AntraciclineAntracicline liposomialiliposomiali vsvsliposomialiliposomiali peghilatepeghilate nel MM: nel MM:

esperienze a confrontoesperienze a confronto

Massimo OffidaniMassimo Offidani

Clinica di EmatologiaClinica di EmatologiaAzienda Azienda Ospedaliero-UniversitariaOspedaliero-Universitaria

Ospedali Riuniti di AnconaOspedali Riuniti di Ancona

EffectEffect of single of single drugdrug doxorubicin in MM doxorubicin in MM

9 rel/ref MM pts: 1 PR and 1 MR(Alberts DS et al: Cancer Chem Rep, 1975)

Review of literature rel/ref MM: 5% PR(Rodjer S et al: Haemat J, 2000)

EffectEffect of doxorubicin of doxorubicin combinationscombinations in MM in MMVAD: PR=50-65%, VGPR=15%, CR/nCR=4-8%

AnthracyclinesAnthracyclines in Multiple Myeloma in Multiple Myeloma

•• DoxorubicinDoxorubicin isis one of the one of the mostmost potentpotent antibioticsantibiotics usedused in in

tumor tumor chemotherapychemotherapy

•• Short Short halfhalf life life havehave negative impact on the negative impact on the

administrationadministration modalitymodality

•• LongerLonger exposureexposure toto higherhigher concentrationsconcentrations resultsresults in in

higherhigher plasma plasma cellcell killkill

•• Total cumulative Total cumulative effecteffect limits limits itsits useuse in in chronicchronic diseasedisease

processesprocesses

((MyocetMyocet, , DaunoxomeDaunoxome))ConventionalConventional Liposomal Liposomal DoxorubicinDoxorubicin

CattelCattel L et al. L et al. TumoriTumori. 2003. 2003

IncapsulazioneIncapsulazione in in liposomaliposoma stabile stabile = il farmaco rimane nei = il farmaco rimane nei liposomiliposomi finchèfinchènon raggiunge un tessuto permeabile (tumore)non raggiunge un tessuto permeabile (tumore)

StealthStealth (denso strato di gruppi carboidrati) (denso strato di gruppi carboidrati)= invisibile al RES= invisibile al RES

PegilazionePegilazione== lento rilascio e picco ridotto farmaco libero lento rilascio e picco ridotto farmaco libero

Pegylated Liposomal Pegylated Liposomal DoxorubicinDoxorubicin((CaelyxCaelyx or Doxil) or Doxil)

CattelCattel L et al. L et al. TumoriTumori. 2003. 2003

Minore esposizione tessuti saniMinore esposizione tessuti saniMaggiore esposizione tumoreMaggiore esposizione tumore

Minore suscettibilità MDRMinore suscettibilità MDR

Minore tossicitàMinore tossicitàMaggiore efficaciaMaggiore efficacia

Pegylated Liposomal Pegylated Liposomal DoxorubicinDoxorubicin((CaelyxCaelyx or Doxil) or Doxil)

CattelCattel L et al. L et al. TumoriTumori. 2003. 2003

CardiotossicitàCardiotossicità

RationaleRationale forfor Pegylated PegylatedLiposomal Liposomal DoxorubicinDoxorubicin in MM in MM

•• IncreasedIncreased angiogenesisangiogenesis in BM of MM in BM of MM patientspatients

•• LongerLonger plasma plasma halfhalf life life

•• PossiblePossible more more effectiveeffective againstagainst MDR positive MDR positive cellscells

•• ImprovedImproved safetysafety profileprofile comparedcompared toto freefree doxorubicindoxorubicin

•• OutpatientOutpatient regimenregimen

•• CAELYX has a CAELYX has a favorablefavorable safetysafety profileprofile•• Phase III Phase III DVdDVd vsvs VAdVAd

–– RR, PFS, OS RR, PFS, OS similarsimilar•• SignificantlySignificantly lessless neutropenianeutropenia (10 (10 vsvs 24%) 24%)•• AlopeciaAlopecia (20 (20 vsvs 44%) 44%)•• LessLess supportivesupportive carecare (CVA, (CVA, GFsGFs))

