ruolo dellautotrapianto nellera dellimmunoterapia con anticorpi monoclonali nei linfomi diffusi a...
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Ruolo dell’autotrapianto nell’era dell’immunoterapia con anticorpi
monoclonali nei Linfomi Diffusi a grandi cellule B.
MEDITERRANEAN SCHOOL OF ONCOLOGYMEDITERRANEAN SCHOOL OF ONCOLOGY Diagnostic and therapeutic burning questions on Diagnostic and therapeutic burning questions on
lymphoproliferative diseaseslymphoproliferative diseasesRieti 27-29 Ottobre 2006Rieti 27-29 Ottobre 2006
Umberto VitoloUmberto VitoloSSCVD Chemioimmunoterapia dei disordini SSCVD Chemioimmunoterapia dei disordini
LinfoproliferativiLinfoproliferativiDipartimento di OncoematologiaDipartimento di Oncoematologia
ASO San Giovanni Battista TorinoASO San Giovanni Battista Torino
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Treatment of Diffuse Large B Lymphomas
Young
high-risk
Young
high-risk
Young
low-risk
Young
low-risk
ElderlyElderly
IPI 0,1
IPI 2,3
≤60 years >60
years
R-CHOPR-CHOP
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Group Factors
2y OS 5y-OS
IPI (Shipp1993)
Low 0-1 79% 83%
Low-int 2 66% 69%
High-int 3 59% 46%
High 4-5 58% 32%
R-IPI Factors
2y-OS 4y-OS
Very-good 0 92% 92%
Good 1-2 86% 86%
Poor 3-5 56% 58%
Revised International Prognostic Factors (R-IPI) vs
Standard IPI ( Sehn et al 2005)
Sehn et al ASH 2005
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HDC and ASCT is effective in chemosensitive HDC and ASCT is effective in chemosensitive relapsed indolent and aggressive lymphomasrelapsed indolent and aggressive lymphomas
109 relapsed
DLCL patients
Philip T et al. NEJM 1995
OSOS
EFSEFS
OSOS
EFSEFS
Schouten HC. JCO, 2003
140 relapsed Follicular Lymhoma patients
Random
CHOP x 3
CHOP x 3
HDC + ASCT
DHAP x 4Random
DHAP x 2 + BEAC – ASCT
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HDC and ASCT may be effective as first line HDC and ASCT may be effective as first line treatment in indolent and aggressive lymphomastreatment in indolent and aggressive lymphomas
Event-free survival Event-free survival DLCL IPI 1-2DLCL IPI 1-2
Event-free survivalEvent-free survivalDLCL IPI 2-3DLCL IPI 2-3
GOELAMS GOELAMS study study
Milpied et al Milpied et al NEJM 2004 NEJM 2004
Intergruppo Intergruppo Italiano Linfomi Italiano Linfomi
studystudyVitolo et al Vitolo et al
Haematologica Haematologica 2005 2005
Gianni et Gianni et al, NEJM al, NEJM
1997 1997
Martelli et al. J Clin
Oncol 2003
EFS DLCLEFS DLCL
Event-free survivalEvent-free survivalDLCL IPI 2-3DLCL IPI 2-3
P = 0.2P = 0.2
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Cochrane Meta-analysis of the HR for OS for Cochrane Meta-analysis of the HR for OS for patients receiving conventional or HDC with ASCT: patients receiving conventional or HDC with ASCT:
14 randomized studies 14 randomized studies
Rodriguez 2003
Study
Total (95% CI)
Gianni Milpied Intragumtornchai Martelli 1996 Santini 1998 De Souza Haioun Martelli 2003 Kaiser Kluin-Nelemans
Verdonck Vitolo Gisselbrecht
Hazard Ratio (fixed) 95% CI
0.52 [0.24, 1.11]0.64 [0.40, 1.05]0.64 [0.30, 1.36]0.69 [0.29, 1.65]0.81 [0.48, 1.37]0.92 [0.45, 1.89]0.96 [0.71, 1.30]1.01 [0.59, 1.73]0.08 [0.75, 1.55]1.33 [0.75, 2.37]1.34 [0.68, 2.65]1.40 [0.73, 2.67]1.41 [0.82, 2.41]1.45 [1.08, 1.93]
