Dalla terapia ad alte dosi alla talidomide e agli inibitori del proteasoma: una storia terapeutica...

Dalla terapia ad alte dosi Dalla terapia ad alte dosi alla talidomide alla talidomide

e agli inibitori del proteasoma: e agli inibitori del proteasoma: una storia terapeutica in evoluzioneuna storia terapeutica in evoluzione

Roma, 3 febbraio 2006Roma, 3 febbraio 2006

Targeted therapies nella pratica clinica delle neoplasieTargeted therapies nella pratica clinica delle neoplasie

ematologiche - Mieloma multiploematologiche - Mieloma multiplo

DIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALY

Maria Teresa AmbrosiniMaria Teresa Ambrosini

MM* (all 3 criteria required) Monoclonal plasma cells in the bone marrow 10% and/or

presence of a biopsy-proven plasmacytoma

Monoclonal protein present in the serum and/or urine†

Myeloma-related organ dysfunction (1 or more)Myeloma-related organ dysfunction (1 or more)††††

(C)(C) Calcium elevation in the blood (serum calcium >10.5 Calcium elevation in the blood (serum calcium >10.5 mg/L mg/L

or upper limit of normal)or upper limit of normal) (R) (R) Renal insufficiency (serum creatinine >2 mg/dL)Renal insufficiency (serum creatinine >2 mg/dL) (A) (A) Anemia (hemoglobin <10 g/dL or 2g <normal)Anemia (hemoglobin <10 g/dL or 2g <normal) (B)(B) Lytic bone lesions or osteoporosisLytic bone lesions or osteoporosis****

Criteria for Diagnosis of MMCriteria for Diagnosis of MM

*Note: These criteria identify Stage IB and Stages II and III A/B myeloma by Durie/Salmon stage. Stage IA becomes smoldering or indolent myeloma; †If no monoclonal protein is detected (nonsecretory disease), then 30% monoclonal bone marrow plasma cells and/or a biopsy-proven plasmacytoma required; ††A variety of other types of end organ dysfunctions can occasionally occur and lead to a need for therapy. Such dysfunction is sufficient to support classification as myeloma if proven to be myeloma related; **If a solitary (biopsy-proven) plasmacytoma or osteoporosis alone (without fractures) are the sole defining criteria, then 30% plasma cells are required in the bone marrow

Durie BGM et al. Hematol J. 2003;4:379DIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALY

Melphalan and Prednisone (MP)Melphalan and Prednisone (MP)

• Conventional chemotherapy in use for over 40 Conventional chemotherapy in use for over 40 yearsyears

• Partial Response: 50-60%Partial Response: 50-60%

• Complete ReComplete Response 1% sponse 1%

• Median Overall Survival 3 yearsMedian Overall Survival 3 years

• Equivalent mortality and survival between MP Equivalent mortality and survival between MP and combination chemotherapyand combination chemotherapy

Myeloma Trialists' Collaborative Group. J Clin Oncol. 1998;16:3832


DOSEDOSE

RE

SP

ON

SE

RE

SP

ON

SE

Melphalan dose-response curveMelphalan dose-response curve


High dose Melphalan with Autologous Stem Cell High dose Melphalan with Autologous Stem Cell TransplantationTransplantation

• Complete ReComplete Response rsponse rate increased from ate increased from 1 - 3% to 30 - 50%1 - 3% to 30 - 50%

• Remission extended from 18 to 30 Remission extended from 18 to 30 monthsmonths

• Overall survival doubled from 30 to 60 Overall survival doubled from 30 to 60 monthsmonths


Randomized studies: High Dose Therapy Randomized studies: High Dose Therapy versusversus Standard ChemotherapyStandard Chemotherapy

1. Attal M et al. N Engl J Med. 1996;335:912. Child JA et al. N Engl J Med. 2003;348:1875

60453015

P=0.03Conventional

Transplant

Ove

rall

Su

rviv

al (

%)

100

75

50

25

Treatment (mo)

IFM901

Transplant

80

25

50

75

100

0

0 20 40 60

Conventional

Treatment (mo)

Ove

rall

Su

rviv

al (

%)

