Revlimid ® (lenalidomide), Melphalan and Prednisone (R-MP) Gimema: Italian Myeloma Network Antonio...

RevlimidRevlimid®® (lenalidomide), Melphalan (lenalidomide), Melphalan and Prednisone (R-MP)and Prednisone (R-MP)

Gimema: Gimema: Italian Myeloma NetworkItalian Myeloma Network

Antonio PalumboAntonio PalumboDept. Hematology, University of Torino

Multicenter Phase I/II TrialMulticenter Phase I/II Trial Newly Diagnosed PatientsNewly Diagnosed Patients

Age >65 YearsAge >65 Years

Disclosures for (Antonio Palumbo, M.D.)

N/A = Not Applicable (no conflicts listed)

Presentation includes discussion of the following off-label use of a drug or medical device.

<Lenalidomide, Thalidomide>

Celgene. Pharmion.Celgene. Pharmion.Scientific Advisory BoardScientific Advisory Board

Celgene, Pharmion.Celgene, Pharmion.Speakers’ BureauSpeakers’ Bureau

(N/A for no conflict or name of company)(N/A for no conflict or name of company)Major StockholderMajor Stockholder

Celgene, Pharmion.Celgene, Pharmion.ConsultantConsultant

(N/A for no conflict or name of company)(N/A for no conflict or name of company)EmployeeEmployee

(N/A for no conflict or name of company)(N/A for no conflict or name of company)Research Support/P.I.Research Support/P.I.

In compliance with ACCME policy, the ASCO requires the following disclosures to the activity audience:

Rationale

54%

MP

5.0

DEX

12.2

DEX

MPTDiagnosis(3)

P<0.00115.1EFS (months)

REV-DEXRelapse(2)

P<0.001*21.1 EFS (months)

27%

MP

P=0.0006EFS @ 2 years

Diagnosis(1)

*P<0.001 for pts not receiving Melphalan

(1) Facon T et al. Blood. 2006;107:1292. (2) Palumbo A et al. Lancet. 2006;367:825. (3) Dimopoulos M et al. Blood. 2005;106:6a [abstract 6]

Dept. Hematology, University of Torino

1 2 3 4 21

Revlimid® 5–10 mg/day, continuously until relapse

Mel 0.18–0.25 mg/Kg

Prednisone 2 mg/Kg

Every 4–6 weeks for a maximum of 9 cyclesEvery 4–6 weeks for a maximum of 9 cycles

day

Melphalan mg/Kg/dMelphalan mg/Kg/d RevlimidRevlimid®® mg/d mg/d PatientsPatients

Cohort 1Cohort 1 0.18 5 6

Cohort 2Cohort 2 0.25 5 6

Cohort 3Cohort 3 0.18 10 6+15

Cohort 4Cohort 4 0.25 10 6+15

6 patients in each cohort with additional 15 pts in cohort 3 and 4

Treatment Schedule


Patient Characteristics

No. of patients 5353

Median age (range)Median age (range) 71 (57–77)71 (57–77)

65–70 years65–70 years 43%

71–75 years71–75 years 51%

Chromosome Deletion (13 q)Chromosome Deletion (13 q) 38%ß2-mß2-microglobulinicroglobulin mg/L ( mg/L (medianmedian)) 3.4

Hemoglobin g/L (median)Hemoglobin g/L (median) 12.0

Creatinine mg/dL (median)Creatinine mg/dL (median) 1.0

Ca++ mmol/L (median)Ca++ mmol/L (median) 2.41


Dose Limiting Toxicity

3/63/61/61/60/60/60/60/6Pts with DLTPts with DLT

1/6

1/6

1/6

Cutaneous GR 3

Thrombosis GR 4

Metabolic GR 3

2/6Delay at cycle 2

1/6Neutropenia fever

1/6Severe Neutropenia

Cohort 40.25–10

Cohort 30.18–10

Cohort 20.25–5

Cohort 10.18–5DLT at Cycle 1


Cohort 3 (0.18-10) [N=21]Cohort 3 (0.18-10) [N=21] Cohort 4 (0.25-10) [N=20]Cohort 4 (0.25-10) [N=20]

00 1010 2020 3030 4040 5050 6060

% Patients% Patients

NeutropeniaNeutropenia

ThrombocytopeniaThrombocytopenia

AnemiaAnemia

G-CSFG-CSF

Hematologic Toxicity Grade 3–4 Adverse Events

7070


0 2 4 6 8 10 12

Thrombosis

Infections

NeutropenicFever

Cutaneous


Cohort 3 (0.18-10) [N=21]Cohort 3 (0.18-10) [N=21] Cohort 4 (0.25-10) [N=20]Cohort 4 (0.25-10) [N=20]