–– DVdDVd regimenregimen decreaseddecreased angiogenicangiogenic activityactivity in BM in BM•• NeedNeed forfor modifyingmodifying anthracycline-basedanthracycline-based regimensregimens withwith thethe

additionaddition of of new-drugsnew-drugs–– ThalidomideThalidomide, , LenalidomideLenalidomide–– BortezomibBortezomib

Rifkin et al. Rifkin et al. CancerCancer. 2006;106:848-858. 2006;106:848-858Hussein et al. Hussein et al. ClinClin Lymphoma Myeloma Lymphoma Myeloma. 2007;7(suppl 4):S145-S149. 2007;7(suppl 4):S145-S149

Why CAELYX in Multiple Myeloma?

PreclinicalPreclinical rationalerationale forfor Pegylated Liposomal Pegylated LiposomalDoxorubicinDoxorubicin + + IMiDsIMiDs in MM in MM

Different but complementary mechanism of actionDifferent but complementary mechanism of action

•• Both Both antiangiogenicantiangiogenic

•• Both Both cytotoxiccytotoxic effect with different mechanism effect with different mechanism

•• IMiDsIMiDs target microenvironment target microenvironment

•• IMiDsIMiDs exert immune activation effect exert immune activation effect

•• NonoverlappingNonoverlapping toxicities toxicities

Preclinical Rationale for CombiningPreclinical Rationale for CombiningCAELYX + CAELYX + BortezomibBortezomib

•• Additive or synergistic effects are seen in both Additive or synergistic effects are seen in both ininvitrovitro1,2,31,2,3 and and in vivoin vivo44 model systems model systems

•• Interactions occur through multiple pathways toInteractions occur through multiple pathways toenhance anti-tumor efficacyenhance anti-tumor efficacy

–– BortezomibBortezomib abrogates abrogates anthracyclineanthracycline resistance resistance

•• NF-kB NF-kB1,21,2, Bcl-2, P-glycoprotein, DNA damage, Bcl-2, P-glycoprotein, DNA damagerepairrepair33

–– AnthracyclinesAnthracyclines abrogate abrogate bortezomibbortezomib resistance resistance

•• Suppression of stress response protein MKP-1Suppression of stress response protein MKP-144

1Mark et al. Clin Cancer Res. 2003;9:1136-1144; 2Mitsiades et al. Blood. 2003;101:2377-2380;3Hideshima et al. Blood. 2003;101:1530-1534; 4Small et al. Mol. Pharmacol. 2004;66:1478-1490.

CAELYX in relapsed/refractory MMCAELYX in relapsed/refractory MM

No No ptspts

222244

626250505050

30330318182828232344442020

AutorAutor

OrlowskiOrlowski ((BloodBlood 05) 05)ChariChari (ASH 05) (ASH 05)BazBaz ( (AnnAnn OncolOncol 06) 06)OffidaniOffidani ( (HaematologicaHaematologica 06) 06)HusseinHussein ((MayoMayo ClinClin ProcProc 06) 06)OrlowskiOrlowski (JCO 07) (JCO 07)JakubowiakJakubowiak (ASH 07)(ASH 07)PalumboPalumbo ((AnnAnn OncolOncol 08) 08)Chanan-KhanChanan-Khan ( (LeukLeuk LymphLymph 09) 09)OffidaniOffidani (SIE 09) (SIE 09)WatermanWaterman (ASCO 09) (ASCO 09)

StudyStudy phasephase

I/III/III/III/IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII

retrospretrosp

RegimenRegimen

B-PLDB-PLDMBDoxilMBDoxilDVd-RDVd-RThaDDThaDDDVd-TDVd-T

V-DoxilV-Doxil vsvs V VVDDVDD

PADoxilPADoxilVDTVDT

ThaDD-VThaDD-Vreducedreduced DVD DVD

624624

CAELYX in newly diagnosed MMCAELYX in newly diagnosed MM

AutorAutor

DimopoulosDimopoulos ( (AnnAnn OncolOncol 03) 03)HusseinHussein ( (MayoMayo ClinClin ProcProc 06) 06)OffidaniOffidani ( (BloodBlood 06) 06)RifkinRifkin ( (CancerCancer 06) 06)ZervasZervas ( (AnnAnn OncolOncol 07) 07)Chanan-KhanChanan-Khan (ASH 07)(ASH 07)PalumboPalumbo (JCO 09) (JCO 09)JakubowiakJakubowiak (JCO 09) (JCO 09)BazBaz (ASCO 09) (ASCO 09)JakubowiakJakubowiak (ASCO 09) (ASCO 09)

