AMD3100 Combined with Standard Doses of GCSF Leads to Rapid, Consistent Mobilization of Hematopoieti

1
AMD3100 Combined with Standard Doses of G-CSF
Leads to Rapid, Consistent Mobilization of
Hematopoietic Progenitor Cells in Patients with
Non-Hodgkin's Lymphoma (NHL) and Multiple
Myeloma.
Dr. Ivana Micallef, Assistant Professor of
Medicine, Mayo Clinic College of Medicine,
Rochester, Minnesota
ASH 2004, December 3-7, 2004 in San Diego, CA
2
Study Objectives

• To determine if AMD3100 along with G-CSF used to
  mobilize stem cells is safe
• To determine if AMD3100 will lead to a gt 2 fold
  increase in the number of circulating CD34 cells
  mobilized by G-CSF in patients with myeloma and
  NHL
• To determine if CD34 stem cells mobilized by the
  combination of G-CSF and AMD3100 and transplanted
  into patients with myeloma and NHL will lead to
  ANC engraftment by day 12, and platelet
  engraftment by day 21

3
Study Design
4
Treatment Plan

• Mobilization with G-CSF and AMD3100
• G-CSF 10?g/kg/day SQ with apheresis
  starting D5 until 5x106 CD34/kg are
  collected or a maximum
  of 9 days
• and
• AMD3100 240?g/kg/day SQ starting evening of D4
  (10- 11hrs pre- 1st apheresis) and
  daily at the same time until
  5x106 CD34/kg are collected for a
  maximum of 5 doses
• Apheresis of patients begins on the 5th day of
  G-CSF and continues daily until 5x106 CD34/kg are
  collected or to a maximum of 5 aphereses
• Peripheral blood CD34/?l are assayed nightly
  pre-AMD3100 (10 hours pre-apheresis) and
  immediately pre-apheresis, as well as from
  apheresis product daily
• Preparative regimen per local practice
• Stem cell infusion and G-CSF used
  post-transplant per local practice

5
Analyses Performed

• Peripheral blood CD34 before and after AMD3100
• CD34/kg mobilized by this novel combination
• CD34/kg mobilized in heavily pre-treated
  patients defined as
• gt 10 cycles of chemotherapy
• platinum based salvage therapy
• radiotherapy to marrow bearing sites
• Engraftment times
• Adverse events due to study drug

6
Patient Demographics (N34)
7
Increase of CD34/?l of Blood Pre/Post First Dose
of AMD3100
Median
Median
CD34/µL
CD34/µL
Median
Pre AMD
Post AMD
Fold
Dose 1
Dose 1
Increase
All patients (N35)
21
52
2.6
Patients who
6
achieved
gt
5x10
56
124
2.4
CD34/kg in single
apheresis (N8)
Patients who did not
reach endpoint of
gt

5.5
14
2.6
6
5x10
CD34/kg (N6)

• AMD3100 increased the number of circulating
  CD34/?l in the peripheral blood by 2.6 fold in
  patients with myeloma and NHL being mobilized
  with G-CSF

8
Apheresis Data (N31)
6
Target Endpoint
gt5x10
CD34/kg
Achieving Endpoint
24 (77)
6
31 (100)
Reaching 2x10
CD34/kg
6
29 (94)
Reaching 4x10
CD34/kg
6
2
Median of apheresis to reach 5x10
CD34/kg
Median of apheresis done in study
2
Median cell dose collected
6
5.72x10
CD34/kg
CD34 yield for patients with lt10 CD34/ pre-
6
4.5x10
CD34/kg
AMD3100 (N7)
CD34 yield for heavily pre-treated (N9)
6
5.4x10
CD34/kg
CD34 yield for non-heavily pretreated (N12)
6
7.4x10
CD34/kg

• All patients had 2x106 CD34/kg collected, and
  81 met the 5x106 CD34/kg endpoint, included 5/9
  heavily pre-treated patients

9
Engraftment Data

• Engraftment of neutrophils and platelets was
  rapid. ANC11 days platelets13days

ANC
Platelets
gt500/mL
gt20,000/mL
All patients (N30)
11 (8-13)
13 (7-30)
Heavily pre-treated
11 (8-11)
13 (8-30)
(N11)
Non-heavily pre-
11 (9-13)
14 (9-26)
treated (N8)
10
Safety Data

• Most Frequently Reported AEs Considered Related
  to Study Drug in gt 10 (N29)

11
Conclusions

• AMD3100 increased the number of circulating
  CD34/?l in the peripheral blood in patients with
  myeloma and NHL being mobilized with G-CSF by 2.6
  fold.
• All patients had 2x106 CD34/kg collected, and
  81 met the gt5x106 CD34/kg endpoint, included
  5/9 heavily pre-treated patients.
• Engraftment of neutrophils and platelets was
  rapid time to ANC11 days platelets13 days
• AEs considered related to study drug were
  gastrointestinal (48), particularly mild
  diarrhea (28) and injection site erythema (17)
• This new novel combination appears promising to
  mobilize greater numbers of stem cells, even in
  heavily pre-treated patients. It may replace
  both G-CSF and chemotherapy G-CSF stem cell
  mobilization.