Non-Hematologic Toxicity Grade 3–4 Adverse Events


Cycle 1-2 [N=41] Cycle 5-6 [N=34]


NeutropeniaNeutropenia

ThrombocytopeniaThrombocytopenia

AnemiaAnemia

Infection and Infection and neutropenic feverneutropenic fever

CutaneousCutaneous

ThrombosisThrombosis

00 1010 2020 3030 4040

Grade 3–4 Adverse Events

5050


Thromboembolism

R-MP (n=41)

MPT(n=64)

MPT(n=65)

Aspirin100 mg/d

Enoxaparin40 mg/d

No Prophylaxis

DVT 2.4%* 3% 18.4%

Pulmonary Thromboembolis 2.4% 0% 4.6%

Arterial Occlusion 0% 0% 1.5%

Total 4.8% 3% 24.5%

*DVT occurred after aspirin discontinuation*DVT occurred after aspirin discontinuation


R-MP vs MP: Response RateAfter 1 cycle R-MP (N=41) After 6 cycles MP (N=126)*

Historical control

17.5%

27.5%

62.5%

2.5%0%0

10

20

30

40

50

60

70

CR VGPR PR MR SD-PD

%

92.5%92.5% 64.4%64.4%

31.8%

16.7%

35.7%

2.4%

0

10

20

30

40

50

60

70

CR VGPR PR MR SD-PD

9.6%

%

*Lancet 2006;367:825


R-MP vs MPT: Response RateR-MP (N=41)*

Median 7 cycles (2-9)

MPT (N=129)*^Historical control

81.3%81.3%100%100%

0%

14.6%

43.9%

24.4%

17.1%

05

101520253035404550

CR VGPR PR MR SD-PD

%

13.2%

5.4%

39.5%

20.9%

15.5%

0

5

10

15

20

25

30

35

40

45

CR VGPR PR MR SD-PD

%

*Best response*Best response ^Lancet 2006;367:825


R-MP: Response RateCohort 3 (0.18-10) [N=21]*

Median 7 cycles (4-9)Cohort 4 (0.25-10) [N=20]*

Median 5 cycles (2-9)

0%

14.3%

33.3%28.5%

23.8%

0

10

20

30

40

50

60

CR VGPR PR MR SD-PD

%

100%100% 100%100%

0%

15%

55%

20%

10%

0

10

20

30

40

50

60

CR VGPR PR MR SD-PD

%

*Best response*Best response


Event-Free Survival

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 2 4 6 8 10 12 14 16 18 20

R-MPR-MP

MPTMPTHistorical controlHistorical control

87%@16 months 87%@16 months

71%@18 months 71%@18 months

% o

f p

atie

nts

%

of

pat

ien

ts

MPT: median follow-up 17.6 months (0.23-44.3) [N=129]MPT: median follow-up 17.6 months (0.23-44.3) [N=129]

R-MP: median follow-up 9.6 months (5.7-16.6) [N=53]R-MP: median follow-up 9.6 months (5.7-16.6) [N=53]

months months


Conclusions• Early deaths 0%

• Grade 3/4 Adverse Events (incidence >5%)

– Neutropenia 66%

– Thrombocytopenia 34 %

– Anemia 17 %

– Cutaneous 10 %

– Neutropenic Fever 8%

• Response Rate (median 7 cycles)

– CR + VGPR 41%

– CR + PR 85 %

– CR + PR + MR 100 %


BRESCIA Dr. Rossi, Dr. Crippa

CATANIA Prof. Giustolisi, Prof. Di Raimondo

COSENZA Prof. Morabito

GENOVA Prof. Gobbi, Dr. Canepa

MILANO Prof. Corradini, Dr. Montefusco

PARMA Prof. Rizzoli, Dr. Giuliani

ROMA 1 Prof. Foà, Dr. Petrucci

S. G. ROTONDO Dr. Musto, Dr. Falcone

SIENA Prof. Lauria, Dr. Gozzetti

TORINO 1 Prof. Boccadoro, Dr. Falco

We Are Grateful to all Patients, Nurses and Physicians of the Participating Centers

Revlimid ® (lenalidomide), Melphalan and Prednisone (R-MP) Gimema: Italian Myeloma Network Antonio...

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Transcript of Revlimid ® (lenalidomide), Melphalan and Prednisone (R-MP) Gimema: Italian Myeloma Network Antonio...