Bertrand Coiffier Service d Hématologie Hospices Civils de Lyon Equipe Pathologie des Cellules Lymphoïdes UMR 5239 CNRS UCB ENS HCL The Lymphoma Study Association One question lot of possibilities ID: 776660
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Slide1
Future directions: Can we improve outcomes in relapsed/refractory DLBCL or aggressive NHL?
Bertrand Coiffier
Service d’HématologieHospices Civils de Lyon
Equipe
« Pathologie des Cellules Lymphoïdes »
UMR 5239 CNRS – UCB – ENS - HCL
The Lymphoma
Study Association
Slide2One question, lot of possibilities
Outcome different according to settings, so treatment objectives are different
Relapse or refractory
First or later progression
Young or old
When is it palliative treatment?
When the objective is CR?
Slide3Refractory patients
Patients who progress during chemotherapy (first line or later)
Patients who progress a few months after responding to chemotherapy
6, 9, or 12 months?
Always associated with poor outcome
But not true for 20% to 30% of the “refractory” patients
Slide4Studies with/without rituximab
Without rituximab
With rituximab
Slide512 m
9
m
15 m
Effect of modifying the threshold between early and late relapse
Slide6Same observation in Italy
Tarella
et al. ASH 2012 Abst. 305
- 2543 patients
- All subtypes of lymphoma
- 46% DLBCL
Slide7N=160
N=228
31%
64%
N=147
N=241
30%
62%
Gisselbrecht C et al. JCO 2010;28:4184-4190
PFS
according
to major
prognostic
factors
Time from primary diagnosisto failure
Rituximab use
at
first line
Slide8GAUGUIN aNHL Phase II: End-of-treatment response in rituximab-refractory patients
Rituximab refractory defined as patients who had a response of < 6 months or who failed to respond to a rituximab-containing regimen (rituximab monotherapy or in combination with chemotherapy)
0
20
40
60
80
100
All
1,600/800 mg
400/400 mg
Patients (%)
n = 25
n = 13
n = 12
ORR, n (%)
4 (16)
1 (8)
3 (25)
CR
0
0
0
CRu
0
0
0
PR413
63% of patients were previously refractory to a rituximab-containing regimen
CR
CRu
PR
16%
8%
25%
Slide9Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma
A
Younes et al. JCO 2012;30:2183
Slide1010
IRC Responses by Type of Prior Therapy
*denileukin diftitox, interferon.
Other
Slide11Relapsed patients
Patients who responded to prior line of therapy (CR or PR)Some can be salvaged in 2nd line45-50% in young patients1Around 20% 2-year OS in elderly patientsNo good data for 3rd line
1
Gisselbrecht
et al. JCO 2012
Slide1298-5 study: OS of relapsing patients
Median: 6 months
5-y OS: 15 & 20%
Slide13First take home message
Poor survival after progression in DLBCL
However, 20% to 50% of the patients can be salvage, depending on age
Even in primary refractory patients
Except for unfit patients, a second line therapy is mandatory
With the objective of cure or long term survival
Slide14Which therapy (young patients)?
Objective in first progression: CR before transplant
CORAL: R-DHAP seems a little better than ICE
Other regimens? RIT?
No proven benefit of maintenance/consolidation
Other progressions: try allogeneic transplant if good response to salvage
Slide15Which therapy (older patients)?
Older = Not fit for transplant
A few regimens: R-GemOx
Phases II of #50 patients
ORR 60%-80%
CR 30%-40%
Median PFS #9 months
Median OS # 12-18 months
Rituximab improves response
Slide16Blood 2008;111:537
225 patients
Slide1746 patients
ORR 83%
CR 50%
R-GemOx
Slide1848 DLBCL patients, ORR 60%, CR 44%
R-GemOx Phase II from GELA
PFS
O
S
Slide19Eur
J
Haematol 2008;80:127
32 patients, ORR 43%, CR 34%
Slide20Other regimens
Numerous new “targeted” drugs in phase II
Slide21Other multidrug regimens
Lenalidomide & rituximab1Bendamustine & rituximab2ADC & rituximab3…Usually no efficacy in refractory patients
1 Zinzani et al. Clin Lymph Myel Leuk 2011;11:462; 2 Horn et al. Ann Hematol 2012;91:1579; 3 Fayad et al. J Clin Oncol 2013;on line
Slide22Regimens for refractory patients
No studies directed specifically these patients,
particularly in first line
Even if it is the big challenge in DLBCL
Always mixed with relapsed patients
Rending interpretation very difficult
Slide23Slide24Conclusion for relapsed patients
Incidence decreases with new regimens
Try to cure young ones at time of relapse with salvage and
autotransplant
Not really a place for allogeneic transplant in first relapse
Best regimen for salvage to be defined
R-CT + new agent(s)
No demonstrated role for maintenance
Slide25Conclusion for refractory patients
In first line, try to recognize them early on
Same problem for truly refractory or early progression
Design specific studies addressing this problem
Introduce new agents