MCO 2011 - Slide 6 - M. Ghielmini - Spotlight session - Haematological diseases (lymphoma and myeloma)
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MCO 2011 - Slide 6 - M. Ghielmini - Spotlight session - Haematological diseases (lymphoma and myeloma)
- 1. Update on lymphoma and myeloma 2011 Michele Ghielmini Oncology Institute of Southern Switzerland (IOSI) Swiss Group for Clinical Cancer Research (SAKK)
- 3. Is ABVD still the gold standard for advanced Hodgkin’s lymphoma?
- 4. ABVD superior to MOPP or MOPP-ABVD Failure-free Survival Overall Survival Cannellos, NEJM, 2002 Same efficacy, less toxicity
- 5. Randomised ABVD vs Stanford V vs MOPPEVCAD Gobbi et al, JCO, 2005 Overall Survival Freedom From Progression Irradiation of maximum 2 sites
- 7. Stanford V regimen vs COPP-ABVD Hoskin et al, JCO 2009
- 8. COPPEBVCAD vs BEACOPP vs ABVD Federico et al, JCO 2009
- 9. Standard or escalated BEACOPP vs COPP-ABVD Engert et al, JCO 2009 Arm A = COPP-ABVD Arm B = BEACOPP Standard Arm C = BEACOPP Escalated
- 10. Standard or escalated BEACOPP vs COPP-ABVD Engert et al, JCO 2009 Incidence of secondary AML/MDS Benfit by International Prognostic Score Arm A = COPP-ABVD Arm B = BEACOPP Standard Arm C = BEACOPP Escalated
- 11. Competing Causes of Mortality in HD Long-term side-effects of HL treatment
- 13. Should interim PET guide treatment in aggressive NHL (DLBCL)?
- 15. Retrospective: end of treatment PET
- 18. Progression Free Survival according to PET after C2 Pet-neg (n=70) Pet-pos (n=42) P <0.0001 Median Follow-up 38 months (months) 5-y PFS : PET-neg = 81% [CI95%:70%-92%] PET-pos = 47% [CI95%:32%-62%] ASH 2009, Safar et al
- 20. Post-therapy but not interim PET predicts outcome in DLBCL A. Cashen, et al . ASH 2008 abs.# 371
- 21. Italian study in DLBCL 18-months PFS Interim PET 18-months PFS Final PET ASH 2009, Abstract 99, Pregno et al PET positive 61% PET negative 84% PET positive 74% PET negative 84% p.198 p. 015
- 23. Watch and wait or R-CHOP in follicular lymphoma ?
- 24. FL remains an incurable disease, but new therapies improved survival Fisher et al, JCO, 2005 Liu et al, JCO, 2006 MD Anderson SWOG
- 25. Waiting does not increase the incidence of transformation Al Tourah et al., JCO, 2008 BC cancer agency, Vancouver
- 26. 3 randomised studies of W + W vs immediate chemotherapy Overall survival Ardeshna et al, The Lancet 2003 W+W vs ProMACE-MOPP 89 pts Young 1988 W+W vs Prednimustine 130 pts Brice 1997 W+W vs Chlorambucil 309 pts Ardeshna, 2003
- 28. Prolonged remission does not mean longer survival Peterson et al., JCO 2003 Relapse-free survival CTX CTX CHOP-B P = 0.009 Overall survival CHOP-B CTX P = 0.107
- 29. EFS according to response to rituximab induction treatment P<0.0001 P<0.0001 35% of responders still in remission at 8 years Ghielmini et al, ASCO 2009
- 30. W + W or single agent rituximab ? Proportion of patients with no new treatment initiated 19 192 19 84 83 187 Events Totals W+W R4 R4 + M 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Years from randomisation 0 1 2 3 4 5 % not requiring Rx at 3yr W+W=48% R4=80% R4+RM=91% Ardeshna et al, ASH 2010
- 31. PFS by subentities for R-bendamustine vs R-CHOP 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Follicular p = 0,0281 Mantle cell p = 0,0146 Marginal zone p = 0.6210 Waldenström B-R B-R B-R B-R CHOP-R CHOP-R CHOP-R CHOP-R p = 0.0024 ASH 2009, Abstract 405, Rummel et al 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0 12 24 36 48 60 72 0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 Follicular p = 0,0281 Mantle cell p = 0,0146 Marginal zone p = 0.6210 Waldenström B-R B-R B-R B-R CHOP-R CHOP-R CHOP-R CHOP-R p = 0.0024
- 33. Mantle Cell Lymphoma: should anybody be transplanted in first line?
