rituximab in aggressive nhl: why combination therapy should not be delayed
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Rituximab in aggressive NHL: why combination therapy should not be
delayed
Bertrand Coiffier
Pathologie des Cellules LymphoïdesEA 3737 – Université Claude Bernard
Groupe d’Étude des Lymphomes de l’Adulte
Service d’HématologieHospices Civils de Lyon
The benefits of monoclonal antibodies
Combining rituximab and chemotherapy– increases CR rates – prolongs survival
Rituximab plus CHOP (R-CHOP) is the gold standard
No sufficient data for other antibodies
CHOP = cyclophosphamide, doxorubicin, vincristine, predrisoneCR = complete response
Major randomised studies
R-CHOP as the standard
DLBCLAge 60–80 yearsNo prior treatment PS 0–2 Stage II–IV
RANDOMISATION
LNH 98.5 study: design
CHOP every
3 weeks x 8
R-CHOPevery
3 weeks x 8
Coiffier B, et al. N Engl J Med 2002;346:235
Rituximab: 375mg/m2 on day 1Cyclophosphamide: 750mg/m2 on day 1Doxorubicin: 50mg/m2 on day 1Vincristine: 1.4mg/m2 (up to 2mg/m2) on day 1Prednisolone: 40mg/m2/day days 1–5
Rituximab: 375mg/m2 on day 1Cyclophosphamide: 750mg/m2 on day 1Doxorubicin: 50mg/m2 on day 1Vincristine: 1.4mg/m2 (up to 2mg/m2) on day 1Prednisolone: 40mg/m2/day days 1–5
DLBCL = diffuse large B-cell lymphomaPS = performance status
LNH 98.5 study: treatment responses
p=0.005
Coiffier B, et al. N Engl J Med 2002;346:235PR = partial response
6
31
63
CHOP (n=197)
CR PR No response
718
75
R-CHOP (n=202)
Median follow-up 7 yearsPFS
OS
Coiffier B, et al. J Clin Oncol2007;25(Suppl. 18):443s (Abstract 8009)
EFS = event-free survival; PFS = progression-free survivalDFS = disease-free survival; OS = overall survival
EFS1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity CHOP
R-CHOP
p<0.0001
0 1 2 3 4 5 6 7 8 9
DFS1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity
CHOPR-CHOP
p=0.0001
CHOPR-CHOP
1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity
1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity
Years
CHOPR-CHOP
p<0.0001
p=0.0004
0 1 2 3 4 5 6 7 8 9Years
0 1 2 3 4 5 6 7 8 9Years
0 1 2 3 4 5 6 7 8 9Years
Results according to aaIPIPFS: high risk
OS: high risk
PFS: low risk
OS: low risk
aaIPI = age adjusted International Prognostic Index
1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity
CHOPR-CHOP
1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity
1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity
1.0
0.8
0.6
0.4
0.2
0Su
rviv
al p
rob
abil
ity
CHOPR-CHOP
CHOPR-CHOP
CHOPR-CHOP
p=0.0051
p=0.0030
p=0.0022
p=0.0213
0 1 2 3 4 5 6 7 8 9Years
0 1 2 3 4 5 6 7 8 9Years
0 1 2 3 4 5 6 7 8 9Years
0 1 2 3 4 5 6 7 8 9Years
Coiffier B, et al. J Clin Oncol2007;25(Suppl. 18):443s (Abstract 8009)
p=0.000000007
R-chemotherapy
Chemotherapy
1.0
0.8
0.6
0.4
0.2
0
Months
Pro
ba
bil
ity
MInT study1
TT
F
Years0 1 2 3 4 5
ECOG study3
Maintenance
ObservationCHOPR-CHOP
R-CHOP-14
p=0.000025
FF
S
0 5 10 15 20 25 30 35 40 45Months
RiCOVER study4
CHOP-14
British Columbia2
Years
Su
rviv
al Post-rituximab
Pre-rituximab
p=0.0001
1Pfreundschuh M, et al. Lancet Oncol 2006;7:379–912Sehn LH, et al. J Clin Oncol 2005;23:5027–33
3Habermann T, et al. J Clin Oncol 2006;24:3121–74Pfreundschuh M, et al. Lancet Oncol 2008;Jan 14:Epub ahead of print
