Rituximab in children with B-NHL on top of BFM95 protocol Paediatric Oncology and Haematology Research Institute N.N.Blokhin Russian Cancer Research Center Moscow Т.Т.Valiev, A.V.Popa, G.L.Mentkevich

Results of multicenter studies on III/IV stages childhood B-NHL ProtocolEFS (3-5y)Authors BFM9069.1%Meng JH et al POG Total79% B-ALL – 65% Bowman WP et al CCG Hybrid60% incl B-ALLCairo MS et al NHL-BFM9073% B-ALL 74% Reiter A et al NHL-BFM9581% B-ALL 77% Woesserman W. et al FAB/LMB9679%Patte C. et al. 2007

EFS in pediatric pts with B-NHL in Russia (2004) ВероятностьВероятность Е.В.Самочатова, Н.В.Мякова и др. Гематология и трансфузиология»,2004,№1,с.3; годы Р=0,035

Literature data are limited 3-year EFS in children with B-NHL III/IV stages treated by FAB/LMB96 (R+) - 95% 3-year EFS in children with B-NHL III/IV stages treated by FAB/LMB96 (R+) - 95% FAB/LMB96 (R-) – 84% FAB/LMB96 (R-) – 84% Goldman, ASH, Abstract No 2702, 2011 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) risk group AA BB CC AA BB CC 3 risk group АА ВВ СС АА ВВ

Patients characteristics R+ (n=28) R- (n=25) Age3-17y (median 8,2y)3-16 y (median 7,8y) m/f23/522/3 BL23 (82%)21 (84%) DLBCL2 (7%)2 (8%) PMBCL3 (11%)2 (8%) Stage III19 (68%)15 (60%) IV9 (32%)10 (40%) Risk group 312 (43%)11 (44%) 416 (57%)14 (56%) BM+12 (43%)8 (32%) CNS+3 (11%)2 (8%) CD20+28 (100%)25 (100%)

odified B-NHL BFM95 protocol (rituximab regimen) 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 reduction R+ (n=10) Standard block therapy R+ (n=23) BL10 (100%)23 (100%) Stage III614 IV49 Risk group (100%)15 Alive (duration) 9/10 (24 mo) 22/23 (72 mo) Relapse00 Progression10 Induction death11

Treatment failure for B-NHL BFM95 protocol (rituximab regimen) FailureR+ (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) ToxicityR+(n=38)R-(n=25) Haematologic grade ¾ 37 (97%) 23 (92%) Transfusions 36 (95%) 22 (88%) Mucositis grade 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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