1 / 94

Lymphomes diffus à grandes cellules B Facteurs pronostiques et traitement

Lymphomes diffus à grandes cellules B Facteurs pronostiques et traitement. André Bosly, M.D., Ph.D. Université de Louvain Mont-Godinne, Belgique ESH Tunis, le 29 octobre 2010. Lymphomes diffus à grandes cellules B Facteurs pronostiques et traitement. Données épidémiologiques.

carnig
Download Presentation

Lymphomes diffus à grandes cellules B Facteurs pronostiques et traitement

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement André Bosly, M.D., Ph.D. Université de Louvain Mont-Godinne, Belgique ESH Tunis, le 29 octobre 2010

  2. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement Données épidémiologiques

  3. Mortalité par cancer par an (nx 1000) en Europe

  4. Age-standardized incidence rates (ASR) of NHL worldwide Müllier A et al, Ann Hematol 2005; 84 : 1-12

  5. SEER 1975–2000 age-adjusted incidence rates of NHL by gender Fischer SG et al, Oncogene 2004; 23:6524-6534

  6. Frequency of subtypes of lymphomas Non-Hodgkin's lymphomas. Coiffier, p. 7

  7. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement Facteurs pronostiques cliniques : l’IPI

  8. International prognostic index Smith A. Br J Haematol 2010; 148:739-753

  9. Survival according to IPI score 6696 patients included in GELA randomized studies Overall survival Progression-free survival

  10. Revised IPI in the rituximab era Sehn LH et al, Blood 2007; 109:1857–1861

  11. RIPI 4-year PFS 4-year OS Sehn et al, Blood 2007; 109 : 1857-61

  12. Comparaison de 4 IPI Advani RH et al, BHJ 2010; 151 : 143-151

  13. Validity of IPI in the rituximab era (german group) Ziepert M., J Clin Oncol 2010; 28:2373-2380

  14. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement Facteurs biologiques : données de micro-array : au moins deux maladies

  15. Gene expression arrays Subclassification of diffuse large B-cell lymphoma Alizadeh et al, Nature 2000

  16. Clinical study according to phenotype of diffuse large cells lymphomas (Alizadeh, 2000)

  17. Subgroups of diffuse large B-cell lymphoma defined by gene expression profiling 274 DLBCL Biopsy Samples

  18. Diffuse Large B-cell Lymphoma : at least two diseases Germinal center B cell-like (GCB) Activated B cell-like (ABC) Germinal center B cell ? Post-Germinal Center B cell Cell of Origin - t(14;18) translocation of BCL-2 - Chr. 2p amplification of c-rel locus Constitutive activation of NF-kB Oncogenic Mechanisms Favorable 60% 5-yr survival Poor 35% 5-yr survival Clinical Outcome

  19. GCB and ABC in R-CHOP treated patients Lenz et al, NEJM 2008; 359 (22) : 2313-23

  20. Hartmann & Rosenwald, EHA educational program 2009

  21. Predictor score in R-CHOP treated patients N Engl J MED. G. Lenz et al. 2008; 359 (22): 2313-23

  22. Stromal 1 N Engl J MED. G. Lenz et al. 2008; 359 (22): 2313-23

  23. Stromal 2 N Engl J MED. G. Lenz et al. 2008; 359 (22): 2313-23

  24. Survival model in R-CHOP treated patients N Engl J MED. G. Lenz et al. 2008; Suppl. to 359 (22): 2313-23

  25. Survival model and IPI N Engl J MED. G. Lenz et al. 2008; Suppl. to 359 (22): 2313-23

  26. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement Facteurs biologiques : expression de gènes en immunohistologie