P = 0.04

0

MRC72


For Newly Diagnosed MMFor Newly Diagnosed MM

Attal M et al. N Engl J Med. 2003;349:2495Cavo M et al. Hematol J 2003;4 abstract P 10.2.5Fermand JP et al. Blood. 2001;98 abstract #3387Sonneveld P et al. Blood. 2004;104 abstract #948

Single vs Double ASCTSingle vs Double ASCT

2424110110DoubleDoubleNo No differencedifference

2525

3434

2121110110SingleSingleCavo et alCavo et al

2222

2020

No No differencedifference

3030

2525

Median EFS (mo)

37379999DoubleDouble

55551313148148SingleSingleSonneveld et al Sonneveld et al (HOVON 24)(HOVON 24)

No No differencedifference

42429494SingleSingleFermand et alFermand et al



48484242199199SingleSingleAttal et alAttal et al

Median OS (mo)

CR (%)nASCTStudy

P=NS

P=NS P<0.05


P=NS

P=0.002 P=0.02 P=NS

P=0.03 P=0.01

Multiple MyelomaMultiple MyelomaS

urv

ival

%S

urv

ival

%

100100

5050

Median survival = 3-5-yearsMedian survival = 3-5-yearsDIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALY

Multiple MyelomaMultiple Myeloma

SEEDSEED


SOILSOIL

Bruno B et al. Lancet Oncology 2003;4:379DIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALY

ThalidomideThalidomide• Precise mechanism of action not yet understood Precise mechanism of action not yet understood

Multiple actions:Multiple actions:

• antiangiogenic effects that provide the rationale antiangiogenic effects that provide the rationale for its use in MMfor its use in MM

• immunomodulatory effectimmunomodulatory effect

• apoptotic effectapoptotic effect

• Thalidomide was first shown to be effective as a single Thalidomide was first shown to be effective as a single agent in patiens with relapsed and refractory disease agent in patiens with relapsed and refractory disease

(Singhal S (Singhal S et al. N Engl J Med. 1999;341:1565)

• Numerous subsequent studies have confirmed its Numerous subsequent studies have confirmed its efficacy with a response rate of 30% alone, 50% when efficacy with a response rate of 30% alone, 50% when used in combination with dexamethasone and 70% with used in combination with dexamethasone and 70% with chemotherapy.chemotherapy.


Thalidomide/dexamethasone combination Thalidomide/dexamethasone combination

Cavo

Blood 2005

Ludwig

ASH 2005

Rajkumar

JCO 2006

Study

DVT (15), constipation (9), infections (4),neuropathy (4), deaths (6)

76%13%100 (*)

ToxicityCR+PRCR/nCRNo

DVT (20),neuropathy (7),skin rash (4), deaths (6)63%4% (CR)103 (*)

DVT (5), neuropathy (15), skin rash (7)52%22%60 (*)

(*) in untreated patients(°) in relapsed patients

Palumbo

Hematol J 2004

DVT (2), neuropathy( 20), confusion (8), skin rash (4)52%na120 (°)

na 55%neuropathy, confusion, constipation, sonnolence

Dimopoulos

Ann Oncol 200144 (°)


Thalidomide/Dexamethasone vs Dexamethasone Thalidomide/Dexamethasone vs Dexamethasone in Newly Diagnosed Multiple Myelomain Newly Diagnosed Multiple Myeloma

Phase III Clinical Trial, newly diagnosed MM for whom Phase III Clinical Trial, newly diagnosed MM for whom stem cell transplantation was considerate appropriatestem cell transplantation was considerate appropriate

Thalidomide 200 mg daily p.o. + Dexamethasone 40 mg Thalidomide 200 mg daily p.o. + Dexamethasone 40 mg p.o. on days 1-4, 9-12, 17-20 or Dexamethasone alonep.o. on days 1-4, 9-12, 17-20 or Dexamethasone alone

Every 4 weekEvery 4 week

Rajkumar SV et al. J Clin Oncol 2006;24:1Rajkumar SV et al. J Clin Oncol 2006;24:1

EndpointDex

(n=100)Thal/Dex

(n=99)

42• Disease progression within first 4 mo, %

1.1 1.1 • Median time to response, mo

41 (41)62 (63)• Response rate, n (%)*

*Best response within 4 courses


Thalidomide/Dexamethasone vs Dexamethasone: Thalidomide/Dexamethasone vs Dexamethasone: Drug-Related Adverse EventsDrug-Related Adverse Events