MInT = MabThera International TrialECOG = Eastern Cooperative Oncology GroupTTF = time-to-treatment failureFFS = failure-free survival
R-CHOP: a consistent clinical benefit1.0
0.8
0.6
0.4
0.2
0
1.0
0.8
0.6
0.4
0.2
0
1.0
0.8
0.6
0.4
0.2
0
0 5 10 15 20 25 30 35 40 45 50 0 1 2 3 4
1.0
0.8
0.6
0.4
0.2
0
YearsFeugier P, et al. J Clin Oncol 2005 23:4117–26
Su
rviv
alGELA R-CHOP study
0 1 2 3 4 5 6
R-CHOP
CHOP
P=0.007
Standard CHOP Rituximab 375mg/m2
1 2 3 4 5 6 7 8
R R
No further treatment
Rituximabfour infusionsevery 6 monthsfor 2 years
SDPRCR
Intergroup study of CHOP or R-CHOP rituximab as maintenance therapy
Habermann T, et al. J Clin Oncol 2006;24:3121–7SD = stable disease
Induction therapy: TTFP
rob
abil
ity
HR=0.78p=0.04
R-CHOP ( rituximab maintenance)
CHOP ( maintenance)
1.0
0.8
0.6
0.4
0.2
0
Years from study entry
Habermann T, et al. J Clin Oncol 2006;24:3121–7Evaluable patients n=546
0 1 2 3 4 5
ECOG 4494: effect of rituximab maintenance on FFS according to induction regimen
Years
R-CHOP inductionCHOP induction
0 1 2 3 4 5
p=0.81
Rituximab maintenance
Observation
p=0.0004
Pro
bab
ility
1.0
0.8
0.6
0.4
0.2
0
Rituximab maintenance
Observation
Years
Pro
bab
ility
0 1 2 3 4 5
1.0
0.8
0.6
0.4
0.2
0
Habermann T, et al. J Clin Oncol 2006;24:3121–7
CD20+ DLBCL18–60 years
IPI 0, 1stages II–IV,I with bulk
6 x CHOP-like+ 30–40 Gy (Bulk, E)
6 x CHOP-like+ rituximab
+ 30–40 Gy (Bulk, E)
MInT: trial design
Pfreundschuh M, et al. Lancet Oncol 2006;7:379–91
CHOP-21 (n=396)CHOEP-21 (n=362)MACOP-B (n=33)PMitCEBO (n=32)
Randomisation
MInT studyEFSEFS PFSPFS OSOS
Pfreundschuh M, et al. Lancet Oncol 2006;7:379–91
N at risk
R-chemotherapy 413 296 256 156 37 0 Chemotherapy 410 229 194 101 28 1
EF
S (
%)
100
80
60
40
20
0
413 313 266 151 37 0 413 364 318 184 51 2
410 253 205 104 27 1 410 349 283 150 44 1
Months0 12 24 36 48 60
Months Months
PF
S (
%)
OS
(%
)
R-chemotherapy
Chemotherapy
Log-rank p<0.0001 Log-rank p<0.0001 Log-rank p=0.0001
100
80
60
40
20
0
100
80
60
40
20
00 12 24 36 48 60 0 12 24 36 48 60
Chemotherapy
Chemotherapy
R-chemotherapyR-chemotherapy
CD20+ DLBCL
stages I–IV
61–80 years
RiCOVER-60: trial design
6 x CHOP-14+ 36 Gy (Bulk, E)
8 x CHOP-14+ 36 Gy (Bulk, E)
6 x CHOP-14+ 36 Gy (Bulk, E)+ 8 x rituximab
8 x CHOP-14+ 36 Gy (Bulk, E)+ 8 x rituximab
Eight doses of rituximab regardless ofnumber of cycles of chemotherapy
Only 80% with DLBCL60% IPI 0–2All patients received a pre-phase
Only 80% with DLBCL60% IPI 0–2All patients received a pre-phase
Pfreundschuh M, et al. Blood 2006;108:64a (Abstract 205)Pfreundschuh M, et al. Lancet Oncol 2008. In press
Pfreundschuh M, et al. Blood 2006;108:64a (Abstract 205)Pfreundschuh M, et al. Lancet Oncol 2008. In press
Random2 x 2
factorialdesign
Months
1.0
0.8
0.6
0.4
0.2
0
Pro
po
rtio
n
0 10 20 30 40 50 60 70 80
6 x CHOP-14
8 x CHOP-14
6 x CHOP-14 + 8 x rituximab
8 x CHOP-14 + 8 x rituximab
RiCOVER-60
8 x CHOP-14
6 x CHOP-14
6 x CHOP-14 + 8 x rituximab
8 x CHOP-14 + 8 x rituximab
OSEFS
Pfreundschuh M, et al. Lancet Oncol 2008;Jan 14:Epub ahead of printPfreundschuh M, et al. Lancet Oncol 2008;Jan 14:Epub ahead of print
Months0 10 20 30 40 50 60 70 80
1.0
0.8
0.6
0.4
0.2
0
Pro
po
rtio
n
Questions
Question 1: R-CHOP-21 or R-CHOP-14?