1.05 [0.92, 1.19]
Hazard Ratio (fixed) 95% CI
0.1 0.2 0.5 1 2 5 10 Favours HDCT Favours control
Overall Survival
Engert A et al. Submitted to J Clin
Oncol 2006
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• Possible explanations for relapse Possible explanations for relapse – contamination of stem cell product contamination of stem cell product – residual tumour cells remaining after high-residual tumour cells remaining after high-
dose chemotherapy (HDT)dose chemotherapy (HDT)
• Improving outcomes in ASCTImproving outcomes in ASCT– in vivoin vivo purging agent purging agent– improving response rate before improving response rate before
transplantationtransplantation– post-transplant maintenance post-transplant maintenance
immunotherapyimmunotherapy
BUT . . . 40–55% of patients BUT . . . 40–55% of patients relapse after ASCTrelapse after ASCT
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Rituximab improves efficacy of standard chemotherapy in Rituximab improves efficacy of standard chemotherapy in indolent and aggressive lymphomasindolent and aggressive lymphomas
R-CVP: median 32 m
CVP: median 15 m
321 pts:321 pts: R-CVP x 8 R-CVP x 8 vs CVP x 8vs CVP x 8
Marcus et al: Marcus et al: Blood 2005Blood 2005
428 pts: 428 pts: R-CHOP x R-CHOP x
6-8 vs 6-8 vs CHOP x 6-8CHOP x 6-8Hiddemann Hiddemann et al: Blood et al: Blood
20052005
R-CHOP
CHOP
EFS FLEFS FL
EFS FLEFS FL
EFS DLBCL EFS DLBCL elderlyelderly
399 pts:399 pts: R-CHOP x 8 R-CHOP x 8 vs CHOP x 8vs CHOP x 8Feugier et al: Feugier et al:
JCO 2005JCO 2005
823 pts:823 pts: R-CHOP x 6 vs R-CHOP x 6 vs
CHOP x 6CHOP x 6Pfreundschuh et
al : ASH 2004: ASH 2004EFS DLBCL EFS DLBCL
young IPI 0-1young IPI 0-1
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R-CHOPR-CHOP
CHOP + RITUXIMAB is always the best treatment?CHOP + RITUXIMAB is always the best treatment?HDC with Rituximab + ASCT may improve the outcome of the patients?HDC with Rituximab + ASCT may improve the outcome of the patients?
Poor Prognosis DLBCL (IPI2-3)Poor Prognosis DLBCL (IPI2-3)
Refractory/early relapsed patientsRefractory/early relapsed patients
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High Dose Chemotherapy with Rituximab High Dose Chemotherapy with Rituximab and ASCT: Key issuesand ASCT: Key issues
Reducing lymphoma cell Reducing lymphoma cell contamination in PBSCcontamination in PBSC
Increasing outcome in Increasing outcome in IPI2-3 DLBCLIPI2-3 DLBCL
Dose of RituximabDose of Rituximab
Toxicity and delayed Toxicity and delayed engraftment after ASCTengraftment after ASCT
as in vivo purgingas in vivo purging
PossiblePossible
Standard or High doseStandard or High dose
PerhapsPerhaps
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A P O
G - C S FG - C S F
CTX7 g/sqm
1st PBPC1st PBPCharvestharvest
HD-ARAC
G - C S FG - C S F
2nd PBPCharvest 1s
t P
BP
Cau
tog
raft
2nd
PB
PC
auto
gra
ft
Rituximab
Modified HDS with Rituximab (R-HDS)Modified HDS with Rituximab (R-HDS)given prior to PBC collections for MCL given prior to PBC collections for MCL
Gianni AM et al. Blood 2003; 102 (2): 749-755
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Rituximab and HDC as in vivo purging in Rituximab and HDC as in vivo purging in PBSC harvestPBSC harvest
