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

Thank Youfor attention!