Linfomi IndolentiLa terapia: prima
linea, salvataggio,ruolo del
mantenimento
Corrado Tarella
S.C.U. Ematologia e Terapie Cellulari
A.O. ORDINE MAURIZIANO, Torino e
UNIVERSITA’ DEGLI STUDI DI TORINO
Follicolari
La terapia diprima linea
Incidence of various non Hodgkinlymphoma subtypes
FCLnon follicular low grade NHL
B-cell DLCLT-cell NHL
Other lymphomas
30%
6%16% 28%
20%
Div. Univ. Di Ematologia di TorinoIncidenza dei sottotipi di linfoma tra 500 pazienti
trattati negli ultimi 10 anni
Sottotipi NHL B
1%1%2% 2%3% 4%7%
10%
22%
48%
Hcl
Altri istotipi
Burkitt
Waldenstrom
MALT
MZL
MCL
CLL
FCL
DLCL
22 %
Follicular LymphomaInternational Prognostic Index
Prognostic factors:
1. Age (> 60 years)2. Ann Arbor stage3. Hb level (< 12 gr/dl)4. N° nodal areas (> 4)5. LDH level
Bcl-2/IgH mcr 9%
No evidence of Bcl2/IgH26%
PCR analysis of Bcl2/IgH in FL-NHL
at diagnosis
Bcl-2/IgH MBR 65%
represents the main improvement in therepresents the main improvement in the
management of B-cell lymphoma over themanagement of B-cell lymphoma over the
last 20 yearslast 20 years
The anti-CD20 Monoclonal AntibodyRituximab
Randomized studies in patients with follicular lymphoma using rituximab plus chemotherapy
Salles G., Hematology 2007
before deciding the therapy for patientswith indolent NHL, lymphoid tissue shouldbe tested for CD20 antigen expressionCD20 antigen expression
patients with stage I-II diseasestage I-II disease and low-tumor burden, should receive externalinvolved field radiotherapy onlyradiotherapy only [grade B]at the dose of 30-36 Gy. Adjuvantchemotherapy is not recommended inthese patients [grade D]
no indication for Rituximab aloneRituximab alone inthese clinical conditions ??
Rituximab Combined with Localized Radiotherapy as Front-Line Therapyin Limited Stage Low-Grade Lymphoma Patients
the Torino experience
since March 1999March 1999 through April 2009April 2009, 25 consecutive low-gradelymphoma patients with stage I-II presentation entered theRituximab+IF-RT treatment program
treatment included 44 weekly doses of RituximabRituximab at 375 mg/sqmfollowed by IF-RTIF-RT, with a median radiation dose of 36 Gy36 Gy (range 25-40)
the 5-yr. Overall SurvivalOverall Survival projections is 93%93%
with a 5-yr Failure-Free SurvivalFailure-Free Survival projection of 81%81%
advanced-stageadvanced-stageFollicularLymphoma
when and how towhen and how totreattreat
Criteria for starting a cytotoxic treatmentin patients with follicular lymphoma
Salles G., Hematology 2007
advanced-stageadvanced-stageFollicularLymphoma
when and how towhen and how totreattreat
Randomized studies in patients with follicular lymphoma using rituximab plus chemotherapy
Salles G., Hematology 2007
TIME TO TREATMENT FAILURE AFTER START OFTHERAPY FOR CHOP OR R-CHOP
Hiddemann et al, Blood 2005
Table 2. Outcomes associated with R-CVP vs. R-CHOP
Parameter Phase III CVP Clinical Trial Phase II CHOP Phase III CHOP
ORR 81% 100% 96%% CR 41% 87% 20%**TTP (median) 27 mos 82.3 mos NR*
Abbrviations: R-CVP, Rituximab + Cyclophosphamide + Vincristine + Prednisone; R-CHOP, Rituximab + Cyclophosphamide + Doxorubicin + Vincristine + Prednisone; ORR,overall response rate; CR, complete response; TTP, time-to-progression
