HospitalClinic InService for Zevalin Radioimmunotherapy for NonHodgkins Lymphoma IDEC Pharmaceutical

1
Hospital/Clinic In-Service for Zevalin
Radioimmunotherapy forNon-Hodgkins
LymphomaIDEC Pharmaceuticals Corporation
2
Zevalin Radioimmunotherapy ofNon-Hodgkins
Lymphoma

• Objectives
• Describe the incidence and prevalence of
  non-Hodgkins Lymphoma (NHL) in the US
• Explain the characteristics of radionuclides used
  in Zevalin radioimmunotherapy
• Describe the timeline for the Zevalin treatment

3
Zevalin Radioimmunotherapy ofNon-Hodgkins
Lymphoma

• Objectives (continued)
• Explain steps necessary to get started
• Describe the process for deriving dose calibrator
  calibration settings for Y-90
• Describe infusion techniques for Zevalin
• List acquisition parameters for imaging following
  injection of In-111 Zevalin

4
Non-Hodgkins Lymphoma

• Incidence 55,000/year and increasing
• Prevalence 300,000 cases
• Low-grade
• Advanced stages incurable
• Median survival 6.2 years
• Intermediate-grade
• Approximately 40 curable
• Median survival 2.2 years
• Most are B cell and express CD20

5

• CD20 antigen
• Expressed onlyon B-lineage cells
• Important for cellcycle initiation and
  differentiation
• Does not shed,internalize or modulate

CD20 antigen
B cell
Ibritumomab
Tiuxetan
Y-90

• Zevalin
• Ibritumomab
• Tiuxetan (MX-DTPA) conjugatedto antibody forming
  strongurea-type bond
• Stable retention of Y-90 or In-111

Y-90 or In-111 Zevalin
6
Y-90 Zevalin Treatment Schema

• Outpatient Treatment
• Day 1 Rituximab (250 mg/m2) 4 hour infusion
  In-111 Zevalin (5 mCi)
• Day 7, 8, or 9 Rituximab (250 mg/m2) 4 hour
  infusion Y-90 Zevalin (0.4 or 0.3 mCi/kgmax 32
  mCi)

7
Zevalin Radioimmunotherapy Treatment Schedule
Imaging dose
Therapeutic dose
Rituxan 250 mg/m2
Followed by In-111 Zevalin 5 mCi
or
or
Day
1
2
3
4
5
6
7
8
9
Scans
90120 hours (optional)
224 hours
4872 hours
0.4 mCi/kg in patients with a platelet count
?150,000/?L or 0.3 mCi/kg with a platelet count
100,000 - 149,000/?L.
8
Zevalin Tx Requires Coordinated Teamwork for a
Successful Tx
Radionuclide(s) Mallinckrodt or Amersham
Health In-111
IDEC Customer Service (ICS) Zevalin Cold Kit(s)
Radionuclide (ICS) MDS Nordion Y-90
Nuclear Pharmacy
Oncology
PATIENT

• Rituxan Rx
• Rituxan infusion(s)
• Zevalin Rx

• Zevalin Rx supplies
• Zevalin compounding
• Zevalin QC assessment
• Zevalin unit-dose distribution

Nuclear Medicine

• Zevalin patient scheduling coordination
• Zevalin administration(s)
• Zevalin imaging

9
Zevalin Therapy and Nuclear Medicine How to Get
Started

• Equipment and supplies
• Radiopharmaceutical characteristics
• Dose calibrator qualification
• Zevalin handling and administration
• Storage of unit-dose
• Calculation of patient dose
• Injection procedure
• Data Acquisition
• Imaging protocol
• Expected biodistribution
• Altered biodistribution
• Safety considerations

10
Equipment and Supplies

• Equipment
• Dose calibrator
• Must be geometrically qualified to calibrate
  multiple volumes of Y-90 Zevalin
• Dual/Single head gamma camera system
• Medium energy collimator(s)
• Infusion pump (optional)
• Must accommodate a 10 mL syringe and a 10 minute
  infusion time
• GM meter with pancake probe

11
Equipment and Supplies (continued)

• Syringe Shield
• Lead In-111
• Plastic/acrylic Y-90
• Unit dose
• In-111 Zevalin
• Y-90 Zevalin
• 0.22 micron low protein binding filter
• Absorbent paper

• Injection Supplies
• IV tubing with injection port
• 250 mL 0.9 normal saline
• Butterfly needle or angiocath
• Waterproof gloves
• Alcohol prep pads
• 2 x 2 gauze pads
• Three-stopcock