StudyStudy phasephase

IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII

I/III/II

RegimenRegimen

VAD VAD bolusbolus vsvs VAD VAD doxildoxilDVd-TDVd-TThaDDThaDD

DVdDVd vsvs VAdVAdVADdoxilVADdoxil vsvs T-VADdoxilT-VADdoxil

VDTVDTPAD-Mel100PAD-Mel100

VDDVDDRDDRDD

R-VDDR-VDD

No No ptspts

132132525250509797

1171172323

102102404031312323

667667

CaelyxCaelyx + + new-drugsnew-drugs nel MM nel MM

allall’’esordioesordio

CaelyxCaelyx 40 mg/m 40 mg/m22

everyevery 28 28 daysdays

Interferon-aInterferon-a 3 MU x 3/ 3 MU x 3/weekweekDesametasone 20 mg x 4 Desametasone 20 mg x 4 daysdays//monthsmonths

ThaDD ThaDD regimenregimen (2003) (2003)

11 22 33 44 55 66 77 9988 11111010 1212

Dexamethasone 40Dexamethasone 40mg/daymg/day

Dexamethasone 40Dexamethasone 40mg/daymg/day

Thalidomide 100 mg day continuously

R

ThalidomideThalidomide 100 mg/day 100 mg/dayDesametasone 20 mg x 4 Desametasone 20 mg x 4 daysdays//monthsmonths

ResponseResponse ≥≥ MR MR

Caratteristiche dei 100 pazienti allCaratteristiche dei 100 pazienti all’’esordioesordio

CaratteristicheCaratteristiche

EtàEtà

ISS II-IIIISS II-III

PS (WHO)PS (WHO) ≥≥22

InsuffInsuff. renale. renale

ββ2-microglobulina2-microglobulina

≥≥ 3.5 3.5 mg/dlmg/dl

PCR > range normalePCR > range normale

Cariotipo sfavorevoleCariotipo sfavorevole

Masse extramidollariMasse extramidollari

NN

7878

3333

2323

5656

3535

2525

88

Mediana (range)Mediana (range)

7272 (45-91)(45-91)

3.8 (0.4-30)3.8 (0.4-30)

Risposta esordio Risposta esordio

≥≥ PR = PR = 93% 93%

≥≥ VGPR = VGPR = 67% 67%

CR+nCRCR+nCR = = 38% 38%

Risposta dopo 6 cicliRisposta dopo 6 cicli

CRCR

nCRnCR

VGPRVGPR

PRPR

RMRM

ProgressioneProgressione

DecessoDecesso

TotaleTotale

N°N°

2929

99

2929

2727

22

11

33

100100

ProgressionProgression freefree survivalsurvival and and responseresponse CR: CR: medianmedian = 43 m = 43 m

nCR+VGPRnCR+VGPR: : medianmedian = 32 m = 32 m

PR: PR: medianmedian = 16 m = 16 m

CR CR vvss nCR+VGPR+PR:nCR+VGPR+PR:MedianMedian PFS = PFS = 43 43 vsvs 22 22 monthsmonths

5-yrs= 5-yrs= 31%31% vsvs 9%9%p= 0.031p= 0.031

ProgressionProgression freefree survivalsurvival and and responseresponse

OverallOverall survivalsurvival

MedianMedian OS = OS = 56 56 monthsmonths

3 3 yrsyrs OS = OS = 69% 69%

5 5 yrsyrs OS = OS = 43% 43%

ThaDD: side ThaDD: side effectseffectsTipoTipo

StipsiStipsiAsteniaAsteniaEdemaEdemaRashRash cutaneo cutaneoNeuropatiaNeuropatiaTVP/EPTVP/EPInfezioniInfezioniPPEPPEMucositeMucosite orale oraleEventi cardiaci Eventi cardiaci ischemiciischemici