R-CHOP-14 or -21?
No randomised study published
Tolerability is good but pre-phase and six cycles in German study
Other phases II seemed to find a poorer tolerability
Probability that R-CHOP-14 can be superior to R-CHOP-21 is low
Equivalent results if eight rituximab infusions
Prophylactic darbepoietin alfa
Supportive care
LNH 03-6B: 66–80 years, aaIPI = 1,2,3(R Delarue, A Bosly)
4 IT MTXR
R-CHOP-21
0 3 6 9 Weeks12 15 18 21
0 2 4 6 10 14 Weeks8 12
R-CHOP-14
Primary endpoint: EFS Expected improvement: 10% at 3 years with R-CHOP-14 (55–65%)600 patients required (4 years)IT = intrathecalMTX =methotrexate
Abstract 2436
Delarue R, et al.
Questions
Question 2: dose-dense/dose-intense regimens?
ConsolidationInduction
MTX 3g/m²
Ara-C 100mg/m²/day x 4 days
Doxorubicin 75mg/m² day 1Cyclophosphamide 1,200mg/m² day 1Vindesine 2mg/m² day 1, day 5Bleomycin 10mg day 1, day 5Prednisone 60mg/m² day 1–5IT MTX 15mg day 2G-CSF 5µg/kg day 6–13
ACVB plus sequential consolidation
ACVB = adriamycin, cyclophosphamide, vindesine, bleomycinG-CSF = granulocyte-colony stimulating factor; IFM = ifosfamide; MTX = methotrexate
Week
ACVB
ResponseResponse
0 2 4 6 10 12 14 16 18 20 22 26
MTX IFM 1,500mg/m²
VP16 300mg/m²
Ara-C
S.C.
I II III IV
Survival with ACVB in LNH regimens
Years
1.0
0.8
0.6
0.4
0.2
00 5 10 15 20
Su
rviv
al p
rob
abil
ity
NHL = non-Hodgkin’s lymphoma
LNH-80
LNH-84
LNH-87
LNH-93
ACVBP
CHOP
p=0.03
R0 3 6
60 3
9
12
13
15
17
18
19 21 23 25 27
9
15
21
ACVBP
CHOP
MTX IFM – VP16 Ara-C
Week
Week
ACVBP
CHOP
p=0.005
SurvivalDFS100
80
60
40
20
00 2 4 6 8 10
Years
Su
rviv
al (
%)
Year
Tilly H, et al. Blood 2003;102:4284–9
ACVBP regimen versus CHOP in advanced aggressive lymphoma
100
80
60
40
20
0
Su
rviv
al (
%)
0 2 4 6 8 10
ACVBP = adviamycin, cyclophosphamide, viudesine, bleomycin, prednisone
LNH 03-2B: <60 years, aaIPI = 1(C Recher, H Tilly)
R
60 3 12 15 189 21
R-ACVBP-14
R-CHOP-21Weeks
MTX
IFM – VP16
ARA-C
0 2 4 6 10 14 24 Weeks
4 x IT MTX
Primary endpoint = EFS Expected improvement: 10% at 2 years with R-ACVBP (75–85%)380 patients required (in 4 years)
Questions
Question 3: high-dose therapy and autotransplant?
