, et al. Blood Cancer J. 2016;6: e452

16 The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma:lysa retrospective analysis J Fossard G et al Annals of Oncol 2018 Epub ahead of printing

17 J Fossard G et al Annals of Oncol 2018 Epub ahead of printing The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma:lysa retrospective analysis Overall, and in consideration of the study limitations, the data presented in this study do not 162x256mm (150 x 150 DPI) support the use of ASCT as a consolidation strategy for all responding patients with PTCLNOS, AITL or ALK- ALCL in first line. Further study is needed to precisely evaluate if a specific subgroup like patients with PET-defined PR, specific histologic or molecular subtype, might benefit from the procedure. Moreover, given the flaws of any retrospective data collection, the economic burden associated to ASCT in PTCL[27] and the absence of any consensus over the procedure, a large collaborative randomized trial should be undertaken to allow for a definitive answer.

18 The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience J Rohlfing S et al Annals of Hematol Epub ahead of printing

19 J Rohlfing S et al Annals of Hematol Epub ahead of printing The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience *Younger patients: Benefit OS (not EFS)

20 J Rohlfing S et al Annals of Hematol Epub ahead of printing The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience Relapsed/refractary patients

21 Up-front HDT/ASCT in PTCL Moderately better PFS/OS than population-based series with CHO(e)P Often younger patients Frail patients less likely to go on a HDT study IPI not recommended to define eligebility Does not address the high rates of primary failures in PTCL Randomized study Better first line treatments specific subtypes/new agents Maintenance therapy

22 Relapsed T-Cell Lymphomas (no HCT) J BC- Mak V et al.clin Oncol 2013;31:

23 Relapses/Refractory T-cel Auto HCT Group N DFS/PFS % OS % Stanford Relapsed Santanford Refractory South Korea Relapsed South Korea Refractary GEL-TAMO BSBMT/ABMTRR Memorial City of Hope UK Sweden Rodriguez J, et al. Ann Oncol. 2003;14: Rodriguez J, et al. Eur J Haematol. 2007;79: D Amore F, et al. Ann Oncol. 2005;16(suppl 5):v56. Kyriakou C, et al. J Clin Oncol. 2008;26: Kyriakou C, et al. J Clin Oncol. 2008;27: Reimer P, et al. J Clin Oncol. 2008;27: Sieniawski M, et al. ASH Abstract 1660.

24 The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience Relapsed/refractary patients J Rohlfing S et al Annals of Hematol Epub ahead of printing

25 Milan - Corradini P, et al. J Clin Oncol. 2004;22: OS (%) PFS (%) Allo-SCT for R/R PTCL Phase II trial Relapsed/refractory PTCL/AITL/ALCL NMA (Flu/Cy) N = 17 (8 prev ASCT) Median age: 41 yrs (range: 23-60) Time from diagnosis: 5-8 mos to 5 yrs Median follow-up: 28 mos 100 PFS: 64% Nonrelapse mortality at 2 yrs: 6%, later updated to: 12% OS: 80% 2/4 patient responses to DLI Mos

26 Allo-SCT for Relapsed PTCL Retrospective yr OS: 57% 5-yr EFS: 53% AITL (n = 11) 80% PTCL (n = 27) 63% ALCL (n = 27) 55% Other (n = 12) 33% Le Gouill S, et al. J Clin Oncol. 2008;26:

27 Refractary/Relapsed T-Cell Lymphomas PTCL: 135 AITL: 105 No ALCL J Chihara D et al. Br J Haematol. 2017: 176;

28 erall, 75 patients (8%) were consolidated with bone marrow transplantation, ctory and 22 relapsed patients. After a median follow-up of 38 months (range, entation of refractory/relapse disease, 440 patients had died. The median as 5.8 months, and the rates of 3-yr overall survival were 21% and 28% for apsed patients, respectively (p<0.001). Patients receiving or not salvage bone tation had a 3-yr survival rates of 48% and 18%, respectively, (p<0.001). In a instituições gression analysis, refractory disease was associated with a higher risk of p=0.001), whereas late relapse (>12 months, HR 0.57, p=0.001) and salvage nsplantation (HR=0.36, p<0.001) were associated with a better OS. No und in OS with respect to histology. ately reflects outcomes for patients treated according to standards of care lts confirm that peripheral T-cell lymphomas patients had dismal outcome after ession. Patients with chemotherapy sensitive disease who relapsed > 12 efit from consolidative bone marrow transplantation. : clinicaltrials.gov identifier: NCT J Bellei M et al.haematol Epub ahead of printing

29 Refractary/Relapsed T-Cell Lymphomas J Bellei M et al.haematol Epub ahead of printing

30 Relapsed Survival by auto HCT x no-hct J Bellei M et al.haematol Epub ahead of printing

31 Conditioning regimen BEAM or BEAC CBV TBI based GemBuMel BuMel LACE Benda-EAM

32 Conditioning regimen NMA/RIC (80%) FluCy FluMel FluTBI BEAM Etc

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34 Kharfan-Dabaja MA et al. BBMT. 2017: 23;

35 Kharfan-Dabaja MA et al. BBMT. 2017: 23;

36 Agosto/2014: 44a, linfoma T cutâneo (micose fungoide, variante foliculotrópico) eritrodermia e massas cervicais, axilares e inguinais há 4 meses + MO 15% infiltração CHOEP x 2

37 GDP x 2: resposta cutânea mas refratariedade linfonodos Ciclo par de Hyper-CVAD: RP (adenomegalia + MO) TCTH - FluMelTBI400 / FK-MTX-ATG - Doador: MUD, 10/10, ABO compatível

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39 @fkerbauy