NeutropeniaNeutropeniaPiastrinopeniaPiastrinopenia

Grado 3Grado 3

7 7 77442277

11111212331111

7700

Grado 4Grado 4

00000000002244111122

1111

ThaDD: ThaDD: compliancecompliance

Interruzione Interruzione Desametasone=Desametasone= 1 1Miopatia severaMiopatia severa

Interruzione Interruzione Caelyx=Caelyx= 1 1PPEPPE

Interruzione protocollo=Interruzione protocollo=88Eventi cardiaci Eventi cardiaci ischemici=ischemici= 3 3

EP= 2EP= 2

Shock settico= 1Shock settico= 1

MucositeMucosite severa= 1 severa= 1

Scompenso metabolico +FA= 1Scompenso metabolico +FA= 1

Interruzione Thal= 12Rash cutaneo= 2

Neuropatia= 7

TVP= 1

Tremore= 1

Stipsi= 1

RiskRisk of of withdrawalwithdrawal fromfrom protocolprotocol

10%10%

Confronto regimi MM dellConfronto regimi MM dell’’anzianoanziano

ThaDDThaDD(Offidani)(Offidani)

100100

7272

2828

2626

5454

8383

3131

88

MPT*MPT*(Palumbo)(Palumbo)

129129

7272

2020

1616

5454

8383

3939

1616

N pazientiN pazienti

Età mediana (anni)Età mediana (anni)

>75 anni (%)>75 anni (%)

CRCR

2-yrs PFS (%)2-yrs PFS (%)

2 2 yrsyrs OS (%) OS (%)

ToxTox non-ematologicanon-ematologica

ToxTox ematologica ematologica

MPTMPT@@

(Facon)(Facon)

125125

7070

00

1313

6161

8585

3333

4848

VMPVMP$$

(San (San MiguelMiguel))

344344

7171

3131

3535

NANA

82.582.5

4646

4040

MPRMPR(Palumbo)(Palumbo)

5454

7171

66

2424

6161

9090

3030

6868

CaelyxCaelyx: 3-4 : 3-4 drugdrug combinationscombinations

PADPADPalumboPalumbo

102102

6767

9696

6060

7878

8484

2727

2626

VDDVDDJakubowiakJakubowiak

4040

6161

8585

57.557.5

8080

9292

1010

37.537.5

VDTVDTChanan-KanChanan-Kan

2323

6060

6565

nana

nana

nana

nana

nana

RDDRDDBazBaz

3131

6464

8080

4040

nana

nana

4848

3030

ThaDDThaDDOffidaniOffidani

100100

7272

9393

6767

5454

8383

88

3636

RVDDRVDDJakubowiaJakubowia

kk

2323

6464

9595

4747

nana

nana

1010

1515

No of No of ptspts

MedianMedian ageage

ORR (%)ORR (%)

≥≥VGPRVGPR (%) (%)

2 2 yrsyrs PFS (%) PFS (%)

2-yrs2-yrs OS (%) OS (%)

Max Max haemathaemat toxicitytoxicity

Non-haematNon-haemat toxicitytoxicity

PAD-Mel100-LP-LPAD-Mel100-LP-L

Palumbo A, JCO 2009, in pressPalumbo A, JCO 2009, in press

VelcadeVelcade 1.3 mg/ 1.3 mg/mqmq gggg 1, 4, 15, 18 1, 4, 15, 18Doxil 30 mg/Doxil 30 mg/mqmq gggg 4 4Desametasone 40 mg Desametasone 40 mg gggg 1-4, 8-11, 15-18 1-4, 8-11, 15-18 ciclociclo 1 e 1 e gggg 1-4 1-4 ciclicicli 2- 2-

4.4.