Gianni AM et al. Blood 2003; 102 (2): 749-755
28 MCL patients28 MCL patients
93%93%57%57%
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High Dose Chemotherapy with Rituximab High Dose Chemotherapy with Rituximab and ASCT: Key issuesand ASCT: Key issues
Reducing lymphoma cell Reducing lymphoma cell contamination in PBSCcontamination in PBSC
Increasing outcome in Increasing outcome in IPI2-3 DLBCLIPI2-3 DLBCL
Dose of RituximabDose of Rituximab
Toxicity and delayed Toxicity and delayed engraftment after ASCTengraftment after ASCT
as in vivo purgingas in vivo purging
PossiblePossible
Standard or High doseStandard or High dose
PerhapsPerhaps
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R-ICER-ICE ICEICE pp R-ICER-ICE ICEICE pp
Paz totaliPaz totali 7878 7171 0.530.53 5353 2727 0.010.01
RecidiveRecidive 9696 7979 0.070.07 6565 3434 0.010.01
RefrattariRefrattari 4646 6363 0.360.36 3131 1919 0.460.46
aaIPI L/LIaaIPI L/LI 7979 8686 0.470.47 5353 3939 0.420.42
aaIPI HI/HaaIPI HI/H 7676 6161 0.280.28 5353 1919 0.010.01
ORR%ORR% CR %CR %
Kewalramani T et al. Blood 2004; 103 (10): 3684-88
R-ICE + ASCT: aumento risposta pre-ASCTR-ICE + ASCT: aumento risposta pre-ASCTII linea in pz con B-DLCL in recidiva o refrattariII linea in pz con B-DLCL in recidiva o refrattari
R-ICE vs ICE: confronto storicoR-ICE vs ICE: confronto storico
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Kewalramani T et al. Blood 2004; 103 (10): 3684-88
Preautografting treatment with RituximabPreautografting treatment with Rituximab in relapsed aggressive Lymhomaa: in relapsed aggressive Lymhomaa:
R-ICE + ASCT vs ICE+ASCTR-ICE + ASCT vs ICE+ASCT
Rituximab IfosfamideCarboplatinoEtoposide
BEAM + ASCT
x 3 courses
PBSC
OSOS
36 pts R-ICE36 pts R-ICE147 pts ICE147 pts ICE
PFSPFS
R-ICE 78 patients
ICE 71 patients
CR 53%
p = .01
CR 27%
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A non randomized comparison between two groups of patients A non randomized comparison between two groups of patients enrolled into two consecutive phase II trial with up-front HDC and enrolled into two consecutive phase II trial with up-front HDC and ASCT with or without Rituximab with identical inclusion criteria: ASCT with or without Rituximab with identical inclusion criteria:
stage III/IV, IPI 2-3, < 60 yrs, EF > 45%stage III/IV, IPI 2-3, < 60 yrs, EF > 45%
Study Group R-HDCStudy Group R-HDC January 2001-December 2004January 2001-December 2004
77 pts77 pts
Control Group HDCControl Group HDC August 1991-August 1995August 1991-August 1995
41 pts41 pts
118 pts118 pts
Vitolo U, Cabras MG, Rossi G, Liberati M et al ASH 2006
R-HDC+ASCT as firts line therapy in poor R-HDC+ASCT as firts line therapy in poor prognosis (IPI 2-3) DLBCL, age 18-60prognosis (IPI 2-3) DLBCL, age 18-60
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Induction chemotherapy
Months 1 and 2
Intensified chemotherapy MAD (HD-ARAC +
Mitoxantrone x 3 days) Months 3 and 4
High dose chemotherapy BEAM + ASCT
Month 5
R
MegaCEOP14 x 4
R R
MAD MAD BEAM
R R
PBSC
ASCT
months
RR--HHDDCC
R = Rituximab
R
0 1 2 3 4 5
R-MEGACEOP14