SurvivalDFS
p=0.02 p=0.04
Induction phase ACVB four cycles CR
Sequential consolidation
MTX/IFM – VP16/L-Aspa/Ara-C
MTX/CBV + ABMT
RANDOMISATION
IPI 2–3: n=236
0 24 48 72 96 120 144Months
Su
rviv
al
(%)
100
80
60
40
20
0
Months
Su
rviv
al
(%)
ASCT = autologous stem cell transplantation; CBV = cytarabine, BCNU, etoposide; HDT = high-dose therapy
Benefit of HDT with ASCT in first CR
0 24 48 72 96 120 144
100
80
60
40
20
0
Interim PET scanning as a prognostic tool in DLBCL
Pretreatment Mid-treatment
PET = positron emission tomography
PET positive (n=32) 2 years EFS = 46%
PET negative (n=49) 2 years EFS = 80%
p=0.0003
Years
EFS according to PET status after two cycles
1.00
0.75
0.50
0.25
0 0 1 2 3 4 5
Pro
bab
ilit
y
LNH07-3B study: patients with aaIPI >2 and <61 years
2 x R-ACVBP-14
Sequential consolidation
Negative
2 x R-ACVBP-14
Positive Negative
Positive
Z-BEAM
SalvageCORAL study if biopsy
Negative
2 x R-CHOP-14
4 x R-CHOP-14
Negative
2 x R-CHOP14
Positive
Negative
Positive
Z-BEAM
SalvageCORAL study if biopsy
Negative
TEP C4TEP 0 TEP C2
R
Athens, February 2007Z-BEAM = 90Y ibritumomab, BCNU, ara-c, etoposide, melphalan
Questions
Question 4: which ways to improve these results?
Day of treatment
Ser
um
lev
els
(mg
/ml)
Courtesy of Reiser M, Cologne
Rituximab PK: trough serum levels200
180
160
140
120
100
80
60
40
20
0
R-CHOP-14
PK = pharmacokinetics
1 9 17 25 33 41 49 57 65 73 81 89 97 105 113
PK model based on median values of PK parameters for KELM, V1 (l/kgLBMc), K12, and K21 of 20 patients treated with R-CHOP-14 according to a two-compartment model. Model was then calculated for 21 days interval
PK model R-CHOP-14 versus R-CHOP-21
mg
/mL
300
225
150
75
0
R-CHOP-14R-CHOP-21
09.00
CHOP
CHOP
CHOP
CHOP
CHOP
CHOPDense-R-CHOP-14
(12 x R)
12 14
CHOP
CHOP
CHOP
CHOP
CHOP
CHOP
12 14
R-CHOP-14(8 x R)
Rituximab schedules for DLBCL
Rituximab PK: trough serum levels
Day of treatment
Ser
um
leve
l (m
g/m
L)
200
180
160
140
120
100
80
60
40
20
01 9 17 25 33 41 49 57 65 73 81 89 97 105 113
Dense-R-CHOP-14
R-CHOP-14
Dense-R-CHOP-14 (n=47)versus R-CHOP-14 (n=306)
Dense-R-CHOP-14: IPI=1–2Dense-R-CHOP-14: IPI=3–5R-CHOP-14: IPI=1–2R-CHOP-14: IPI=3-5
1.0
0.8
0.6
0.4
0.2
00 2 4 6 8 10 12
Months
Per
cen
tag
e
Potential applications of RIT in DLBCL
Is there a role for RIT rather than radiotherapy in localised disease?
Is there a role of RIT as ‘consolidation’ therapy to improve the quality of response?
What is the optimal way to incorporate RIT into R-CHOP regimens?
RIT = radioimmunotherapy
Can RIT improve the quality of response after R-CHOP in those failing to achieve CR?
Numerous mature phase II trials in follicular lymphoma showing improvements in quality of response (conversion from PR to CR 60–90%)
Single agent phase II data 90Y-ibritumomab demonstrating high response rate in chemotherapy refractory DLBCL
Emerging phase II data all confirm feasibility of integrating RIT with R-chemotherapy in DLBCL
RIT toxicity mainly haematological, predictable and manageable, otherwise non-overlapping
Studies combining chemotherapy and RIT for untreated DLBCL
Group Patients Study
SWOG Early stage; unfavorable CHOP (x3), IFXRT, 90Y-ibritumomab tiuxetan
ECOG Stage I–II disease R-CHOP (x2); if CR: CHOP (x2) + 90Y-ibritumomab tiuxetan; if PR: CHOP (x4), + 90Y-ibritumomab tiuxetan, IFXRT
SWOG >60 years; bulky II, III, IV R-CHOP (x6), CHOP (x2), 131I tositumomab
MSKCC >60 years, aaIPI 2 R-CHOP (x6), 90Y ibritumomab tiuxetan
European >60 years R-CHOP (x6), if CR: 90Y-ibritumomab tiuxetan versus observation; if PR: 90Y- ibritumomab tiuxetan
European >60 years R-CHOP (x2), 90Y-ibritumomab tiuxetan and repeat the sequence
IFXRT = involved-field external radiation therapy; MSKCC = Memorial Sloan-Kettering Cancer Center; SWOG = Southwest Oncology Group
New molecules?
