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Peripheral T Cell Lymphoma Prognostic Factors

Peripheral T Cell Lymphoma Prognostic Factors. Dennis D. Weisenburger, M.D. for the International PTCL Study. Prognostic Factors. Histologic type – ALCL,ALK+ good International Prognostic Index (IPI) Clinical features – B symptoms, β 2-microglobulin, bulky disease, etc;

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Peripheral T Cell Lymphoma Prognostic Factors

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  1. Peripheral T Cell LymphomaPrognostic Factors Dennis D. Weisenburger, M.D. for the International PTCL Study

  2. Prognostic Factors • Histologic type – ALCL,ALK+ good • International Prognostic Index (IPI) • Clinical features – B symptoms, β2-microglobulin, bulky disease, etc; • Pathologic features – transformed cells, proliferation, EBV infection, etc;

  3. International PTCL Study Purpose To assess the clinical applicability and reproducibility of the new WHO classification of peripheral T-cell and NK-cell lymphomas

  4. Case Selection • Previously-untreated adult patients (>19 yrs) with de novo peripheral T-cell or NK/T-cell lymphoma, • excluding mycosis fungoides and Sézary syndrome • Initial presentation between January 1, 1990, and December 31, 2002 • Consecutive cases representative of the geographic region • Tissue biopsies adequate for diagnosis and classification • Clinical features, treatment and follow-up information

  5. International PTCL Study

  6. International PTCL StudyContributing Sites • North America – Omaha, Vancouver, Bethesda, Boston, Los Angeles, Tucson • Europe – Barcelona, Madrid, London, Oslo, Lyon, Wuerzburg, Bologna • Far East – Seoul, Hong Kong, Singapore, Bangkok, Tokyo, Nagoya, Okayama, Fukuoka

  7. Overall Survival by diagnosis group 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time Diagnosis CENSOR FAIL TOTAL MEDIAN Adult T-cell leuk/lymph (ATLL) 23 103 126 0.79 Anaplastic large cell lymphoma, ALK- 38 33 71 4.49 Anaplastic large cell lymphoma, ALK+ 63 27 90 . Angioimmunoblastic T-cell lymphoma 87 154 241 2.26 Peripheral T-cell lymphoma 112 218 330 2.01 Generic NK-cell 49 85 134 0.65

  8. Overall Survival by diagnosis group 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 Time Diagnosis CENSOR FAIL TOTAL MEDIAN Enteropathy-type T-cell lymphoma 9 52 61 0.88 Hepatosplenic T-cell lymphoma 3 16 19 0.67 Subcutaneous panniculitis-like T-cell ly 7 5 12 6.19 Primary cutaneous ALCL 20 3 23 .

  9. Overall Survival Nasak NK/T and Nasal-type NK/T and Aggressive/Unclass. NK/T 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 Time Diagnosis CENSOR FAIL TOTAL MEDIAN Nasal NK/T-cell lymphoma 42 50 92 1.61 NK/T-cell lymphoma, nasal type 5 29 34 0.36 Unclassifiable or Aggressive NK-cell leu 2 6 8 0.23

  10. Survival in PTCL correlates with IPI Scores

  11. Survival in PTCL Correlates with IPI Scores

  12. Consensus Diagnoses

  13. Overall Survival Disease Category: Peripheral T-cell lymphoma by IPI 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time IPI CENSOR FAIL TOTAL MEDIAN 0/1 40 47 87 5.11 2 38 72 110 2.1 3 19 51 70 1.41 4/5 9 39 48 0.67

  14. Overall Survival Disease Category: Peripheral T-cell lymphoma by Marrow Involvement 1.0 0.9 Test: p=0.027 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time Bone marrow involvement CENSOR FAIL TOTAL MEDIAN no 87 159 246 2.11 yes 20 52 72 1.12

  15. Overall Survival Disease Category: Peripheral T-cell lymphoma by T-IPI 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time T-IPI CENSOR FAIL TOTAL MEDIAN 0 31 33 64 4.68 1 42 76 118 2.1 2 25 65 90 1.46 3/4 8 35 43 0.7

  16. Clinical Features of PTCL-NOS

  17. Overall Survival Disease Category: Peripheral T-cell Lymphoma-NOS by Transformed T-cell counts 1.0 0.9 Test: p=0.0078 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time Median transformed T-cell count CENSOR FAIL TOTAL MEDIAN <=30% 37 49 86 3.23 31-70% 33 56 89 2.03 >70% 19 60 79 1.23

  18. Overall Survival Disease Category: Peripheral T-cell Lymphoma-NOS by Ki67+ cells 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time Ki67+ cells (%) CENSOR FAIL TOTAL MEDIAN <=25% 25 27 52 5.26 26-75% 35 68 103 1.89 >75% 12 44 56 1.36