* Not reached at median follow-up of 20 months (i.e., 80% of R-CHOP patients still inremission)
** Discrepancy between CR rates noted from phase II vs. phase III R-CHOP trials areaddressed later in this article and are likely secondary to differences in baseline prognosticfactors and patient entry criteria
PCR on BM and PB
Rituximab 375 mg/mRituximab 375 mg/m22 g 1 (g 8 ciclo I) g 1 (g 8 ciclo I) Fludarabine 25 mg/mFludarabine 25 mg/m2 2 gg 2-4gg 2-4Mitoxantrone 10 mg/mMitoxantrone 10 mg/m22 g 2 g 2Dexamethasone 10 mg gg 2-4Dexamethasone 10 mg gg 2-4
Clinical and molecular follow-up(12, 18, 24, 30, 36, 42 months)
R- FND x 4 once a month
Rituximab x 4 once a week
PCR on BM and PB
CR/PCR+/- or PR
NR OFF
RANDOM
Rituximab maintenance x 4 at months 9, 11, 13, 15
Observation
PCR on BM and PB
Studio ML17638 IIL ID: IILFL04Abs# 1278 Abs# 1278 Vitolo et al
INTERIM ANALYSIS: 80/95 pts randomized in ORRINTERIM ANALYSIS: 80/95 pts randomized in ORR
54%
37%
2%0,00%
CR PR SD
71%
13%7%
0,00%
CR PR SD/PD
CR
PR
SD/PD
Clinical response: ORR 84% after R-FND + RClinical response: ORR 84% after R-FND + R
After R-FND x 4 - Month 5-6After R-FND x 4 - Month 5-6 After Rituximab x 4 - Month 8After Rituximab x 4 - Month 8
Molecular responseMolecular response
After R-FND x 4After R-FND x 4Month 5-6Month 5-6
Bcl-2 neg 51%Bcl-2 neg 51%
After Rituximab x 4After Rituximab x 4Month 8Month 8
Bcl-2 neg 71%Bcl-2 neg 71%BaselineBaseline
Copyright © American Society of Clinical Oncology
Rummel, M. J. et al. J Clin Oncol; 23:3383-3389 2005
Bendamustine hydrochloride
Bendamustine plus Rituximab versus CHOP plus Rituximab in the First-Bendamustine plus Rituximab versus CHOP plus Rituximab in the First-
Line Treatment of Patients with Indolent and Mantle Cell Lymphoma Line Treatment of Patients with Indolent and Mantle Cell Lymphoma ––
Final Results of a Randomized Phase III Study of theFinal Results of a Randomized Phase III Study of the
StiL (Study Group indolent Lymphomas, Germany)StiL (Study Group indolent Lymphomas, Germany)
Mathias J. Rummel, N. Niederle, G. Maschmeyer, G. A. Banat, U. von Grünhagen,Mathias J. Rummel, N. Niederle, G. Maschmeyer, G. A. Banat, U. von Grünhagen,
C. Losem, G. Heil, M. Welslau, C. Balser, U. Kaiser, H. Ballo, E. Weidmann,C. Losem, G. Heil, M. Welslau, C. Balser, U. Kaiser, H. Ballo, E. Weidmann,
H. Dürk, D. Kofahl-Krause, F. Roller, J. Barth, D. Hoelzer, A. Hinke,H. Dürk, D. Kofahl-Krause, F. Roller, J. Barth, D. Hoelzer, A. Hinke,
and W. Brugger and W. Brugger ..
on behalf of the StiL on behalf of the StiL
Blood 114: 168 (abstr #405), 2009 . Blood 114: 168 (abstr #405), 2009 .
Bendamustine-Rituximab (B-R) vs CHOP-R
Bendamustine-RituximabBendamustine-Rituximab
CHOP-RituximabCHOP-Rituximab
FollicularFollicularWaldenströmsWaldenströmsMarginal zoneMarginal zoneSmall lymphocyticSmall lymphocyticMantle cellMantle cell
RR
StiL NHL 1-2003 StiL NHL 1-2003
Bendamustine 90 mg/mBendamustine 90 mg/m22 day 1+2 + R day 1, max 6 cycles, q 4 wks. day 1+2 + R day 1, max 6 cycles, q 4 wks.
