4. Bachy and Salles. Seminars in Hematology, Vol 52, No 2, April 2015

5. 55% Sehn et al. Blood 2007Coiffie et al. Blood 2010 Age +16 Newly diagnosed DLBCL Treated with R-CHOP Age 60-80 Newly diagnosed DLBCL Treated with CHOP vs R-CHOP 34 % 21%

6. 64% 29% Ozturk et al. Leukemia&Lymphoma 2015 67 % 44%

7. 92% 84% Recher et al. Lancet 2011Molina et al. JCO 2014 Frequent febrile neutropenia, secondary malignancy OS GCB OS non-GCB

8. A.O. Gang et al. Annals of Oncology 2012 A.O. Gang et al. Leuk&Lymp 2015

9. 68 DLBCL Age 18-75 IPI>2, aaIPI>1 Purroy et al. BJH 2014

10. Study group n CT protocolİnclusion critoutcome Italian Lymphoma Found Vitolo U Ann Oncol. 2011;22. abst 072 399R-CHOP+BEAM R-CHOP(8) aaIPI: HI,H2 year PFS (70 vs 59) P=0.0128 OS.NS SWOG.US/Canadian int Stiff PJ. NEJM 2013 397R-CHOP+HDT R-CHOP(8) aaIPI:HI,H2yr PFS 69 vs 56% P=0.02 Schmitz N.GHNHL Lancet Oncol 2012 230R-CHOEPX8 R-mCHOEP(4)+OKIT aaIPI:HI,H3yrOS 84.6vs 77% p:=Sign aaIPI:2 GOELAM 075 Le GouilleS. JCO.2011;29,abstr 8003 340R-CHOP14X8 2XR-CHOP+Mtx+ ARA-C+HDT aaIPI1-2+bulky aaIPI 3-4 OS%83 NS

11. IPI2 years PFS % (SCT vs Standard)2 years OS % (SCT vs Standart) H-I66 vs 6370 vs 75 High75 vs 4182 vs 64 p0.02NS

12. Outside of clinical trials first line chemotherapy with stem cell support is not reccomended

14. OBJECTIVES To determine the effect of iPET guided therapy on the outcome of aggressive lymphomas Between 2007-2012, age range 18-80 926 aggressive lymphoma patients recruited from 57 oncological centers and iPETs analyzed in 23 nuclear imaging centers 757 CD20+ lymphomas (DLBCL, mediastinal B cell, grade 3 Follicular lymphoma) 13 CD20- lymphomas 83 peripheralT cell lymphomas METHODS Treatment decided according to the iPET result following the second cycle of R-CHOP iPET evaluated 3 weeks after 2nd R-CHOP (to avoid inflammatory reactions) No G-CSF after 2nd R-CHOP (to avoid altered glucose biodistribution) Objective evaluation regarding Standardized Uptake Value (SUV) Favorable response defined as >66% decrease in maximum SUV

15. Initial treatment: 2 R-CHOP Favorable iPET (n=746) Unfavorable iPET (n= 107) 4 R-CHOP + 2 R 6 R-CHOP 6 cycle of more complex and intensive treatment (Burkitt Protocol) P A R T A PARTBPARTB RANDOMIZATION 853 patients of 926 were evaluable in the intend to treat population at a median follow- up of 33 months No beneficial effect on Treatment Failure, CR rate and, Overall Survival in the unfavorable group switched from R-CHOP to Burkitt protocol Burkitt protocol associated with more severe Grade ¾ Leukopenia (p=0.043) Thrombocytopenia (p=0.007) Mucositis (p=0.002)

16. High Level of gene expression Low Genes Rosenwald A et al. N Engl J Med. 2002;346:1937-1947.

17. Slide 11 Presented By David Scott at 2015 ASCO Annual Meeting

18. Cell-of-origin – a scaffold Presented By David Scott at 2015 ASCO Annual Meeting

19. Slide 44 Presented By David Scott at 2015 ASCO Annual Meeting

24. Younes et al. Lancet oncology 2014

30. Vitolo et al. Lancet Ocol 2014 Nowakowski et al. JCO 2015