Dex, n (%) (n=102)

Thal/Dex, n (%) (n=102)Drug-Related Adverse Event

21 (21)46 (45)Total

18 (18)35 (34)Any toxicity ≥ grade 4

4 (4)7 (7)Neuropathy ≥ grade 3

0 (0)1 (1)Sinus bradycardia ≥ grade 3

0 (0)4 (4)Rash ≥ grade 3

3 (3)17 (17)DVT ≥ grade 3

Deaths within 4 cycles: Thal/Dex, 7%; Dex, 11%

Rajkumar SV et al. J Clin Oncol 2006;24:1Rajkumar SV et al. J Clin Oncol 2006;24:1


Thalidomide Chemotherapy combinations

(*) in untreated patients(°) in relapsed patients

DVT (4), neutropenia (6), DVT (4), neutropenia (6), thrombocytopenia (6), thrombocytopenia (6),

constipation (4), constipation (4), neuropathy (2) neuropathy (2)

64%10%T-VAD (*)

Vcr + Adria + Dex + THAL39

Zervas

Ann Oncol 2004

Death (4), DVT (17), infection (11),

neuropathy(31)76%28%

MPT MPT (*)

M + P + THALM + P + THAL129

Palumbo

ASH 2005

53%

CR+PR

32%32%

na

CR/nCR ToxicityRegimenNoStudy

Infections (6), Neuropathy (2), constipation (7)

CTD (°)Cy + Dex + THAL

22Garcia-SanzHemat J 2002

Schutt

Eur J Haematol 200531 T-VED (*)

Vcr + Epir + Dex +THAL19% 80%

DVT (8), neutropenia (10), DVT (8), neutropenia (10), infection (7), neuropathy infection (7), neuropathy

(20) (20)

OffidaniHaematologica 2006 50

DVd-T (°)Vcr+AdriaLipo + Dex + THAL 76%76%

DVT (6),neutropenia (8), DVT (6),neutropenia (8), constipation (1), constipation (1), neuropathy (1) neuropathy (1)


Thalidomide With Melphalan and Prednisone in Thalidomide With Melphalan and Prednisone in Elderly Patients With MMElderly Patients With MM

MPT Arm (Median age 72)

Melphalan, 4 mg/m2 (7 days/mo)

Prednisone, 40 mg/m2 (7 days/mo)

Thalidomide, 100 mg/d (continuously)*

(n=129)

MP Arm (Median age 72)

Melphalan, 4 mg/m2 (7 days/mo)

Prednisone, 40 mg/m2 (7 days/mo)

(n=126)

6 courses6 courses

NewlyNewlydiagnosed MM patients, diagnosed MM patients,

aged >65 yr aged >65 yr (n=255 as of 3/05)(n=255 as of 3/05)

*Thalidomide dose reduced to 50% if grade 2 toxicity. Follow-up ≥6 mos.

Palumbo A et al. Blood. 2005;106: abstract #779

Phase III Randomized Controlled TrialPhase III Randomized Controlled Trial


MPT in Elderly Patients With MM: ResponseMPT in Elderly Patients With MM: Response

NS6480OS at 36 mo

<0.00113.629.2Median EFS, mo

<0.001728CR + nCR

4560PR

47

5

2

MP, % (n=126)

<0.001

P value

16CR

76ORR

12nCR

MPT, % (n=129)

Response

Palumbo A et al. Blood. 2005;106: abstract#779

PR (>50%), nCR (IF+), CR (IF-)


Thromboembolism in MPT-Treated Elderly Thromboembolism in MPT-Treated Elderly Patients Reduced With ProphylaxisPatients Reduced With Prophylaxis

0.01.5Arterial occlusion

0.04.6Pulmonary thromboembolism

3.018.4DVT

With Prophylaxis(n=64)

No Prophylaxis(n=65)Adverse Event

Incidence, %

• More DVT with MPT than with MP (More DVT with MPT than with MP (PP=0.003)=0.003)

• DVT prophylaxis: enoxaparin, 0.4 mL/day for 4 monthsDVT prophylaxis: enoxaparin, 0.4 mL/day for 4 months

Palumbo A et al. Blood. 2005;106:abstract #779DIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALY

