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Roman Hájek on behalf of Czech Myeloma Group March 27, 2011 Olsztyn

„ Treatment standards of myeloma in the Czech Republic ; Lenalidomide (Revlimid) in myeloma treatment and an assessment of its efficacy; Objectives and activity of the Czech Myeloma Group”. Roman Hájek on behalf of Czech Myeloma Group March 27, 2011 Olsztyn. PART I

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Roman Hájek on behalf of Czech Myeloma Group March 27, 2011 Olsztyn

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  1. „Treatment standards of myeloma in the Czech Republic; Lenalidomide (Revlimid) in myeloma treatment and an assessment of its efficacy; Objectives and activity of the Czech Myeloma Group”. Roman Hájek on behalfofCzechMyelomaGroup March 27, 2011 Olsztyn

  2. PART I „Treatment standards of myeloma in the Czech Republic“

  3. Wherewe are going ? Thereis evidence thatnewdrugs cansignificantlychangeprognosis

  4. Ourtreatmentstandardsforroutinelife in period 2010-2011 To use ofthalidomideandbortezomib (VELCADE) based regimentas first line treatment in allpatientsup front + autologoustransplantation in allavailablepatients

  5. Ourtreatmentstandardsforroutinelife in period 2010-2011 To use VELCADE/THALIDOMIDE/REVLIMIDEbased regimentas secondandthird line treatment in allpatients + autologoustransplantation in allavailablepatients

  6. 1. NEW DIAGNOSIS: THALIDOMID BORTEZOMIBbasedregimen + melphalan-prednison (MPT/MPV) or CDT/CVD1-3. FIRST RELAPSE: THALIDOMID VELCADE REVLIMIDEbasedregimenor MP

  7. STOP RULESReason for the Treatment Discontinuation If we have more than one treatment options than we have change treatment when it is: A: NOT EFFECTIVE B: POORLY TOLERATED CHECK POINT: after 4 cycles of therapy

  8. ReasonfortheTreatmentDiscontinuation (primotherapyandfirstrelapse) STABLE DISEASE IS NOT SUTISFIED RESPONSE MINIMAL RESPONSE (M-Ig < 50%) IS NOT SUTISFIED RESPONSE

  9. ReasonfortheTreatmentDiscontinuation (primotherapyandfirstrelapse) STABLE DISEASE IS NOT SUTISFIED RESPONSE MINIMAL RESPONSE (M-Ig < 50%) IS NOT SUTISFIED RESPONSE WE NEED AT LEAST PARTIAL RESPONSE

  10. Benefit of the new drugs - thalidomide and bortezomibe, lenalidomide New drugs have significant benefit for patients with relapse and resistant diseaseThe key rules are: 1. Do not use monotherapy2. Reserve other new drugs for the future

  11. CTD junior and senior JUNIOR SENIORCyclophosphamide 800mg i.v./p.o. day 1, 8, 15 50mg dailyThalidomid 200 mg 100 mgDexamethazon 40 mg day 1-4, 15-18 20 mg

  12. VELCADE 1x vs. 2x weeklyschedule ( to avoidpolyneuropathy) JUNIOR: day 1,4,8,15 - 28 days SENIOR: day 1,8,15 - 28 days CVD junior and senior VMP junior and seniorVD or VP junior and senior

  13. UNIVERSAL ISSUE FOR ANY NEW TREATMENT KEY FOR EVERYDAY ROUTINE:EFECTIVE AND SHORT TRANSMISSION OF CLINICAL TRIALS RESULTS INTO EVERYDAY USE WITH POSITIVE BENEFIT FOR THE PATIENTS.

  14. PART II „Lenalidomide (Revlimid) in myeloma treatment and an assessment of its efficacy“

  15. Lenalidomide (REVLIMID) • Lenalidomide is an attractive drug • Oral agent • Without neurological complications

  16. Thalidomide and Lenalidomide Have Distinct Mechanisms of Action Efficacy of Thalidomide and Lenalidomide Mechanisms of Action1 • + = potency factor of 10 • The mechanism of action of thalidomide is anti-angiogenic, while lenalidomide has more potent tumouricidal and immunomodulatoryeffects1-2 • Regardless of prior exposure to thalidomide, lenalidomide treatment results in significant efficacy with a manageable safety profile 3-4 • Hideshima et al. Blood 2000. • Mitsiades et al. Blood 2002. • Wang M et al. Blood. 2008. • Richardson et al., Blood 2009.

  17. Lenalidomide + Dexamethasone in Relapsed/Refractory Multiple Myeloma Dex: 40 mg,days 1–4, 9–12, 17–20for first four cycles; 40 mg, days 1–4 for subsequent cyclesa Len: 25 mg, days 1–21a Continue untildisease progression Dex: 40 mg,days 1–4, 9–12, 17–20for first four cycles;40 mg, days 1–4 for subsequent cyclesa Placebo:days 1–28a North American MM-009 (48 centres in US, Canada; n = 353)1 International MM-010 (50 centres in Europe, Australia, Israel; n = 351)2 1. Weber DM et al. N Engl J Med. 2007;357:2133-2142. 2. Dimopoulos M et al. N Engl J Med. 2007;357:2123-2132. a Each course of treatment lasted 28 days. Dex, dexamethasone; Len, lenalidomide.