CHOP-R, max 6 cycles, q 3 wks.CHOP-R, max 6 cycles, q 3 wks.
MJRMJR
Inclusion criteria : B-R vs CHOP-RInclusion criteria : B-R vs CHOP-R
Patients with one of the following CD20 positive lymphoma entitiesPatients with one of the following CD20 positive lymphoma entities - follicular lymphoma, grade 1 and 2- follicular lymphoma, grade 1 and 2 - lymphoplasmacytic lymphoma / Immunocytoma (Waldenström) - lymphoplasmacytic lymphoma / Immunocytoma (Waldenström) - small lymphocytic lymphoma (CLL without leukemic phase) - small lymphocytic lymphoma (CLL without leukemic phase) - nodular and generalized (nodal und extranodal) marginal zone lymphoma - nodular and generalized (nodal und extranodal) marginal zone lymphoma - mantle cell lymphoma - mantle cell lymphoma
No pretreatment with chemotherapeutics, Interferon or RituximabNo pretreatment with chemotherapeutics, Interferon or Rituximab
Defined indication for treatment, except in mantle cell lymphomaDefined indication for treatment, except in mantle cell lymphoma
Histology not older than 6 monthsHistology not older than 6 months
Stage III or IVStage III or IV
Age at least 18 years, no upper age limit, WHO 0-2Age at least 18 years, no upper age limit, WHO 0-2
Written informed consent of the patientWritten informed consent of the patient
MJRMJR
Defined Indications for treatmentDefined Indications for treatment
B-symptomsB-symptoms
Hematopoietic failureHematopoietic failure(Hb < 11 g/dl, granulocytes < 1.500 /µl, thrombocytes < 100.000 /µl)(Hb < 11 g/dl, granulocytes < 1.500 /µl, thrombocytes < 100.000 /µl)
Large tumor burdenLarge tumor burden(3 areas > 5 cm or 1 area > 7.5 cm)(3 areas > 5 cm or 1 area > 7.5 cm)
Rapid progressionRapid progression(increase of tumor mass > 50% within 6 months)(increase of tumor mass > 50% within 6 months)
Complications due to diseaseComplications due to disease(pain, infarction of spleen, hyperviscosity syndrome, etc.)(pain, infarction of spleen, hyperviscosity syndrome, etc.)
MJRMJR
549 patients randomized. 513 patients evaluable for response and toxicity549 patients randomized. 513 patients evaluable for response and toxicity
B-R CHOP-R Age B-R CHOP-R Age
Total nTotal n 260260 253253 64 64
FollicularFollicular 54 % 54 % 139139 140140 6060
Mantle cellMantle cell 18 %18 % 4545 4848 7070
Marginal zoneMarginal zone 13 %13 % 3737 3030 6666
WaldenströmsWaldenströms 8 %8 % 2222 1919 6464
SLLSLL 4 %4 % 1010 1111 6868
UnclassifiableUnclassifiable 2 %2 % 77 55 6969
EntitiesEntities
MJRMJR
B-R CHOP-R B-R CHOP-R (n=260) (n=253)(n=260) (n=253)
Age (median)Age (median) 64 yrs64 yrs 63 yrs63 yrs
> 70 yrs. > 70 yrs. 23 %23 % 23 %23 %
Stage IVStage IV 77 %77 % 77 %77 %
Bone marrowBone marrow 68 %68 % 67 %67 %
B-Symptoms B-Symptoms 38 %38 % 29 %29 %