MP vs MP-Thal and MP vs Mel100 in Newly Diagnosed MM Patients Aged 65–75 Years

Response MP(n=191)

MP-Thal (n=124)

MEL100 (n=121)

PFS 17,1 27,6 19

OS 30,3 > 55 38,6

3nd planned interim analysis 5/2005; median follow-up time = 32.2 months

Facon T et al. Blood. 2005;106 abstract#780

IFM 99-06 Trial Response to Treatment*IFM 99-06 Trial Response to Treatment*


RandomRandom

MPMP

MP + THALMP + THAL

2 VAD 2 VAD CTX 3g/mq CTX 3g/mq MEL100 MEL100 MEL 100 MEL 100

12 courses12 courses

12 courses12 courses

Maintenance With Thalidomide after ASCT

No maintenance Pamidronate,

90 mg/mo

Pamidronate, 90 mg/mo Thalidomide, 100 mg/day

Attal M et al. Blood. 2005;106 abstract #1148


Endpoint No maintenance Pam Thal/Pam P Value

Patients, n 197 195 201

4-yr EFS, % 39 37 50 0.001

4-yr OS, % 86 78 86 ns

• ASCT (MEL140 MEL200) as front line therapy

• Month 3 after 2 ASCT, if no progression

RandomRandom

CC5013 is CC5013 is more potentmore potent and and less toxicless toxic than the parent than the parent compoundcompound

Induces apoptosis in MM cellsInduces apoptosis in MM cells

Decreases binding of MM cells to bone marrow Decreases binding of MM cells to bone marrow stromal cellsstromal cells

– Inhibits cytokine production Inhibits cytokine production (IL-6, VEGF, TNF-alfa)(IL-6, VEGF, TNF-alfa)

– Blocks angiogenesisBlocks angiogenesis

Thalidomide Analog; REVLIMIDThalidomide Analog; REVLIMID™™ (CC5013) (CC5013)


Phase III Trial of Lenalidomide/Dex in Relapsed or Phase III Trial of Lenalidomide/Dex in Relapsed or Refractory MMRefractory MM

Lenalidomide 25 mg d 1–21Placebo d 22–28

Dex 40 mg, d 1–4, 9–12, 17–20

Placebo d 1–28Dex 40 mg, d 1–4, 9–12, 17–20

Same, exceptDex d 1–4

4 COURSES4 COURSES CONTINUECONTINUEUNTIL PDUNTIL PD

International MM-010 (51 Centers Europe/Australia/Israel): Dimopoulos (351 patients)International MM-010 (51 Centers Europe/Australia/Israel): Dimopoulos (351 patients)

Primary endpoint: TTP (by BladPrimary endpoint: TTP (by Bladé criteria)é criteria)

Secondary endpoints: OS, RR, safety, 1Secondary endpoints: OS, RR, safety, 1stst skeletal-related event, PS skeletal-related event, PS

Inclusion criteriaInclusion criteria

≤≤3 prior therapies3 prior therapies

No Dex resistanceNo Dex resistance

Normal liver/renal Normal liver/renal functionfunction

Dimopoulous M et al. Blood. 2005;106 abstract #6DIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALY

Phase III Trial of Lenalidomide/Dex in Relapsed or Phase III Trial of Lenalidomide/Dex in Relapsed or Refractory MMRefractory MM

Endpoint Lenalidomide/Dex

Placebo/Dex P value

Time To Time To ProgressionProgression

13 mo13 mo 5 ,1 mo5 ,1 mo <0.00001<0.00001

Overall Response Overall Response RateRate

58%58% 22%22% <0.001<0.001

An independent commettee closed the study:An independent commettee closed the study:Revlimid superior to DexRevlimid superior to Dex

Dimopoulous M et al. Blood. 2005;106 abstract #6DIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALY

BortezomibBortezomib

DIVISIONE UNIVERSITARIA DI EMATOLOGIADIVISIONE UNIVERSITARIA DI EMATOLOGIAAZIENDA OSPEDALIERA SAN GIOVANNIAZIENDA OSPEDALIERA SAN GIOVANNITORINO, ITALYTORINO, ITALYBruno B et al. Lancet Oncology 2004