R 375 mg/m2 d 1Epi 110 mg/m2 d 3 Ctx 1200 mg/m2 d 3 Vcr 1.4 mg/m2 d 3 Pdn 40 mg/m2 dd 1 5 G-CSF 5 mcg/kg dd 5 12
R-MAD
Mito 8 mg/m2 dd 1 3 ARA-C 2 g/m2/12h dd 1 3 Dex 4 mg/m2/12h dd 1 3R 375 mg/m2 d 4 and d -1PBSCG-CSF 5 µg/Kg d 4
months
HHDDCC
0 1 2 3 4 5
MACOPB x 8 weeks MAD MAD BEAMPBSC
ASCT
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3-yrs OS3-yrs OS
54% HDC54% HDC
80% R-HDC80% R-HDC
p = .004p = .004
3-yrs FFS3-yrs FFS
64% R-HDC64% R-HDC
46% HDC46% HDC
p = .016p = .016
3-yr Failure-free and overall survival3-yr Failure-free and overall survival
Median Follow-up time: R-HDC 36 months; HDC 72 months
Vitolo et al ASH 2005
R-HDC 77 patients
HDC 41 patients
CR 78%
CR 68%
NO ASCT: 17 (22%)
NO ASCT: 10 (24%)p = .25
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Haioun C. et al, ASH 2005 abs 677Haioun C. et al, ASH 2005 abs 677
Maintenance Rituximab after HDC in poor Maintenance Rituximab after HDC in poor risk DLBCL: LNH98-B3 GELA Studyrisk DLBCL: LNH98-B3 GELA Study
Ran
do
mR
and
om
ACVBPACVBP
HDC HDC
(ACE)(ACE)
Ran
do
mR
and
om
Maintenance Maintenance RituximabRituximab
ObservationObservation
3-yrs EFS maintenance vs observation: 80% vs 72% p=.10 3-yrs EFS maintenance vs observation: 80% vs 72% p=.10 3-yrs EFS maintenance vs observation: 80% vs 72% p=.10 3-yrs EFS maintenance vs observation: 80% vs 72% p=.10
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High Dose Chemotherapy with Rituximab High Dose Chemotherapy with Rituximab and ASCT: Key issuesand ASCT: Key issues
Reducing lymphoma cell Reducing lymphoma cell contamination in PBSCcontamination in PBSC
Increasing outcome in FL, Increasing outcome in FL, MCL, IPI2-3 DLBCLMCL, IPI2-3 DLBCL
Dose of RituximabDose of Rituximab
Toxicity and delayed Toxicity and delayed engraftment after ASCTengraftment after ASCT
as in vivo purgingas in vivo purging
PossiblePossible
Standard or High doseStandard or High dose
PerhapsPerhaps
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Khoury IF et al. J.Clin.Oncol. 2005; 23: 2240-47Khoury IF et al. J.Clin.Oncol. 2005; 23: 2240-47
High or standard dose of Rituximab with High or standard dose of Rituximab with ASCT?ASCT?
Day + 7Day + 7Rituximab Rituximab 1000 mg/mq1000 mg/mq
Day – 1Day – 1RituximabRituximab
375 mg/mq375 mg/mq
Edx OREdx ORIfo+VP16Ifo+VP16
G-CSF 10 mcg/kgG-CSF 10 mcg/kgGM-CSF 250 GM-CSF 250 mcg/mqmcg/mq
HARVEST
BEAMBEAM
Day 0 Day 0 ASCTASCT
Day + 1 and + 8Day + 1 and + 8Rituximab Rituximab
1000 mg/mq1000 mg/mqDay 0Day 0GM-CSF 250 GM-CSF 250 mcg/mqmcg/mq
OSOS DFSDFS
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High Dose Chemotherapy with Rituximab High Dose Chemotherapy with Rituximab and ASCT: Key issuesand ASCT: Key issues
Reducing lymphoma cell Reducing lymphoma cell contamination in PBSCcontamination in PBSC
Increasing outcome in FL, Increasing outcome in FL, MCL, IPI2-3 DLBCLMCL, IPI2-3 DLBCL
Dose of RituximabDose of Rituximab
Toxicity and delayed Toxicity and delayed engraftment after ASCTengraftment after ASCT
as in vivo purgingas in vivo purging
PossiblePossible
Standard or High doseStandard or High dose
PerhapsPerhaps
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Engraftment impairment in patients Engraftment impairment in patients treated with Rituximab?treated with Rituximab?