LDH > 240 U/lLDH > 240 U/l 38 %38 % 34 %34 %
Bulky diseaseBulky disease 27 %27 % 29 %29 %
IPI > 2 IPI > 2 37 %37 % 34 %34 %
FLIPI 0-1 FLIPI 0-1 12 %12 % 19 %19 %FLIPI 2 FLIPI 2 42 %42 % 33 % 33 % FLIPI FLIPI >> 3 3 46 %46 % 48 %48 %
Patient characteristicsPatient characteristics
n = 279n = 279
Progression free survivalProgression free survival
B-RB-R
CHOP-RCHOP-R
0.00.0
0.10.1
0.20.2
0.30.3
0.40.4
0.50.5
0.60.6
0.70.7
0.80.8
0.90.9
1.01.0
Pro
babi
lity
Pro
babi
lity
00 1212 2424 3636 4848 6060 72 months72 months
B-R: 54,9 vs CHOP-R: 34,8 months (median)B-R: 54,9 vs CHOP-R: 34,8 months (median)
HR = 0.57 (95% CI: 0.43 - 0.76) HR = 0.57 (95% CI: 0.43 - 0.76)
p = 0.00012p = 0.00012
Median observation period 34 months Median observation period 34 months Rummel et al.: Rummel et al.: Blood 114: 168 (abstr #405), 2009Blood 114: 168 (abstr #405), 2009
Progression free survival follicular lymphomaProgression free survival follicular lymphoma
0.00.0
0.10.1
0.20.2
0.30.3
0.40.4
0.50.5
0.60.6
0.70.7
0.80.8
0.90.9
1.01.0
Pro
babi
lity
Pro
babi
lity
00 1212 2424 3636 4848 6060 72 months72 months
B-RB-R
CHOP-RCHOP-R
B-R: not reached vs CHOP-R: 46,7 months (median)B-R: not reached vs CHOP-R: 46,7 months (median)
HR = 0.63 (95% CI: 0.42 - 0.95) HR = 0.63 (95% CI: 0.42 - 0.95)
p = 0.0281p = 0.0281
Rummel et al.: Rummel et al.: Blood 114: 168 (abstr #405), 2009Blood 114: 168 (abstr #405), 2009
Overall SurvivalOverall Survival
00 1212 2424 3636 4848 6060 7272 84 months84 months
0.00.0
0.10.1
0.20.2
0.30.3
0.40.4
0.50.5
0.60.6
0.70.7
0.80.8
0.90.9
1.01.0
Pro
babi
lity
Pro
babi
lity
Bendamustine-R vs CHOP-RBendamustine-R vs CHOP-R
ConclusionConclusion
Bendamustine plus Rituximab has the potentialBendamustine plus Rituximab has the potential
to become a treatment of 1to become a treatment of 1stst-choice in these-choice in these
disease entitiesdisease entities
The issue of “response assessment” is ofparticular relevance whenever CR achievementis the ultimate treatment goal, i.e. whenever CR
is required for a curative outcomecurative outcome
aggressive lymphoma (DLCL, BL)Hodgkin’s Lymphoma Follicular Lymphoma
since the availability of new treatment armaments, namely thehumanized MoAbs, CR achievement is a major end-point
in the management of most lymphoma patients
……..the value of Molecular Remission achievement in FL..the value of Molecular Remission achievement in FL
Minimal residual disease monitoring afterCHOP followed by rituximab forpreviously untreated indolent NHL
100
90
80
70
60
50
40
30
20
10
0–24 Baseline 12 28 44 weeks
RituximabCHOP
PCR
-pos
itive
pat
ient
s (%
) BM
PB
n=77
n=76
n=73
n=72
Rambaldi A, et al. Blood 2002; 99:856–62
Molecular monitoring of MRD inFL-NHL
after HDT and autologoustransplantation