The Proteasome: A Target for

Novel Therapies

APEX : Treatment plan

273 treatment days 280 treatment days

1.3 mg/m2 IV pushDays 1, 4, 8, 11 Q3W cycle

8 cycles

1.3 mg/m2 IV pushDays 1, 8, 15, 22 Q5W cycle

4 cycles

3 cycles 5 cycles

40 mg po Days 1–4, 9–12, 17–20 Q5W cycle

40 mg po Days 1–4 Q4W cycle

Randomization

Bortezomib Dexamethasone

Induction

Maintenance

Richardson Richardson et alet al. N Engl J Med 2005;352:2487. N Engl J Med 2005;352:2487


APEX: OutcomeAPEX: Outcome

Time to progression (Time to progression (nn = 669) = 669)1-year survival (1-year survival (nn = 669) = 669)

Endpoint Bortezomib Dexamethasone

Time To ProgressionTime To Progression 6,2 mo6,2 mo 3,5 mo3,5 mo

Overall Survival @ 1yrOverall Survival @ 1yr 80%80% 66%66%



APEX: response rates (CR, PR)APEX: response rates (CR, PR)

Median time to response (TTR)• 43 days in both armsDuration of response• Bortezomib 8.0 months• Dexamethasone 5.6 months• Median follow-up ~8.3 months

<1% nCR 25% PR

16% PR7% nCR6% CR

Bortezomib Dexamethasone

Res

po

nse

(%

)

38%

18%

P<.0001

0

10

20

30

40

50

60

70

80

90

100

<1% CR



APEX: Treatment-emergent ≥ grade 3 AEs reported by ≥ 5% of patients

Patients %Patients %00 1010 2020 3030 4040 5050

Thrombocytopenia

Neutropenia

Anemia

Peripheral neuropathy

Diarrhea

Fatigue

Dyspnea

Pneumonia

Hyperglycemia

Bortezomib (n = 331) Dexamethasone ( (nn = 332) = 332)



Bortezomib alone and in combination with Dexamethasone for untreated MM

Treatment• Bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11 of

21-day cycle• Dexamethasone 40 mg P.O. on days 1, 2, 4, 5, 8, 9,

11, 12 added if <PR after 2 cycles or <CR after 4 cycles

Jagannath Jagannath et alet al. Br J of Haematology 2005;129:776. Br J of Haematology 2005;129:776


N= 32 Bortezomib Bortezomib+Dexamethasone

CR 3% 6%

nCR 9% 19%

PR 28% 63%

PAD combination therapy (bortezomib (PS-341), PAD combination therapy (bortezomib (PS-341), Adriamycin and Dexamethasone) for untreated MMAdriamycin and Dexamethasone) for untreated MM

Oakervee Oakervee et alet al. Br J of Haematology 2005;129:755. Br J of Haematology 2005;129:755


Treatment

• Bortezomib 1.3 mg/m2 IV on days 1, 4, 8, and 11 of 21-day cycle• Dexamethasone 40 mg on days 1-4, 8-11, 15- 18 during cycle 1, days 1-4 cycles 2-4• Doxorubicine 0 - 4,5 – 9 mg/mq on days 1-4

95%95%ORRORR

33%33%PRPR

33%33%VGPRVGPR

5%5%nCRnCR

24%24%CRCR

Response Rate:Response Rate:

VTD (VELCADEVTD (VELCADE®®, Thalidomide, Dexamethasone) as , Thalidomide, Dexamethasone) as Primary Therapy for Newly-Diagnosed MMPrimary Therapy for Newly-Diagnosed MM

Treatment:Treatment:

• Bortezomib 1.0 to 1.9 mg/mBortezomib 1.0 to 1.9 mg/m2 2 days 1, 4, 8, 11 q 28 daysdays 1, 4, 8, 11 q 28 days

• Thalidomide 100-200 mg each eveningThalidomide 100-200 mg each evening

• Dexamethasone 20 mg/mDexamethasone 20 mg/m22 days 1-4, 9-12, 17-20 q 28 days days 1-4, 9-12, 17-20 q 28 days

28- day treatment cycle, 2 cycles28- day treatment cycle, 2 cycles

Institutional experience of 36 patientsInstitutional experience of 36 patients– 92%92% Response rate (CR+PR) Response rate (CR+PR)– PBSC easily collectedPBSC easily collected