Hoerr AL et al. J.Clin.Oncol. 2004
P < .04
P < .01
Benekli M et al. B. Marrow Transpl. 2003
Platelets engraftmentPlatelets engraftmentR vs no-R: 39 (33-46) vs 27 (22-29)R vs no-R: 39 (33-46) vs 27 (22-29)
Neutrophils engraftmentNeutrophils engraftmentR vs no-R: 13 (9-28) vs 12 (8-28)R vs no-R: 13 (9-28) vs 12 (8-28)
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Post-tranplantation toxicity in patients treated Post-tranplantation toxicity in patients treated with preautografting Rituximabwith preautografting Rituximab
Infections/Infections/
feverfever
R vs No-RR vs No-R
BacteremiaBacteremia
R vs No-RR vs No-R
N° patientsN° patients
Benekli et al Benekli et al BMT 2003BMT 2003
69% vs 44%69% vs 44% 62% vs 26%62% vs 26% 4747
Hoerr et al JCO Hoerr et al JCO 20042004
76% vs 81%76% vs 81% 25% vs 22% 25% vs 22% 273273
Khouri et al Khouri et al JCO 2005JCO 2005
37% vs 47%37% vs 47% NANA 9797
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Rituximab as adjuvant to HDT and ASCT for aggressive lymphoma: delayed B cell ricovery
Horwitz SM et al. Blood 2004
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Do we need to stay on CHOP + RITUXIMAB or Do we need to stay on CHOP + RITUXIMAB or explore new treatments in aggressive explore new treatments in aggressive
lymphomas?lymphomas?
R-CHOPR-CHOP
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DSHNHL trial < 60yrs aa-IPI 2-3
R-MegaCHOEP x 4 vs R-CHOEP14 x 8
GOELAMS trial < 60yrs aa-IPI 2-3R-CHOP14 x 8 vs R-CEEP15 + HD-ARAC/MTX + BEAM-ASCT
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Phase III randomized, multicenter study in poor-prognosis Phase III randomized, multicenter study in poor-prognosis (IPI2-3) DLBCL young patients.(IPI2-3) DLBCL young patients.
Dose-dense chemotherapy + Rituximab +/- intensified and Dose-dense chemotherapy + Rituximab +/- intensified and high dose chemoimmunotherapy with ASCT.high dose chemoimmunotherapy with ASCT.
Umberto Vitolo (Torino), Emanuele Angelucci (Cagliari), Monica Balzarotti (Rozzano), Ercole Brusamolino (Pavia), Nicola Di Renzo (Lecce), Maurizio Martelli (Roma), Luigi Rigacci (Firenze), Gino Santini (Genova)
Study ID: IIL-DLCL04Study ID: IIL-DLCL04
Comitato di stesura:
Revisione Istologica e studi biologici:
ResponsabileStefano Pileri
(Bologna)
Disegno statistico e analisi dati:
ResponsabileGianni Ciccone
(Torino)
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B-DLCL giovani (18-60) IPI 2-3
RC/RP
RC/RP
RC/RP
RC/RP
NR
Off study
R-MegaCHOP14 x 4 R-MAD x 2BEAM+ASCT
NR
Off study
RRAANNDDOOMMIIZZAATTIIOONN
R-CHOP14 x 4
R-CHOP14 x 4
R-MegaCHOP14x 2
R-CHOP14x 4
RR
EE
SS
TT
AA
GG
II
NN
GG
R-MegaCHOP14 x 4
R-MAD x 2BEAM+ASCT
188 PZ
188 PZ
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CRITERI DI INCLUSIONECRITERI DI INCLUSIONE
PS < 3 se non dovuto al linfoma PS < 3 se non dovuto al linfoma Frazione di eiezione cardiaca > 45% Frazione di eiezione cardiaca > 45% Normale funzionalità epatica, renale, polmonareNormale funzionalità epatica, renale, polmonare Markers virali HIV, HBV e HCV negativiMarkers virali HIV, HBV e HCV negativi HCV+ senza segni di replicazione in atto confermata istologicamenteHCV+ senza segni di replicazione in atto confermata istologicamente AntiHBc+, HbsAg-, AntiHBs+/- (portatori occulti) AntiHBc+, HbsAg-, AntiHBs+/- (portatori occulti) Aspettativa di vita > 3 mesiAspettativa di vita > 3 mesi Assenza di gravidanza in atto al momento dell’inizio della chemioterapiaAssenza di gravidanza in atto al momento dell’inizio della chemioterapia Consenso informato scrittoConsenso informato scritto
