rituximab in children with b-nhl on top of bfm95 protocol paediatric oncology and haematology...
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Rituximab in children with B-NHL on top of
BFM95 protocol
Paediatric Oncology and Haematology Research Institute
N.N.Blokhin Russian Cancer Research CenterMoscow
Т.Т.Valiev, A.V.Popa, G.L.Mentkevich
Results of multicenter studies on III/IV stages
childhood B-NHLProtocol EFS (3-5y) AuthorsBFM90 69.1% Meng JH et al. 2012
POG Total 79%B-ALL – 65%
Bowman WP et al. 1996
CCG Hybrid 60% incl B-ALL Cairo MS et al. 2002
NHL-BFM90 73%B-ALL 74%
Reiter A et al. 1999
NHL-BFM95 81%B-ALL 77%
Woesserman W. et al. 2005
FAB/LMB96 79% Patte C. et al. 2007
EFS in pediatric pts with B-NHL in Russia (2004)
Вероятность
Е.В.Самочатова, Н.В.Мякова и др. Гематология и трансфузиология»,2004,№1,с.3;
годыР=0,035
Literature data are limited
3-year EFS in children with B-NHL III/IV stages treated by FAB/LMB96 (R+) - 95%
FAB/LMB96 (R-) – 84%
Goldman , ASH, Abstract No 2702, 2011
Overall response rate 41%
Rituximab toxicity (grade III/IV)
-General condition 15%-Fatigue 13%-ALT/AST 8%-Anaphylaxis 7%-Infection 3%
B-NHL-BFM 95 protocol modification(Italian experience)
(A.Rosolen, M.Pillon, L.Mussolin 2012)
Modified B-NHL BFM95 protocol
(rituximab regimen) 2007-2010
4 risk group
AA BB CC AA BB CC
3 risk group
АА ВВ СС АА ВВ
Patients characteristicsR+
(n=28)R-
(n=25)
Age 3-17y (median 8,2y)
3-16 y (median 7,8y)
m/f 23/5 22/3
BL 23 (82%) 21 (84%)
DLBCL 2 (7%) 2 (8%)
PMBCL 3 (11%) 2 (8%)
Stage III 19 (68%) 15 (60%)
IV 9 (32%) 10 (40%)
Risk group 3 12 (43%) 11 (44%)
4 16 (57%) 14 (56%)
BM+ 12 (43%) 8 (32%)
CNS+ 3 (11%) 2 (8%)
CD20+ 28 (100%) 25 (100%)
Results of modified B-NHL BFM95 protocol
(rituximab regimen)
EFS= 94,4+/-4,3% R+ (n=28)(median 73,7+/-4,3 мo)
EFS= 74,8+/-9,7% R- (n=25)(median 119,8+/-8,7
мo)
EFS in group with M1 – 91,9% EFS in group without M1 –
92,5%
Modified B-NHL BFM95(rituximab regimen, block reduction)
2010-…
4 risk group
AA BB CC AA BB
3 risk group
АА ВВ СС АА ВВ
Comparative analysis of block reduction and standard block
therapy with rituximab
Block reductionR+
(n=10)
Standard block therapy R+
(n=23)
BL 10 (100%) 23 (100%)
Stage III 6 14
IV 4 9
Risk group 3 0 8
4 10 (100%) 15
Alive(duration)
9/10(24 mo)
22/23(72 mo)
Relapse 0 0
Progression 1 0
Induction death 1 1
Treatment failure for B-NHL BFM95 protocol (rituximab regimen)
Failure R+(n=38)
R-(n=25)
Progression 1 (3%) 2 (8%)Relapse 0 (0%) 1 (4%)TRD 2 (5%) 3 (12%)
Treatment toxicity for B-NHL BFM95 protocol (rituximab regimen)
Toxicity R+(n=38)
R-(n=25)
Haematologic grade ¾
37 (97%) 23 (92%)
Transfusions 36 (95%) 22 (88%)Mucositisgrade 3/4ст
38 (100%) 24 (96%)
Febrile neutropenia
38 (100%) 25 (100%)
Conclusions
1. Rituximab with B-NHL BFM95 protocol as a first-line treatment in children with B-NHL (unfavorable stages and risk groups) increased EFS significantly
2. Toxicity profile of rituximab regimen was comparable with standard B-NHL BFM95 protocol
3. It is possible to reduce block number for pts with B-NHL R4 with early complete response from six to five
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