CTX (3 CTX (3 g/mqg/mq) + G-CSF) + G-CSFDoppioDoppio Mel 100 mg/ Mel 100 mg/mqmq

Lenalidomide 25 mg Lenalidomide 25 mg gggg 1-21+ PDN 50 mg 1-21+ PDN 50 mg gggg alternialterni

Len 10 mg Len 10 mg gggg 1-21 1-21 ogniogni 28 28 gggg

InduzioneInduzione

ASCTASCT

ConsolidamentoConsolidamento

MantenimentoMantenimento

102 patients (median age 67, range 65-75)102 patients (median age 67, range 65-75)

4 PAD4 PAD

≥≥ PR = PR = 96%96%

≥≥ VGPR = VGPR = 60% 60%

CR =CR = 13% 13%

Tandem MEL100Tandem MEL100

≥≥ PR = PR = 99%99%

≥≥ VGPR = VGPR = 82% 82%

CR =CR = 38.5% 38.5%

≥≥ PR = PR = 100%100%

≥≥ VGPR = VGPR = 86% 86%

CR =CR = 66% 66%

Cons-MantCons-Mant LP-L LP-L

Grado 3-4 tossicità ematologica = Grado 3-4 tossicità ematologica = 27%27%Grado 3-4 neuropatia periferica =Grado 3-4 neuropatia periferica = 16% 16%Grado 3-4 infezioni =Grado 3-4 infezioni = 10% 10%

CaelyxCaelyx + + new-drugsnew-drugs nel MM nel MM recidivato/refrattariorecidivato/refrattario

BortezomibBortezomib + CAELYX + CAELYX vsvs BortezomibBortezomibMonotherapyMonotherapy: Study Design: Study Design

BortezomibBortezomib 1.3 mg/m 1.3 mg/m22 days 1, 4, days 1, 4,8, 11 every 21 days8, 11 every 21 days

BortezomibBortezomib as above + as above +CAELYX 30 mg/mCAELYX 30 mg/m22 on day 4 on day 4

StudyStudy Design DesignRelapsedRelapsed oror refractoryrefractory MM MMPhase III, Phase III, multicentermulticenter (123 (123

participatingparticipating centerscenters))EligibilityEligibility2+ 2+ lineslines of of therapytherapyBortezomib-naïveBortezomib-naïveECOG 0-1ECOG 0-1

RANDOMIZATION

N = 646N = 646

Treat until progression, unacceptableTreat until progression, unacceptabletoxicity or max. of 8 cycles (unless diseasetoxicity or max. of 8 cycles (unless diseasestill responding)still responding)

Orlowski et al. J Clin Oncol. 2007;25:3892-3901.

Primary endpoint: TTPPrimary endpoint: TTPSecondary: OS, ORR, safetySecondary: OS, ORR, safety

StratifyStratifyββ22microglobulin (microglobulin (≤≤ 2.5, 2.5,

> 2.5 > 2.5 butbut ≤≤ 5.5, > 5.5) 5.5, > 5.5)Response Response vsvs progressionprogression to to priorprior treatmenttreatment

Response RateResponse Rate

BortezomibBortezomib(n = 322)(n = 322)

CAELYX +CAELYX +BortezomibBortezomib(n = 324)(n = 324)

P-valueP-value

TotalTotal(CR + (CR + nCRnCR + PR) + PR) 41%41% 44%44% .43.43

CRCRnCRnCR

2%2%8%8%

4%4%9%9%

PRPR 39%39% 40%40%

CR + VGPR CR + VGPR 19%19% 27%27% .0157.0157

Orlowski et al. J Clin Oncol. 2007;25:3892-3901.