Turin-group experiencewith the i-HDS scheme
Corradini P et al, Blood 1997 Jan 15;89:724-31Tarella C et al, Leukemia 2000 Apr 14:740-7
a “high-dose” approach, aimed toobtain maximal tumor cytoreductionand to exploit the in vivo-purgingin vivo-purgingeffect operated by chemotherapy
MOLECULAR RESULTS IN LOW GRADELYMPHOMAS
F L(CD10+ CD5-)
HARVESTS FOLLOW-UP
59%41% 62%38%
MCL + SLL(CD10- CD5+)
17%
83%
6%
94%
PCR POSITIVE
PCR NEGATIVE
1st multicenter, prospective GITMO trial
► between December 1996 and February 1999
► 92 FCL patients were enrolled and treated with i-HDS(Rituximab-free) by 20 GITMO Centers
► previously untreated FCL patients were eligible ifpresenting with one or more of the following signs: - bulky disease (greater than 5 cm) - high serum LDH - systemic or disease-related compression symptoms - ECOG performance status ≥ 2 - BM invasion greater than 20%
► preliminary results: Blood 2002
0
10
20
30
40
50
60
70
80
90
100
0 20 40 60 80 100 120
% s
urvi
vng
months
PCR neg
PCR pos
1st multicenter, prospective GITMO trial – 1996PROGRESSION FREE SURVIVALPROGRESSION FREE SURVIVAL
ACCORDING TO FOLLOW-UP STATUSACCORDING TO FOLLOW-UP STATUS
RITUXIMAB-supplemented HDS
versus
RITUXIMAB-supplemented CHOP
Randomized Trial in Poor-risk (aaIPI 2-3) FL at DiseaseOnset, Comparing
Multicenter, Prospective GITMO/IIL trial
Closing date 31.05.2005
Ladetto M et al.: Blood First Edition Paper, prepublished online January 31, 2008
MOLECULAR REMISSION ACHIEVEMENT(at least two PCR-negative samples in a CR patient)
Persistent PCR-positive patients
CHOP-RCHOP-R
44%44%
11/25R-HDSR-HDS
80%80%
28/35
Ladetto M et al.: Blood First Edition Paper, prepublished online January 31, 2008
R-HDS vs CHOP-R RANDOMIZED TRIALEVALUABLE PATIENTS: 60
p<0.001
PCR neg
PCR pos
75% at 4 yrs.75% at 4 yrs.
21% at 4 yrs.21% at 4 yrs.
PFS ACCORDING TO PCR-STATUS
p <0.001
recent update on the long-term outcome of the FLrecent update on the long-term outcome of the FLpatients treated with the HDS schedule in the threepatients treated with the HDS schedule in the threetrials performed over the last 18 yearstrials performed over the last 18 years
single-Center (Torino)phase II study for indolentNHL (1991-1998)
26 patients(advanced-stage +adverse prognostic
factors)
GITMO multicenter phase IIstudy for FL (1996-1999)
92 patients(advanced-stage +adverse prognostic
factors)
GITMO multicenter phase IIIstudy with R+ (2001-2005)
67 F L(aaIPI 2-3aaIPI 2-3)
Total 185 FL185 FL
updated
2626
7979
6565
170 (92%)170 (92%)
at present 120120 patients (70%)(70%) are alivealive
main causes of death were:
77 early (peri-transplant) deaths
25 25 lymphoma progressions
11 11 secondary neoplasms
77 other causes
170 advanced-stage FL patientsOVERALL SURVIVAL
median f.u.: 10 yrs.