New monoclonal antibodies– same antigen– different antigens: CD19, CD22, CD80– conjugated, toxine, isotope– bispecific antibodies
Bortezomib, revlimid
Bevacizumab
SAHA, HDACi
Questions
Question 5: at time of relapse
Relapse/refractory/PR
Relapse: PD after CR
PR: response but incomplete– presence of persisting lymphoma cells– tumour fixing with PET scan
Refractory: PD during treatment or just after the end of treatment
Highly different outcome
PD = progressive disease
Management of aggressive NHL
Induction chemotherapy
Responsive Primary refractory
Relapse
HDT with ASCT
Second-line therapy Second-line therapy
NR CR/PR CR/PR NR
NR = no response
Second-line therapy for aggressive NHL
Ideal second-line therapy
– provides effective cytoreduction to achieve an optimal response
– results in minimal non-haematological toxicity
– is not stem-cell toxic
– effectively mobilises stem cells into the peripheral blood
Rituximab significantly improves outcomes when combined with HDT and ASCT
Khouri IF, et al. J Clin Oncol 2005;23:2240–7
OS
Months post-transplant
1.0
0.8
0.6
0.4
0.2
00 3 6 9 12 15 18 21 27 42 30
p=0.004
No rituximab (n=30)
Rituximab (n=67)
p=0.002
No rituximab (n=30)
Rituximab (n=67)
Historical comparison
DF
S
1.0
0.8
0.6
0.4
0.2
0
Months post-transplant
0 3 6 9 12 15 18 21 27 42 30
CORAL study: R-ICE versus R-DHAP followed by ASCT ± maintenance
R1
R-DHAP
Clinical evaluation
R2
Clinicalevaluation
Observation
BEAM ASCT
Rituximab 375mg/m²
every 8 weeks for 12 months
OFF
R-ICE
R-DHAP
R-ICER-DHAP
R-ICE
PBPC
PD/SD
CR/PR
Hagberg H, et al. Ann Oncol 2006;17(Suppl. 4):iv31–iv32
400 patients neededRecruitment complete
*With lenograstim 150µg/m²R-ICE = rituximab, ifosfamide, carboplatin, etoposideR-DHAP = rituximab, dexamethasone, ara-c, cisplatinPBPC = peripheral blood progenitor cell
*With lenograstim 150µg/m²R-ICE = rituximab, ifosfamide, carboplatin, etoposideR-DHAP = rituximab, dexamethasone, ara-c, cisplatinPBPC = peripheral blood progenitor cell
CORAL toxicity
R-ICEn, (%)
R-DHAPn, (%)
Infection with neutropenia Grade 3–4 Yes 16 (17) 18 (21)
Infection without neutropenia Grade 3–4 Yes 6 (7) 8 (9)
Renal Grade 3–4 Yes 0 6 (7)
CORAL efficacy
ResponseR-ICE/R-DHAP
(%) p value
CR/CRu/PR ORR 66/70 0.8
CR/CRu 42/40 0.8
MARR
CR/CRu/PR 55/64 0.2
Cru = unconfirmed CRORR = overall response rateMARR = mobilization adjusted response rate
Cru = unconfirmed CRORR = overall response rateMARR = mobilization adjusted response rate
Response rate prognostic factors CR/CRu/PR: logistic model
p value
Prior rituximab 0.1
Relapse <12 months 0.0002
IPI >1 0.003
Treatment arm 0.1
Efficacy analysis: secondary criteriaEFS – ITT
GELA data on file
1.0
0.8
0.6
0.4
0.2
0
Su
rviv
al p
rob
abil
ity
0 10 20 30 40EFS (months)
No. of subjects Event Censored Median survival (95% CI)Arm A/R-ICE 100 49% (49) 51% (51) 20.96 (9.26 NYR)Arm B/R-DHAP 94 44% (41) 56% (53) NA (8.51 NYR)
Log-rank p=0.4589
Arm A/R-ICEArm B/R-DHAP
NYR = not yet reached; CI = confidence interval; ITT = intent to treat
Prognostic factors failure EFS
GELA data on file
1.0
0.8
0.6
0.4
0.2
0
Su
rviv
al p
rob
abil
ity
0 10 20 30 40EFS (months)
Log-rank p<0.0001
<12 months12 months
No. of subjects Event Censored Median survival (95% CI)<12 months 108 60% (65) 40% (51) 5.45 (3.61 10.15) 12 months 86 29% (25) 71% (53) NA (27.47 NA)
Maintenance
Maintenance in responding patients has proven efficacy in follicular lymphoma and mantle cell lymphoma
Role in more aggressive lymphomas?