Time-to-Progression

Orlowski et al. J Clin Oncol. 2007;25:3892-3901

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No 70 Chromosome 13 deletion:

Cytogenetic abnormality:

Prior thalidomide/lenalidomide:

Prior anthracycline use:

Prior stem cell transplantation:

Baseline ECOG:

Response to prior treatment:

β2

-microglobulin (mg/L):

Sex:

Age (years):

Region:All Patients:

YesNo

YesNo

YesNo

YesNo

Yes10

NoYes

>5.5>2.5 & ≤5.5

≤2.5Female

Male

≥65<65

Non-USAUSA

4714111737826821043628735936028456

59019739590

28336325039660541

646

Subgroup N

1.890.941.711.622.011.621.831.881.941.761.672.182.991.752.111.831.022.061.671.821.751.803.071.82

(0.78, 4.58)(0.32, 2.76)(0.95, 3.08)(0.83, 3.18)(1.42, 2.84)(1.08, 2.41)(1.12, 3.00)(1.38, 2.55)(1.30, 2.87)(1.25, 2.50)(1.20, 2.33)(1.43, 3.32)(1.05, 8.54)(1.35, 2.29)(1.36, 3.28)(1.30, 2.58)(0.45, 2.29)(1.37, 3.09)(1.19, 2.34)(1.19, 2.79)(1.26, 2.45)(1.38, 2.34)(0.71,13.22)(1.41, 2.35)

HR

Hazard Ratio (Bortezomib vs. CAELYX + Bortezomib) & 95% CI (Log Scale)

0.2 0.5 1 3 7Favoring

CAELYX + BortezomibFavoring

Bortezomib

.

Subgroup Analyses

Selected Adverse Events of Interest

BortezomibBortezomib(n = 318)(n = 318)

CAELYX +CAELYX +BortezomibBortezomib

(n = 318)(n = 318)

TotalTotal GradeGrade3/43/4 TotalTotal Grade 3/4Grade 3/4

Peripheral neuropathyPeripheral neuropathy 39%39% 9%9% 35%35% 4%4%

Febrile Febrile neutropenianeutropenia 2%2% 2%2% 3%3% 3%3%

Bleeding/hemorrhageBleeding/hemorrhage 9%9% 1%1% 14%14% 4%4%ThromboembolicThromboemboliceventsevents 1%1% 1%1% 1%1% 1%1%

Cardiac eventsCardiac events 7%7% 3%3% 10%10% 2%2%

AlopeciaAlopecia 1%1% 00 2%2% 00

Orlowski et al. J Clin Oncol. 2007;25:3892-3901.

Risposta terapiaRisposta terapia≥≥ VGPR= 36% VGPR= 36% vsvs 15% (p= 0.018) 15% (p= 0.018)

≥≥ nCR=nCR= 30% 30% vsvs 10.5% (p= 0.022) 10.5% (p= 0.022)

European Journal of Hematology, 2007European Journal of Hematology, 2007

2-yrs EFS: 44% vs 23%

Dex: 20 mg/d

Thal: 100 mg/d (ameneded to 50 mg)

Bort: 1.3 mg/m2 (amended to 1, 4, 11)

Doxil: 30 mg/m2

1 2 4 5 8 9 11 12 14 28

Thalidomide

Day

D D D DBB BB BB BB

D

INDUCTIONINDUCTION

CONSOLIDATIONCONSOLIDATION

1 2 4 5 8 9 11 12

D D D DBB BB BB BB

20 mg/d (amended to 1,2 and 8,9)

1 mg/m2 (amended to 1 and 8)

Day

1 2 3 4 28

D

Thalidomide 100 mg/d

20 mg/d

6 ALTERNATING6 ALTERNATINGCYCLES EVERYCYCLES EVERY

28 DAYS28 DAYS

MAINTENANCEMAINTENANCE

Thalidomide 100 mg/d (amended to 50 mg/d)

ThaDD-VThaDD-V

ThaDD-VThaDD-VThalidomideThalidomide 100 mg/die 100 mg/die

Desametasone 20 mg giorni 1,2 - 4,5 - 8,9 - 11,12Desametasone 20 mg giorni 1,2 - 4,5 - 8,9 - 11,12

CaelyxCaelyx 30 mg/m 30 mg/m22 giorno 4 giorno 4

VelcadeVelcade 1.3 mg/m 1.3 mg/m22 giorni 1, 4, 8, 11 giorni 1, 4, 8, 11

Offidani Offidani etet al, EHA 2009 al, EHA 2009

My-VTDMy-VTDThalidomideThalidomide 100 mg/die 100 mg/die

Desametasone 24 mg giorni 1,2 - 4,5 - 8,9 - 11,12Desametasone 24 mg giorni 1,2 - 4,5 - 8,9 - 11,12