  27. Ricover study : Hans algorithm Ott G et al, Blood 2010-03-276766

  28. RICOVER study : Hans algorithm All patients : Ott G et al, Blood 2010-03-276766

  29. EFS, R-CHOP patients (52 patients)

  30. Ott et al, Blood 2010

  31. RICOVER study histology Ott G et al, Blood 2010-03-276766

  32. RICOVER study histology Ott G et al, Blood 2010-03-276766

  33. Hans algorithm Muris algorithm Nyman algorithm Nyman H et al, Modern Pathology 2009; 22 : 1094-1101

  34. Nyman Muris Hans Nyman H et al, Modern Pathology 2009; 22 : 1094-1101

  35. Lunenburg consortium CV1=2; CV2=1 CV1=26; CV2=4 CV1=20; CV2=11 CV1=15; CV2=16 de Jong D et al, J Clin Pathol 2009; 62 : 128-138

  36. Lunenburg consortium CV1=31; CV2=21 CV1=23; CV2=20 CV1=21; CV2=11 CV1=27; CV2=21 de Jong D et al, J Clin Pathol 2009; 62 : 128-138

  37. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement Réarrangements de MYC et survie

  38. Smith SM et al, Blood Cells Mol Diseases 2010

  39. Réarrangement de c-myc et DLBCL Univariate Kaplan-Meier analysis of overall survival in the MYC rearrangement (MYC-R) versus nonrearranged patients. Patients with rearrangement of MYC have a significantly inferior outcome compared to those without (hazard ratio, 2.03; 95 % CI, 1.15 to 3.58). The probability of survival at 2 years was 0.35 in the MYC rearrangement group versus 0.61 for all others, based on n=240 patients with MYC data and clinical follow-up. Barrans S et al., J Clin Oncol 2010; 28:3360-3365

  40. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement Dose-intensité de chimiothérapie et survie

  41. Effect of dose-intensity on survival Bosly, Bron et al, Ann Hematol 2008

  42. Lymphomes diffus à grandes cellules BFacteurs pronostiques et traitement TEP et évaluation de la réponse précoce

  43. PET CT for staging TP 15112007

  44. Early treatment evaluation

  45. Early treatment evaluation Before treatment At 2 cycles At 4 cycles FDG-PET2 (+)

  46. Event-free survival and overall survival according to response at 2 cycles on the basis of PET (n = 90) Event-free survival Overall survival 100 80 60 40 20 0 100 80 60 40 20 0 PET– (n=54) Probability of OS Probability of EFS Median follow-up: 2 years PET+ (n=36) p=0.006 p<0.0001 0 1 2 3 0 1 2 3 Years after randomisation Years after randomisation Haioun C, et al, Blood 2005

  47. Specificity and sensitivity of PET are not so good in DLBCL in comparison with HD Receiver operating characteristic (ROC) plotting for (A) advanced-stage Hodgkin's lymphoma and (B) diffuse large B-cell lymphoma. Individual study estimates of sensitivity and 1 − specificity are shown (open circles). Summary ROC curve is presented only for DLBCL. Closed square represents the summary estimates. Dashed boundary represents the 95% confidence region for the summary sensitivity and specificity. Terasawa T et al, J Clin Oncol 2009; 27 : 1906-1914

  48. Interim PET NHL (4 cycles) False positive PET scans – PPV 26% SUV = 1.4 False positive PET results Visual assessment : normal Interval : 10 – 14 days G-CSF Moskowitz et al, J Clin Oncol 28: 1896, 2010

  49. Interim PET in ABVD-treated HL patients SUV = 3.5 Gallamini, A. et al. J Clin Oncol; 25:3746-3752 2007

  50. Visual vs. quantitative analysis 2 cycles, n=92 Visual analysis (Créteil, MRU) Quantitative analysis (SUVmax at 2 cycles) Quantitative analysis (% reduction SUVmax) > 65.7%  5.0 PET2 (-) Probability of EFS P < .0001 PET2 (+) P = .002 > 5.0 P =.009  65.7% Months after inclusion Months after inclusion Months after inclusion  Reduction of 14/17 false positives  Cut-off may vary with histology, treatment, PET center Lin, Itti et al. J Nucl Med 2007;48:1626-32

More Related