- 35. Combination chemotherapy (series with n = 26-62) Ghielmini and Zucca, Blood 2009 Regimen RR (%) EFS (mos) 2yOS (%) CVP 60-84 10-20 45-65 CHOP 75-88 7-21 60-76 MCP 63-73 13-15 85 R-CHOP 94-96 17-20 76 R-MCP 71 18 - CR rates w/o R: 10-40% CR rates w R: 30-50%
- 37. European MCL Network Progression Free Survival N=122 Median PFS, 39 mos. (ASCT) vs . 17 mos (IFN) Dreyling et al. Blood 2005 4-6x CHOP-like induction 2x CHOP-like consolidation IFN- α maintenance Dexa-BEAM mobilization Cyclo-TBI ASCT PR, CR R E L A P S E
- 38. Analysis of 3 pooled trials: ASCT vs. IFN Overall survival Dreyling et al, ASCO 2009
- 39. The Nordic trial of PBSCT in MCL n = 160 Age < 66 MCL 2 R-maxi CHOP R-HD-AraC R-in-vivo purging BEAM MCL 1 maxi CHOP BEAM Geisler et al., Blood 2008
- 40. MCL Younger < 65 years Dexa BEAM Cyclo TBI + Autograft P B S C harvest Ara-C, Melphalan TBI + Autograft 3-monthly follow-up 1 9 5 13 17 week R-CHOP/R-DHAP alternating 3-weekly 1 9 5 13 17 week R-CHOP 3-weekly 3-monthly follow-up P B S C harvest MRD MRD 2-3 monthly intervals MCL younger < 65 yrs. MCL European Network Study Hermine et al., ASH 2010 R
- 41. Time to treatment failure p=0.0382 (one sided sequential test) Hazard Ratio 0.68 Hermine et al., ASH 2010
- 43. CLL: is there a standard first line treatment?
- 46. New prognostic factors Döhner, NEJM, 2000 Orchard, Lancet, 2004 Cytogenetics Ig VH status
- 47. Alkylators or fludarabine in advanced CLL (Binet B or C) (randomised studies) OS Rai et al, NEJM, 2000 Leporrier et al, Blood, 2001 OS
- 48. Fludarabine +/- Rituximab in advanced CLL (retrospective, historical comparison) Byrd et al, Blood, 2005
- 49. R-FC vs. FC in CLL The Lancet 2010; 376:1164-74
- 50. Transplantation for CLL with unmutated VH gene No randomised, large study available ! Dreger, Blood, 2004 Moreno, JCO, 2005 Autologous (OS, 29 + 29 matched controls) Allogeneic (n=14 allo, 20 auto, historical)
- 53. What is the role of new drugs in the treatment of multiple myeloma?