MyocetMyocet 30-50 mg/m 30-50 mg/m22 giorno 4 giorno 4

VelcadeVelcade 1.0 mg/m 1.0 mg/m22 giorni 1, 4, 8, 11 giorni 1, 4, 8, 11

CiolliCiolli etet al , BJH 2008 al , BJH 2008

ThaDD-VThaDD-V vsvs My-VTDMy-VTD: caratteristiche pazienti: caratteristiche pazienti

ThaDD-VThaDD-V

(44 (44 ptspts))

63.5 (31-83)63.5 (31-83)

31 (74)31 (74)

6 (14)6 (14)

13 (29)13 (29)

22 (1-6) (1-6)

1919 (43)(43)

7 (16)7 (16)

20 20 (48)(48)

CaratteristicheCaratteristiche

Età medianaEtà mediana

ISS II-IIIISS II-III

InsuffInsuff. renale. renale

Citogenetica sfavorevoleCitogenetica sfavorevole

Linee terapia precedenteLinee terapia precedente

Precedente Precedente thalidomidethalidomide

Precedente bortezomibPrecedente bortezomib

Precedente trapiantoPrecedente trapianto

My-VTDMy-VTD

(42 (42 ptspts))

63 (35-81)63 (35-81)

32 (76)32 (76)

4 (9.5)4 (9.5)

nana

33 (1-6) (1-6)

27 27 (64)(64)

6 (14)6 (14)

10 10 (24)(24)

ThaDD-VThaDD-V(44 (44 ptspts))

868677774545

30305454

44 44 6363

OutcomesOutcomes

≥≥ PR PR≥≥ VGPR VGPR ≥≥ nCRnCR

Follow-upFollow-up mediano (mesi) mediano (mesi)2-yrs TTP (%)2-yrs TTP (%)2-yrs PFS (%)2-yrs PFS (%)2-yrs OS (%)2-yrs OS (%)

My-VTDMy-VTD(42 (42 ptspts))

7373nana5252

1818303020206666

ThaDD-VThaDD-V vsvs My-VTDMy-VTD: : outcomesoutcomes

ThaDD-VThaDD-V vsvs My-VTDMy-VTD: : medianmedian PFS PFS

PFS=28 mesi

ThaDD-VThaDD-V My-VTDMy-VTD

PFS=15 mesi

ThaDD-VThaDD-V vsvs My-VTDMy-VTD: eventi avversi grado 3-4: eventi avversi grado 3-4

Eventi avversiEventi avversi

NeutropeniaNeutropeniaPiastrinopeniaPiastrinopeniaInfezioniInfezioniAlopeciaAlopeciaEmorragiaEmorragiaTVPTVPNeuropatiaNeuropatiaPPEPPEEventi cardiaciEventi cardiaci

Totale eventiTotale eventi

ThaDD-VThaDD-V(44 (44 ptspts))

4 (9)4 (9)7 (16)7 (16)7 (15)7 (15)

0000

2 (4.5) 2 (4.5) 5 (11)5 (11)

0000

2525

My-VTDMy-VTD(42 (42 ptspts))

10 (24)10 (24)12 (29)12 (29)5 (12)*5 (12)*7 (17)7 (17)2 (5)2 (5)1 (2)1 (2)1 (2)1 (2)

0000

3838

* 10 (24%) grado 2 e 2 (5%) grado 3 episodi di neutropenia febbrile

CaelyxCaelyx quartaquarta novitànovità nelnel MM MM

ElevatiElevati livellilivelli didi risposterisposte didi ottimaottima qualitàqualità

CaelyxCaelyx determinadetermina unauna modestamodesta tossicitàtossicità ematologica ematologica

TossicitàTossicità extraematologicaextraematologica contenutacontenuta e e gestibilegestibile

OttimoOttimo comparatorecomparatore per per ulterioriulteriori studistudi didi fasefase III III

MyocetMyocet ancoraancora dada studiarestudiare

Considerazioni finaliConsiderazioni finali