Età 18-60Età 18-60
Istologia: Linfoma diffuso a grandi cellule B CD 20 + (de novo o shift Istologia: Linfoma diffuso a grandi cellule B CD 20 + (de novo o shift da NHL a basso grado se non pretrattati), Linfoma follicolare grado 3bda NHL a basso grado se non pretrattati), Linfoma follicolare grado 3b
Age-adjusted IPI 2 o 3 (intermedio-alto o alto rischio)Age-adjusted IPI 2 o 3 (intermedio-alto o alto rischio)
Stadio II avanzato, III, IV con almeno 2 fattori di rischio sec. aa-IPIStadio II avanzato, III, IV con almeno 2 fattori di rischio sec. aa-IPI
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R
MC MC
R
MC
R
MC MAD MAD BEAM
R RPBSC
ASCT
R
0 +14 +28 +42 +70 +98 +126
RESTAGING
R
C C
R
C
R
C MAD MAD BEAM
R RPBSC
ASCT
R
0 +14 +28 +42 +70 +98 +126
RESTAGING
R
MC MC
R
MC
R
MC
R RR
0 +14 +28 +42 +56
RESTAGING
+70
MC MC
R
C C
R
C
R
C
R RR
0 +14 +28 +42 +56
RESTAGING
+70
C C
R R
C C
+86 +100
Schema 1: Schema 1: R= RituximabR= RituximabMC = MegaCHOP14MC = MegaCHOP14
Schema 1 bis: Schema 1 bis: R= RituximabR= RituximabC = CHOP14C = CHOP14
Schema 2: Schema 2: R= RituximabR= RituximabMC = MegaCHOP14MC = MegaCHOP14
Schema 2 bis: Schema 2 bis: R= RituximabR= RituximabC = CHOP14C = CHOP14
R-MegaCHOP14R-MegaCHOP14
Rituximab* 375 mg/mRituximab* 375 mg/m22 g 1 g 1Ciclofosfamide 1200 mg/mCiclofosfamide 1200 mg/m22 g 1 g 1 Doxorubicina 75 mg/mDoxorubicina 75 mg/m22 g 1 g 1Vincristina 1,4 mg/mVincristina 1,4 mg/m22 (max 2 mg) g 1 (max 2 mg) g 1Prednisone 100 mg gg 1-5Prednisone 100 mg gg 1-5Pegfilgrastim 6 mg 24 ore dopo la Pegfilgrastim 6 mg 24 ore dopo la chemioterapia in unica somministrazionechemioterapia in unica somministrazione*Rituximab g 8 nel ciclo 1*Rituximab g 8 nel ciclo 1
R-MADR-MAD
Mitoxantrone 8 mg/mMitoxantrone 8 mg/m22/die gg 1-3/die gg 1-3ARA-C 2000 mg/mARA-C 2000 mg/m22/12 h gg 1-3/12 h gg 1-3Desametazone 4 mg/mDesametazone 4 mg/m22/12 h gg 1-3/12 h gg 1-3Rituximab* 375 mg/mRituximab* 375 mg/m22 g 4 e prima di g 4 e prima di raccolta PBSCraccolta PBSCLenograstim 5 µg/Kg/die a partire da 48 h Lenograstim 5 µg/Kg/die a partire da 48 h dopo la chemioterapia e fino a raccolta di dopo la chemioterapia e fino a raccolta di PBSC (tra il giorno +13 e +15)PBSC (tra il giorno +13 e +15)*solo nel I ciclo R-MAD*solo nel I ciclo R-MAD
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Revisione istologica centralizzata e caratterizzazione immunoistochimica Revisione istologica centralizzata e caratterizzazione immunoistochimica del profilo di espressione genica (Germinal Center Cell e non-Germinal del profilo di espressione genica (Germinal Center Cell e non-Germinal Center Cell) in tutti i pazienti arruolati nello studio. Center Cell) in tutti i pazienti arruolati nello studio. Per tale revisione i centri dovranno inviare entro 30 giorni dalla Per tale revisione i centri dovranno inviare entro 30 giorni dalla diagnosi il materiale diagnostico (blocchetto in paraffina) al patologo diagnosi il materiale diagnostico (blocchetto in paraffina) al patologo di riferimento.di riferimento.