- 54. Evolution of myeloma mortality Survival Months Kumar SK, Blood 2008
- 55. MM: Autologous transplant improves survival Attal, NEJM, 1996 Child, NEJM, 2003 Overall 1 year of life gained Meta-analysis of 3 trials
- 57. Induction regimens for MM Stewart et al, Blood, 2009 Caution : small single centre experiences no evidence that response = survival
- 58. VEL-DEX vs VAD Harousseau et al, ASH, 2009 Study IFM 2005 – 01 Vel/Dex (n=79) VAD (n=82) CR + VGPR CR/VGPR post PBSCT 43% 68% 26% 47% P< 0.05 Side effects Mucositis G3/4 Neuropathy AE causing off-study 1% 27% 2% 10% 7% 4%
- 59. Vel/Thal/Dex vs Thal/Dex Cavo et al, ASH, 2009 Randomised trial The addition of Bortezomib seems to abolish the negative prognostic effect of unfavorable cytogenetics (del13, del 17, t(4;14)) VTD (n=92) TD (n=95) > PR > VGPR pre-PBSCT > VGPR post-PBSCT 93% 61% 88% 74% 28% 72%
- 62. Curability of Myeloma MD Anderson Cancer Center 829 pts 1987-2008 54% received HDT CR Dex 16% Thal 29% Vel/Len 42% predicitve factors for prolonged CR: younger age early HDT CR > 10 years: 2% Delasalle ASH 2009,
- 63. 1 1 -ICML 1 1 th INTERNATIONAL CONFERENCE ON MALIGNANT LYMPHOMA Palazzo dei Congressi, Lugano, Switzerland June 15 - 18 , 20 11 ORGANIZING COMMITTEE: M. Ghielmini (Bellinzona), Chair R.D. Gascoyne (Vancouver) J.O. Armitage (Omaha) M.K. Gospodarowicz (Toronto) F.E. Cotter (London) P.W.M. Johnson (Southampton) M.F. Fey (Bern) E. Zucca (Bellinzona) F. Cavalli (Bellinzona), President
Hinweis der Redaktion
- Pts with advanced HL (stage IIAX-IV) were randomised between ABVD and one of two prespecified multidrug regimens (MDRs): Alternating ChlVPP/PABlOE or Hybrid ChlVPP/EVA Six cycles were planned, plus two extra for slow responses. Involved field RT was recommended for incomplete response or bulk disease at presentation Pts with advanced HL (stage IIAX-IV) were randomised between ABVD and one of two prespecified multidrug regimens (MDRs): Alternating ChlVPP/PABlOE or Hybrid ChlVPP/EVA Six cycles were planned, plus two extra for slow responses. Involved field RT was recommended for incomplete response or bulk disease at presentation
- 50 untreated DLBCL Stage III (n=15) or IV (n=35) received standard R-CHOP21 x 6 Patients had FDG-PET/CT scans performed after cycle 2 (or 3) and at the completion of therapy. Two medical oncologists reviewed the FDG-PET/CT reports and interpreted them as positive, negative, or equivocal. A nuclear medicine radiologist then reviewed the scans and applied the consensus response criteria to score each case as positive or negative.
- 2 2 We kno from basic studies in the early 80´s, that 2-CdA is inducing apoptosos in dividing but also in resting cells independent from cell cycle. This observation lead to the idea, that this could be an advantage in the therapy of indolent lymphomas. It is well known that 2-CdA is very effective in the treatment of HCL, inducing very long lasting complete remissions. But 2-Cda has also been demonstrated to be effective in other indolent lymphoproliferative disorders like low-grade NHL, CLL and cutaneous lymphomas and also in relapsed ALL. It was in 1992, that the Group from the Scripps-Clinic in San Diego, and in 1995 also Liliemark and Juliusson demonstrated the efficacy of cladribine in pretreated patients with NHL. However, in these heavily pretreated patients a high rate of severe infectious problems was reported in the range of about 20-40%, probably due to the extensive pretreatment. In 1995, again Saven and Piro from the Scripps Clinic, demonstrated the activity of Cladribine for the first time in untreated indolent NHL. They used the 7-day continous infusion regimen with 0,1 mg/kg/d, which is the approved schedule in the USA using 2-CdA.
- Progression-free survival in all patients (A) and in patients with Binet stage B and C chronic lymphocytic leukaemia (B) Chemoimmunotherapy=fludarabine, cyclophosphamide, and rituximab. Chemotherapy=fludarabine and cyclophosphamide.