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