69 %81 %
61 %
median survival: not yet reachednot yet reached
2015105years
at present 8282 patients (48% of the whole(48% of the wholeseries)series) are alive in their first Continuousalive in their first ContinuousComplete RemissionComplete Remission (CCR) (CCR)
4747 of them (28%)(28%) are in their first CCRat 8 to 15 yrs.8 to 15 yrs. since HDS
the latest relapselatest relapse has been recorded at 8 yrs.8 yrs.following HDS
among patients in CCR:
3434 are in Molecular RemissionMolecular Remission
2 2 have a ““mixedmixed”” PCR PCR
33 have a PCR +vePCR +ve
170 advanced-stage FL patientsDISEASE FREE SURVIVAL
(events: recurrence and both early and late toxic deaths)
48 %
61 %
48 %
2015105years
PREDICTIVE FACTORSOF THE LONG-TERM OUTCOME
None of the pre-treatment parameters considered hadpredictive value on the long-term outcome, including:
sex - age (borderline) - histology (grade 1-2 vs. 3a)– symptoms – ECOG P.S. – splenomegaly – high LDH –extranodal disease Rituximab addition to HDS
two factors only were highly predictive for aprolonged progression-free survival, i.e. :
CR achievement and Molecular Remission achievement
the Italian experience with intensified programs withautograft in follicular lymphoma
what we have learnt:
the value of Molecular RemissionMolecular Remission (MR) achievementfollowing either conventional and intensifiedchemotherapy, with and w/o Rituximab
the chances of long-term survival, in continuousclinical and molecular remission: FollicularFollicularLymphomaLymphoma a curable diseasea curable disease ?
the need to achieve maximal tumor reductionmaximal tumor reduction whilereducing treatment toxicityreducing treatment toxicity in the primary treatmentof Follicular Lymphoma
Gitmo-IIL study: 61% at 16 yrs.
the steps forward in the treatmentstrategy for Follicular Lymphoma:
to try to achieve CR alongto try to achieve CR alongwith MR,with MR,
by combining Rituximab withby combining Rituximab withconventional chemotherapyconventional chemotherapy
exploiting HDT and autograft for theexploiting HDT and autograft for therescue of refractory/relapsed patients,rescue of refractory/relapsed patients,including those unable to achieveincluding those unable to achieveclinical and molecular remissionclinical and molecular remission
FINAL CONSIDERATIONS
• …however, CHOP-R is not yet an optimal strategy, atleast for high-risk FL
• at present, the favored strategy for FL may be the use ofR-CHOP as induction, even in high-risk patients
early inclusion of additional therapy, includingeither Rituximab-maintenance or intensive
chemo-immunotherapy with autograft in case ofsigns of treatment failure ?
….or even the allogeneic optionallogeneic option, at least foryounger patients with highly unfavourable
clinical presentation ?
ACKNOWLEDGEMENTS
Div. of Hematology -University of TorinoDir. Prof. M. BoccadoroLymphoma Team:Daniele CaraccioloLuciana BerguiPaolo GavarottiFederica De MarcoAngela GueliMarco Ruella
Alessandro PileriPaolo CorradiniMarco Ladetto
Statistical work byRoberto Passera
Tandem Autologous – AllogeneicNonmyeloablative Sibling Transplant inRelapsed Follicular Lymphoma Leads to
Impressive Progression Free Survival withMinimal Toxicity
Sandra Cohen, Lambert Busque, Thomas Kiss, GuySauvageau ,Thomas Kiss, Silvy Lachance, Denis-
Claude Roy, Jean Roy.Maisonneuve Rosemont Hospital
University of MontrealMontreal, Canada
Treatment planStem cell mobilization:
Cyclophosphamide (Cy) 1.5g/m2 + G-CSF 5µg/kg BID
Autologous transplant:BEAM or BEAC
Nonmyeloablative allogeneic transplant:Fludarabine 30mg/m2/d + Cy 300mg/m2/d x 5d
Tacrolimus D -8 to +50 (10-15 nmol/L) → tapered by D +100Mycophenolate mofetil 1g BID D+2 to +50