  19. Overall Survival PTCL-US vs. PTCL-LE 1.0 0.9 Test: p=0.0032 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Time Diagnosis CENSOR FAIL TOTAL MEDIAN PTCL, unspecified 88 204 292 1.83 PTCL, lymphoepithelioid variant 18 10 28 17.2

  20. Clinical Features of PTCL-US and PTCL-LE

  21. Final Multivariate Analysis of PrognosticFactors in PTCL-NOS

  22. Overall Survival Peripheral T-cell Lymphoma-NOS, and Disease sub-group: Angioimmunoblastic T-cell lymphoma 1.0 0.9 Test: p=0.89 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time Diagnosis CENSOR FAIL TOTAL MEDIAN Angioimmunoblastic T-cell lymphoma 87 154 241 2.26 Peripheral T-cell lymphoma-NOS 112 218 330 2.01

  23. Clinical Prognostic Factors of PTCL-NOSvs. Angioimmunoblastic (AI)

  24. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by IPI 1.0 0.9 Test: p=0.096 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Time IPI CENSOR FAIL TOTAL MEDIAN 0/1 15 15 30 5.94 2 23 39 62 2.93 3 22 45 67 1.67 4/5 18 44 62 1.37

  25. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by patient age 1.0 0.9 Test: p=0.036 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time Age CENSOR FAIL TOTAL MEDIAN <=60 40 60 100 3.21 >60 47 94 141 1.68

  26. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by performance status 1.0 0.9 Test: p=0.0022 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time Performance status CENSOR FAIL TOTAL MEDIAN Ambulatory 63 85 148 3.1 Non-ambul. 22 67 89 1.37

  27. Overall Survival Disease Sub-group: Angioimmunoblastic T-cell lymphoma by B-symptoms 1.0 0.9 Test: p=0.0046 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time B symptoms CENSOR FAIL TOTAL MEDIAN no 36 38 74 4.8 yes 51 116 167 1.62

  28. Overall Survival Disease Sub-group: Angioimmunoblastic T-cell lymphoma by Platelet Count 1.0 0.9 Test: p=0.017 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Time Platelet Count CENSOR FAIL TOTAL MEDIAN <150K/cmm 19 41 60 1.03 >=150K/cmm 52 90 142 2.4

  29. Overall Survival Disease Category: Angioimmunoblastic by Transformed T-cell counts 1.0 0.9 Test: p=0.14 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Time Median transformed T-cell count CENSOR FAIL TOTAL MEDIAN <=30% 47 72 119 2.4 31-70% 25 51 76 1.52 >70% 5 13 18 1.76

  30. Overall Survival Disease Category: Angioimmunoblastic T-cell Lymphoma by UNMC-IPI2 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Time UNMC-PI2: Age / Perf. Stat / Plt Ct<150k CENSOR FAIL TOTAL MEDIAN 0 8 7 15 6.03 1 20 32 52 4.26 2 33 45 78 1.68 3 9 37 46 1.37 4 1 9 10 0.51

  31. Overall Survival Disease Sub-group: Anaplastic large cell lymphoma, ALK+ by IPI 1.0 0.9 0.8 Test: p<0.001 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time IPI CENSOR FAIL TOTAL MEDIAN 0/1 31 4 35 . 2 12 6 18 . 3 4 7 11 0.6 4/5 4 6 10 1.73

  32. Overall Survival Disease Sub-group: Anaplastic large cell lymphoma, ALK+ by Hemoglobin 1.0 0.9 Test: p=0.043 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time Hemoglobin CENSOR FAIL TOTAL MEDIAN <11 g/dl 8 6 14 . >=11 g/dl 32 9 41 .

  33. Overall Survival Disease Sub-group: Anaplastic large cell lymphoma, ALK- by IPI 1.0 0.9 Test: p<0.001 0.8 0.7 0.6 Proportion 0.5 0.4 0.3 0.2 0.1 0.0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Time IPI CENSOR FAIL TOTAL MEDIAN 0/1 22 5 27 . 2 8 4 12 . 3 5 11 16 1.71 4/5 2 8 10 0.66

  34. Conclusions • Histologic type is a good predictor of survival • IPI is a good predictor of survival in PTCL-NOS along with % of transformed cells • IPI is a poor predictor of survival in angioimmunoblastic type and better prognostic models are needed • IPI is a good predictor of survival in ALCL,ALK+ (along with Hgb <11g/dl) and ALCL,ALK-

  35. Conclusions • IPI is useful for stratification of most PTCL patients for risk-adapted therapies • New clinical, pathological and molecular genetic predictors are needed to develop more biologically-relevant prognostic models for the various disease entities

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