Revisione Istologica centralizzata e studi biologiciRevisione Istologica centralizzata e studi biologici
Responsabile: Responsabile: Stefano Pileri (Bologna)Stefano Pileri (Bologna)
Antonino Carbone (Aviano)Antonino Carbone (Aviano)Simonetta Di Lollo (Firenze)Simonetta Di Lollo (Firenze)Fabio Facchetti (Brescia)Fabio Facchetti (Brescia)Brunagelo Falini (Perugia)Brunagelo Falini (Perugia)Vito Franco (Palermo)Vito Franco (Palermo)Marcello Gambarotta (Milano)Marcello Gambarotta (Milano)Lorenzo Leoncini (Siena)Lorenzo Leoncini (Siena)Domenico Novero (Torino) Domenico Novero (Torino) Marco Paulli (Pavia)Marco Paulli (Pavia)Edorado Pescarmona (Roma)Edorado Pescarmona (Roma)Mauro Truini (Genova)Mauro Truini (Genova)Alessandro Vitali (Genova)Alessandro Vitali (Genova)
Abbonamento dedicatoAbbonamento dedicatoDHL 105310796DHL 105310796
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IIL-DLCL04 IIL-DLCL04 Participating Italian Centers: 79Participating Italian Centers: 79Planned sample size: 376 patientsPlanned sample size: 376 patients
Piemonte 11
Liguria 3
Lombardia 14
Veneto 4
Friuli 2
Emilia Romagna 10
Toscana 3Marche 1
Umbria 2Abruzzo 1
Molise 1Lazio 7
Sardegna 2
Sicilia 2Calabria 4
Basilicata 2
Campania 5 Puglia 5
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STATO ARRUOLAMENTO SETTEMBRE 2006STATO ARRUOLAMENTO SETTEMBRE 2006
PAZIENTI – aggiornamento Settembre 2006
TARGETARRUOLATI
TOTALE ARRUOLATI
RANDOMIZZATI
SCHEMA 1
SCHEMA 1 BIS
SCHEMA 2
SCHEMA 2 BIS
IPI 2 IPI 3DROP OUT
376 31 8 7 9 7 16 15 0
0
5
10
15
20
25
30
35
40
45
GEN
FEB
MAR
APR
MAG
GIU
LUG
AGO
SET
0TT
AttivazioneCentri
ArruolamentoPazienti
IIL-DLCL04:IIL-DLCL04:39/79 centri attivi39/79 centri attivi
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R-CHOP14R-CHOP14 R-HDCR-HDC
DLBCLDLBCLcurecure
IIL-DLCL04IIL-DLCL04
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ConclusionsConclusionsAddition of Rituximab to HDCAddition of Rituximab to HDC
It is feasible without additional acute toxicity.It is feasible without additional acute toxicity.
It allows to collect lymphoma-free PBSC.It allows to collect lymphoma-free PBSC.
The empairment of engraftment, if any, is not clinically The empairment of engraftment, if any, is not clinically relevant.relevant.
Preliminary results in DLBCL are encouraging.Preliminary results in DLBCL are encouraging.
Many schedules have been used so far: pre ASCT Many schedules have been used so far: pre ASCT chemotherapy, immediately before and after ASCT, maintenance chemotherapy, immediately before and after ASCT, maintenance prevent definite conclusions prevent definite conclusions
Immune reconstitution and late toxicities after ASCT need to be Immune reconstitution and late toxicities after ASCT need to be monitored and properly studiedmonitored and properly studied
Randomized studies are ongoing to compare the efficacy of R-Randomized studies are ongoing to compare the efficacy of R-HDC vs R-CHOP.HDC vs R-CHOP.
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G. Benevolo B. Botto A. Chiappella L. Orsucci P. Pregno
ANATOMIA PATOLOGICAANATOMIA PATOLOGICAUniversità TorinoUniversità Torino Prof G. Inghirami Prof G. Inghirami
P. Francia di Celle L. Godio D. Novero A.Stacchini
RingraziamentiRingraziamenti
EPIDEMIOLOGIA DEI TUMORIEPIDEMIOLOGIA DEI TUMORIUniversità di TorinoUniversità di Torino
Prof F. MerlettiProf F. Merletti
G. Ciccone M. Ceccarelli F. Saccona
SSCVD Chemioimmunoterapia SSCVD Chemioimmunoterapia dei Linfomidei Linfomi
EMATOLOGIA EMATOLOGIA ASO S.Giovanni Torino ASO S.Giovanni Torino