Wang Wang et alet al. . Blood Blood 2005;106 Abstract#784 2005;106 Abstract#784


A phase I/II study of Bortezomib plus Melphalan and A phase I/II study of Bortezomib plus Melphalan and Prednisone (V-MP) in Elderly Untreated MM patientsPrednisone (V-MP) in Elderly Untreated MM patients

Mateos Mateos et alet al. . Blood Blood 2005;106 Abstract#786 2005;106 Abstract#786


Treatment

V-MP 9 courses

Four 6-week courses Melphalan p.o. 9 mg/m2 on days 1-4, Prednisone p.o. 60 mg mg/m2 on days 1-4 VELCADE i.v 1,3 mg/m2 days 1, 4, 8, 11, 22, 25, 29, and 32

Five 5-week courses Melphalan p.o. 9 mg/m2 on days 1-4, Prednisone p.o. 60 mg mg/m2 on days 1-4 VELCADE i.v 1,3 mg/m2 days 1, 8, 22, and 29

V-MP: Response RatesV-MP: Response Rates (N=53) (N=53)

After 1st cycle

0%

10%

20%

30%

40%

50%

60%

70%

CR IF- CR IF+ PR

72%

6% 2%

64%

Best response (median 3 cycles)

10%

20%

30%

40%

50%

60%

70%

85%

0%CR IF- CR IF+ PR MR SD

28%

11%

45%

3%13 %

Mateos Mateos et alet al. . Blood Blood 2005;106 Abstract#786 2005;106 Abstract#786


V-MP: ConclusionsV-MP: Conclusions

High Response RateHigh Response Rate

Manageable toxicities: Manageable toxicities: – Neutropenia and thrombocytopenia were the only Gr3 Neutropenia and thrombocytopenia were the only Gr3

eventsevents

Basis for Basis for VISTAVISTA Phase III trial (n=680): VMP vs MPPhase III trial (n=680): VMP vs MP


HOW TO IMPROVE VMP ?HOW TO IMPROVE VMP ?

V-MPTV-MPTBortezomib + Melphalan + Bortezomib + Melphalan + Prednisone + ThalidomidePrednisone + Thalidomide


Protocol GIMEMA-MM-03-05Protocol GIMEMA-MM-03-05


A PHASE III, MULTI-CENTER, RANDOMIZED OPEN LABEL A PHASE III, MULTI-CENTER, RANDOMIZED OPEN LABEL STUDY OF VELCADE, MELPHALAN, PREDNISONE AND STUDY OF VELCADE, MELPHALAN, PREDNISONE AND

THALIDOMIDE (V-MPT)THALIDOMIDE (V-MPT)

VersusVersus

VELCADE, MELPHALAN, PREDNISONE (V-MP) VELCADE, MELPHALAN, PREDNISONE (V-MP)

IN ELDERLY UNTREATED MULTIPLE MYELOMA IN ELDERLY UNTREATED MULTIPLE MYELOMA PATIENTSPATIENTS

Combinations therapies in Multiple MyelomaCombinations therapies in Multiple Myeloma

Bortezomib + Thalidomide Bortezomib + Thalidomide +/- cytotoxic drugs+/- cytotoxic drugs

M-C

OM

PO

NE

NT

induction

High-dose

relapse

remission


Take home message

• Combinations increase response rate

• Frontline therapy

+ New Drugs


GIMEMA: Italian Myeloma Network1. ALESSANDRIA1. ALESSANDRIA Levis, BaraldiLevis, Baraldi

