Bcl-2 is Expressed in CLL Patients

1
Bcl-2 is Expressed in CLL Patients
ASchena et al. Blood 1992792981, BHanada et al.
Blood 1993151820, CRobertson et al. Leukemia
199610456, DZaja F, Leuk Lymphoma 199828567,
EAviram et al. Eur J Haematol 20006480,
FKlobusicka et al. Neoplasma 200249387,
GMenendez et al. Leukemia 200418491, HTracey
et al. J Pathology 2005206123
MA-9
2
Intracellular Uptake after Systemic Treatment
MA-19
Dai et al., Clin Cancer Res 2005112998
3
Suppression of Bcl-2 Correlates with
Intracellular Levels of Genasense
Bcl-2 mRNA ( of control)
Intracellular Genasense (pmol/mg protein)
Dose (µM)
K562 leukemia cell line, Dai et al. Clin Cancer
Res. 2005112998
MA-22
4
Down Regulation of Bcl-2 in AML Patient Marrow
70
60
50
Bcl-2 to Actin Ratio (chemiluminescence)
40
30
20
10
0
0
5
11
28
Time (days)
Genasense 7 mg/kg/d qdx10 CIVI, Marcucci et al.
Blood 2003 15425
MA-23
5
Down Regulation of Bcl-2 by GenasensePBMC from
Pediatric Solid Tumor Patients
Rheingold S et al., in preparation, M. Hogarty
laboratory, COG-ADVL0211 Study
MA-24
6
Age Impact on Response Overall
lt75 year old (N214) n () gt 75 year old (N27) n ()
CRnPRPR, n 95 (44.4) 8 (29.6)
CRnPR, n 26 (12) 2 (7)
7
Age Impact on Response by Arm
GFC GFC FC FC
lt 75 (N103) n () 75 (N17) n () lt 75 (N111) n () 75 (N10) n ()
CR/nPR/PR 45 (44) 4 (24) 50 (45) 4 (40)
CR/nPR 18 (18) 2 (12) 8 (7) 0
8
Reasons for Response Rate Difference in Study
GL303

• Randomized
• Multicenter
• Blinded histopathologic review
• Blinded clinical review
• More heavily pretreated ( 4 prior regimens)
  (29 vs 9)
• More Fludarabine Refractory (59 vs. 31)
• CT/US scans used to determine response