  18. The Tumouricidal Effect of Lenalidomide + HD DexInduces High-Quality ResponsePooled Analysis of Patient Response* from MM-009/0101 • ORR = 60.6% • ORR = ≥ PR • P < .001 • ORR = 21.9% • Patients (%) • Len + Dex (n = 353) • Placebo + Dex (n = 351) . Dimopoulos M et al. Leukemia. 2009;23:2147-2152.

  19. In relapselenalidomideiseffectivewithalllimitationforadvancediseaseOverall Response Rate: up to 60%Time to Progression: + 6-8 monthsOverallSurvival: + 1 year

  20. Response ratebased on pretreatment 1. Newlydiagnosed : ORR – 90-100%2. Firstrelapse: ORR - 50-70%3. Secondrelapse : ORR – 40-50%4. End-stage : ORR - 20-30%

  21. Lenalidomide has strong immunomodulatory feature The maintenance therapy with lenalidomide is beneficial

  22. IFM 2005-02: Study design • Phase III randomized, placebo-controlled trial • N= 614 patients, from 78 centers, enrolled between 7/2006 and 8/2008 • Patients < 65 years, with non-progressive disease,  6 months after ASCT in first line Randomization: stratified according to Beta-2m, del13, VGPR Consolidation: Lenalidomide alone 25 mg/day p.o. days 1-21 of every 28 days for 2 months • Arm B= • Lenalidomide • (N=307) • 10-15 mg/d until relapse • Arm A= • Placebo • (N=307) • until relapse • Primary end-point: PFS. • Secondary end-points: CR rate, TTP, OS, feasibility of long-term lenalidomide…. • ASCT = autologous stem cell transplant. IFM = Intergroupe Francophone du Myelome.

  23. IFM 2005-02 : PFS from randomization • Rev (n =307) • Placebo (n = 307) • P < 10 -8 • P < 10-8 Median follow up: 34 m post rando, 44 m post diag

  24. IFM 2005-02 : PFS .

  25. IFM 2005-02 : OS (to November 2010) .

  26. Limitations !

  27. Safety of the long-term use of lenalidomide (2 years of maintenance – cut off)

  28. Lenalidomide (Revlimid) 25 mg dailyvs. 25 mg everyotherday

  29. PatientswithRevlimidtherapyby 30/06/2010

  30. Treatment • Treatment • Treatment response • Proportion of pts (%) • Proportion of pts (%) • continue • finished • 25 mg daily • 25 mg every other day

  31. Survivalanalysis • OS from diagnosis • OS from start of therapy

  32. Conclusions: Lenalidomide is active and well-tolerated in relapsed/refractory myeloma. These results support the approved 25 mg once-daily dosing regimen of lenalidomide in patients with relapsed/refractory multiple myeloma.

  33. PART III „Objectives and activity of Czech Myeloma Group”.

  34. MainclinicalacitivityLenalidomidebasedtreatment as first line forourpatientsClinical trial ofEeuropeanMyeloma Network

  35. „CMG 2008 junior“Protokol RV-MM-EMN-441a„CMG 2010 senior“Protokol EMN 01

  36. „CMG 2008 junior“Protokol RV-MM-EMN-441 • Maincoordinator: FondazioneNeoplasieSangue Onlus (FO.NE.SA Onlus), Itálie • Coordinatorfor CR, SR,HungaryandPoland: CMG, foundation

  37. JUNIOR protocol design (lenalidomidebasedtreatment) Induction: RD 4 cycles Collectionof PBSC (Cy 3g/m2+ G-CSF) Randomization 1: Arm A: CRD 6 cycles Arm B: ASCT (MEL 200) Randomization 2: Arms: A1, B1: Lenalidomid Arms: A2, B2: Lenalidomid+Prednison

  38. GeneralActual Status Plannednumbersofenrolledpatients: Total: 380 Actual status ofenrollment (31.12.2010): Itály – 233 (and STOP) SlovakRep. – 2 Australia – 34 Hungary – 3 CzechRep. – 49 Poland – 0 Totalof 321 pts. wereenrolleduntil 31.12.2010 Totalof 59 pts. remaining to beenrolled

  39. „CMG 2010 senior“Protokol EMN01 • MainCoordinator: • FondazioneNeoplasieSangue Onlus (FO.NE.SA Onlus), Itálie • CoordinatorforVisegrad: CMG

  40. Design ofthe trial Int. multicentricrandomized trial phase III • Enrollment: 4 years • No. Ofpts.: 660 • Actual status: 331 pts. enrolled

  41. JUNIOR protocol design (lenalidomide based treatment) Randomization 1: Arm A: RD 9 cycles Arm B: MPR Arm C: CPR Randomization 2: Arm A1, B1, C1: Lenalidomid Arm A2, B2, C2: Lenalidomid+Prednison

  42. Where we are going ? There is evidence that new drugs can significantly change prognosis of more than 60% of patients who can t benefit from autologous transplantation as primary treatment

  43. How can patient organizations help? It is very important, if any of evalauted therapies is considered as new perspective treatment. The more important is, if the most patients can benefit from this treatment in the short time period.Rapid introduction of new effective therapeutic strategy is the place for active patient organizations.

  44. Thank you for you attention

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