3 months
N=27
Median Follow-up 37 months
1 patient has died from GVHD at +11 months1 patient has died from GVHD at +11 months
to date, there has been no disease progression to date, there has been no disease progression
18 (67%) pts developed extensive chronic GVHD 18 (67%) pts developed extensive chronic GVHD
Adding Rituximab to chemotherapy significantlyExtends Survival Without Increasing Toxicity in
Patients With Follicular LymphomaFollicular Lymphoma
Time to treatment failure
67 43 29 14 13 9 1 0 0159 100 87
114 95 73 50 37 20 8 3 0162 140 123
CVP
R-CVP
Patients at risk
1.0
0.8
0.6
0.4
0.2
00 3 6 9 12 15 18 21 24 27 30 33
Study month
Even
t-fre
e pr
obab
ility
R- CVP: median 26 months
CVP: median 7 monthsp<0.0001
18 months follow-up Marcus et al, Blood 2005, 105: 1417
the the possible use of possible use of rituximab monotherapyrituximab monotherapyin patients with advanced stage FL,in patients with advanced stage FL,potentially manageable with a watchfulpotentially manageable with a watchfulwaiting approachwaiting approach
[486] Single Treatment with Rituximab Monotherapy for Low-Tumor[486] Single Treatment with Rituximab Monotherapy for Low-TumorBurden Follicular Lymphoma (FL): Survival Analyses with ExtendedBurden Follicular Lymphoma (FL): Survival Analyses with ExtendedFollow-Up (F/Up) of 7 Years. Session Type: Oral SessionFollow-Up (F/Up) of 7 Years. Session Type: Oral Session
Philippe Colombat, Nicole Brousse, Franck Morschhauser, Patricia Franchi-Rezgui,Philippe Colombat, Nicole Brousse, Franck Morschhauser, Patricia Franchi-Rezgui,Pierre Soubeyran, Vincent Delwail, Eric Deconinck, Corinne Haioun, CharlesPierre Soubeyran, Vincent Delwail, Eric Deconinck, Corinne Haioun, CharlesFoussard, Catherine Sebban, Herve Tilly, Noel-Jean Milpied, Francois Boue, Jean-Foussard, Catherine Sebban, Herve Tilly, Noel-Jean Milpied, Francois Boue, Jean-Michel Karsenti, Pierre Lederlin, Albert Najman, Catherine Thieblemont, DelphineMichel Karsenti, Pierre Lederlin, Albert Najman, Catherine Thieblemont, DelphineMoreau, Loic Bergougnoux, Gilles Andre Salles, Philippe Solal-CelignyMoreau, Loic Bergougnoux, Gilles Andre Salles, Philippe Solal-Celigny
Patients with stage III-IVdisease and not candidate to awatch and wait strategy shouldbe treated with frontlinechemotherapy [grade BB]
PFS IN PCR + and PCR -ACCORDING TO TREATMENT ARM
%
surv
ivin
g
%
surv
ivin
g
p = N S p = N S
Ladetto M et al.: Blood First Edition Paper, prepublished online January 31, 2008
the extremely good outcome of patients achievingMR is unrelated to treatment arm
Time To Next TreatmentTime To Next Treatment
00 1212 2424 3636 4848 6060 7272 84 months84 months
0.00.0
0.10.1
0.20.2
0.30.3
0.40.4
0.50.5
0.60.6
0.70.7
0.80.8
0.90.9
1.01.0
Pro
babi
lity
Pro
babi
lity
B-RB-R
CHOP-RCHOP-R
B-R: not reached vs CHOP-R: 37,5 months (median)B-R: not reached vs CHOP-R: 37,5 months (median)
HR = 0.52 (95% CI: 0.38 - 0.70) HR = 0.52 (95% CI: 0.38 - 0.70)
p = 0.00002p = 0.00002
Rummel et al.: Rummel et al.: Blood 114: 168 (abstr #405), 2009Blood 114: 168 (abstr #405), 2009
Front-line therapy with rituximab added to thecombination of cyclophosphamide, doxorubicin,vincristine and prednisone (CHOP) significantly improvesthe outcome of patients with advanced stage follicularlymphomas as compared to CHOP alone - results of aprospective randomized study of the german low gradelymphoma study group (GLSG)
Hiddemann W, Kneba M, Dreyling M et alBloodBlood 2005 Dec 1; 106(12): 3725-32
L’importanza della accurata Valutazione
della risposta al trattamento
L’impiego sempre più esteso della P E TP E T
La valutazione in PCRPCR della MalattiaMinima Residua (M R DM R D) nei casi BM+