2. ANCONA2. ANCONA Leoni, OffidaniLeoni, Offidani

3. AOSTA3. AOSTA Di VitoDi Vito

4. ASCOLI PICENO4. ASCOLI PICENO Galieni, BigazziGalieni, Bigazzi

5. ASTI5. ASTI Scassa, CampaScassa, Campa

6. AVELLINO6. AVELLINO Cantore, VolpeCantore, Volpe

7. AVIANO7. AVIANO Tirelli, RupoloTirelli, Rupolo

8. BARI8. BARI Dammacco, LautaDammacco, Lauta

9. BARI9. BARI LisoLiso

10. BERGAMO10. BERGAMO Barbui, GalliBarbui, Galli

11. BIELLA11. BIELLA TonsoTonso

12. 12. BOLOGNA Cavo, TosiCavo, Tosi

13. BOLZANO13. BOLZANO PescostaPescosta

14. BRA14. BRA Vanni, StefaniVanni, Stefani

15. BRESCIA15. BRESCIA Rossi, CrippaRossi, Crippa

16. CAGLIARI16. CAGLIARI Angelucci, CarubelliAngelucci, Carubelli

17. CAGLIARI17. CAGLIARI MantovaniMantovani

18. CAMPOBASSO18. CAMPOBASSO StortiStorti

19. CANDIOLO19. CANDIOLO Aglietta, CapaldiAglietta, Capaldi

20. CATANIA20. CATANIA Giustolisi,Di RaimondoGiustolisi,Di Raimondo

21. CATANZARO21. CATANZARO PiroPiro

22. CATTOLICA22. CATTOLICA Pasquini Pasquini

23. CESENA23. CESENA GuardigniGuardigni

24. CHIOGGIA24. CHIOGGIA BattistaBattista

25. CIRIE'25. CIRIE' Freilone, BeggiattoFreilone, Beggiatto

26. COSENZA26. COSENZA MorabitoMorabito

27. CREMONA27. CREMONA Passalacqua, MorandiPassalacqua, Morandi

28. CREMONA28. CREMONA MorandiMorandi

29. CUNEO29. CUNEO Gallamini, GrassoGallamini, Grasso

30. FIRENZE30. FIRENZE Bosi/NozzoliBosi/Nozzoli

31. FOGGIA31. FOGGIA Ferrandina Ferrandina

32. FOGGIA Monaco

33. FORLI’ Amadori, Gentilini

34. GALLARATE Ciambelli

35. GENOVA Gobbi, Canepa

36. GENOVA Carella

37. LATINA Zapone

38. LECCE Pavone

39. MATERA Ciancio

40. MESSINA Brugiatelli, Mamone

41. MESSINA Musolino

42. MILANO Corradini, Montefusco

43. MILANO Morra

44. MILANO Bregni

45. MODENA Narni

46. MONTEFIASC. Montanaro, Niscola

49. MONZA Pogliani, Rossini

50. NAPOLI Rotoli,Catalano

51. NAPOLI Ferrara

52. NOCERA INF. D’Arco, Califano

53. NOVARA Gaidano, Rossi

54. NUORO Latte, Palmas

55. ORBASSANO Saglio, Guglielmelli

56. PADOVA Semenzato, Zambello

57. PALERMO Mirto, Cangialosi

58. PARMA Rizzoli, Giuliani

59. PAVIA Lazzarino, Corso

60. PERUGIA Liberati, Nunzi

61. PESARO Visani, Leopardi

62. PESCARA Fioritoni, Spadano

63. PIACENZA Cavanna, Lazzaro

64. PINEROLO Griso

65. PISA Petrini/Benedetti

66. POTENZA Ricciuti, Vertone

67. RAVENNA Zaccaria, Molinari

68. REGGIO CAL. Nobile, Callea

69. REGGIO EMILIA Gugliotta,Masini

70. RIMINI Pasquini, Fattori

71. ROMA Annino, Bongarzoni

72. ROMA Andriani

73. ROMA 1 Foà, Petrucci

74. ROMA Cattolica Leone, De Stefano

75. ROMA R.Elena Petti, Pisani

76. ROMA S. Camillo Majolino, De Rosa

77. ROMA T. Vergata Amadori, Caravita, i

78. ROZZANO Santoro, Nozza

79. S. G. ROTONDO Musto, Merla

80. SASSARI Longinotti, Dore

81. SIENA Lauria, Gozzetti

82. TARANTO Mazza, Casulli

83. TORINO 1 Boccadoro, Palumbo

84. TORINO 2 Gallo, Pregno

85. TORINO MAURIZ. Poccardi, Gottardi

86. TORINO S. VITO Marinone, Ficara

87. TREVISO Foscolo, Gherlinzoni

88. TRIESTE De Sabbata

89. UDINE Fanin, Patriarca

90. VARESE Pinotti

91. VENEZIA Chisesi

92. VERBANIA Montanara, Luraschi

93. VERONA Pizzolo, Meneghini

94. VICENZA Rodeghiero, Elice

Dalla terapia ad alte dosi alla talidomide e agli inibitori del proteasoma: una storia terapeutica...

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