It might be easier to demonstrate a difference in PR or relapsed patients
Week
Week
ACVBP
AC/ACE
Arm A
Arm B
0 2 4 6
I II III IV
AC ACE ACEACE
Induction
0 2 4 6
Leukaphereses
MTX21 22 23 24
Rituximab375mg/m2
Observation
day 60
d’ 0day 0
10 12
Response
day 80–90
Autotransplant (ASCT)
Response
Response50%R1
day 45–60
CBV-Mitox
Haioun C, et al. J Clin Oncol 2007;25(Suppl. 18):444s (Abstract 8012)Haioun C, et al. J Clin Oncol 2007;25(Suppl. 18):444s (Abstract 8012)
Can we reduce post transplant relapse rate? NHL 98-B3 study: design
Mitox = mitoxantrone
R2
*Calculated from randomisation for post-HDT treatment
Median follow-up from R2*: 4 years
Rituximab: 80% (95% CI: 72–86)Observation: 71% (95% CI: 62–78)
n=139
n=130
p=0.098
EFS according to post-HDT treatment arm (ITT analysis, n=269)
1.0
0.8
0.6
0.4
0.2
0
Su
rviv
al p
rob
abil
ity
0 1 2 3 4 5 6
p=0.0989
ObservationRituximab
Years
Haioun C, et al. J Clin Oncol,2007;25(Suppl. 18):444s (Abstract 8012)
CR CRu + PR
n=70
n=60
n=69
n=70
Rituximab: 86% (95% CI: 75–92)Observation: 68% (95% CI: 53–79)
Rituximab: 74% (95% CI: 62–83)Observation: 73% (95% CI: 61–82)
p=0.023 p=0.916
EFS by post-HDT response status
Haioun C, et al. J Clin Oncol 2007;25(Suppl. 18):444s (Abstract 8012)
1.0
0.8
0.6
0.4
0.2
0
Su
rviv
al p
rob
abil
ity
1.0
0.8
0.6
0.4
0.2
0
Su
rviv
al p
rob
abil
ity
0 1 2 3 4 5 6 0 1 2 3 4 5 6
Years Years
ObservationRituximab
ObservationRituximab
Rituximab maintenance following HDT and autologous cell rescue after R-ICE
cytoreduction improves EFS and OS
Retrospective analysis Patients treated with R-ICE
1999–2006 Who had PR or CR No rituximab (n=38) Rituximab weekly x 4 at day 42 plus
day 180 (n=26) Rituximab every 8 weeks x 6 starting
on day 29 (n=17)
Multivariate analysis Disease status (p=0.04) and Rituximab maintenance (p=0.003) Were significant for OS Only maintenance rituximab Was significant for EFS (p<0.001)
Rice RD, et al. Blood 2007;110:385a (Abstract 1280)
EFS1.0
0.8
0.6
0.4
0.2
0
Pro
po
rtio
n e
ven
t fr
ee
0 1 2 3 4 5 6 7Years
Maintenance (n=43)
No maintenance (n=38)
p=0.0002
Conclusion
Rituximab has completely transformed the outcome of patients with DLBCL
R-CHOP is the most widely used regimen
Prognostic parameters with R-CHOP need some redefinition
New molecules?– combination with another drug having a different
mechanism of action (targeting a different intracellular pathway) looking for a synergy
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