ruolo dellautotrapianto nellera dellimmunoterapia con anticorpi monoclonali nei linfomi diffusi a...

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

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

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

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

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

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

• 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

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

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

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

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

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%



Increasing outcome in Increasing outcome in IPI2-3 DLBCLIPI2-3 DLBCL




PossiblePossible


PerhapsPerhaps

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

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%

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

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

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

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



Increasing outcome in FL, Increasing outcome in FL, MCL, IPI2-3 DLBCLMCL, IPI2-3 DLBCL




PossiblePossible


PerhapsPerhaps

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



Increasing outcome in FL, Increasing outcome in FL, MCL, IPI2-3 DLBCLMCL, IPI2-3 DLBCL




PossiblePossible


PerhapsPerhaps

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)

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

Rituximab as adjuvant to HDT and ASCT for aggressive lymphoma: delayed B cell ricovery

Horwitz SM et al. Blood 2004

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

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

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)

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

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

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

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

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

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

R-CHOP14R-CHOP14 R-HDCR-HDC

DLBCLDLBCLcurecure

IIL-DLCL04IIL-DLCL04

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.

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

ruolo dellautotrapianto nellera dellimmunoterapia con anticorpi monoclonali nei linfomi diffusi a...

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