12
Radiopharmaceutical Characteristics

• Indium-111 Chloride
• APPROVED MANUFACTURER(S) Amersham Health or
  Mallinckrodt
• DAYS OF USE MON, TUES, or WED
• HALF-LIFE 67.3 hours
• ENERGY 171 and 245 keV
• DECAY Electron capture

• Yttrium-90 Chloride
• APPROVED MANUFACTURER only MDS Nordion
• DAYS OF USE TUES or WED
• Same day delivery
• HALF-LIFE 64.1 hours
• ENERGY 2.281 MeV
• DECAY Beta minus

13
ZevalinDose Calibrator Qualification
14
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use

• Discussion
• Most dose calibrators were designed to assay
  gamma emissions
• Y-90 is a pure beta emitter
• Bremmstralung emitted by Y-90 is the energy that
  can be assayed in most dose calibrators
• To accurately assay Y-90 in the dose calibrator,
  it is recommended that the calibration settings
  for the dose calibrator be qualified and derived
  using MDS Nordion Y-90 and corrected for
  different geometries

15
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use

• Establish Dial Settings
• Use MDS Nordion Y-90
• Activity conc. from Product Data Sheet
• Based upon activity transferred into 10 mL
  syringe or vial
• Must qualify for full Zevalin volume range 1-10
  mL ( 4 mCi - 40 mCi)

• Equipment specific
• Qualification requires 1 mL syringe centering
  device
• 1 mL TB syringe with removable needle - TD VS TC
• 10 mL syringe surrogate for unit-dose from NP
• Re-qualify if equipment changes

16
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use
1 Locate Manual Setting Dial
Background Activity
2 Set Background Activity to Zero
00.00 mCi
Manual Setting Knob
3 Set Other Button dial to manufacturers
suggested setting for Y-90 (048 for
Capintec) with Manual Setting Dial
Other Button
17
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use
4 Draw 40 mCi Y-90 with 1 mL TB syringe
MDS Nordion Y-90 vial
1 mL TB syringe (BD 305310 26G 5/8)
5 Change needle on TB syringe
6 With Centering Device assay 1 mL syringe _at_
048 setting (starting dial setting for Capintec)
Lucite-shielded 1 mL TB syringe
18
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use
7 Change manual dial setting until 4.0 mCi
is displayed, multiply x 10
MDS Nordion Y-90 vial
8 Transfer 40 mCi to glass reaction vial and QS
to 10.0 mL total volume
9 To determine actual activity added to reaction
vial, assay residual activity left in 1 mL
syringe and subtract from 40 mCi
Lucite-shielded 1 mL TB syringe
Reaction vial with final conc. 4.0 mCi/mL
19
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use
10 Using 10 mL syringe, remove and assay
consecutive 1 mL aliquots from reaction vial and
assay until entire volume of Y-90 is in syringe
13 Use dial setting from table to plot graph for
slope
Reaction vial with final conc. 4.0 mCi/mL
11 Change manual dial setting at each aliquot to
equal calculated activity displayed on table,
multiply x 10
Assay 10 mL syringe or reaction vial
Lucite-shielded 10 mL syringe
12 Record dial setting at each volume- aliquot
on table
20
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use
Example Table A for 10 mL Syringe
21
Yttrium-90 Dose Calibrator Qualification for
Zevalin Use
Approximate Zevalin Volumes for 32 mCi - 16 mCi
22
ZevalinHandling and Administration
23
Zevalin Unit-Dose Storage Shelf-life

• Refrigerate Zevalin unit-dose (2 - 8 C) if not
  ready for immediate injection
• Shelf-life 12 hours for In-111 Zevalin after
  preparation
• Shelf-life 8 hours for Y-90 Zevalin after
  preparation

24
Calculate Patient Dose

• In-111 Zevalin imaging dose is 5 mCi
• Y-90 Zevalin therapy dose is based on patients
  actual baseline weight and platelet levels
• 0.3 mCi/kg Y-90 Zevalin - platelets 100,000 -
  149,000
• 0.4 mCi/kg Y-90 Zevalin - platelets gt 150,000
• NOTE Y-90 Zevalin dose must not exceed 32 mCi

25
Injected Activity Y-90 Zevalin

• Just prior to injection, assay the dose in the
  dose calibrator
• Determine the total volume of the dose from the
  unit-dose label
• Dial in the calibration number correlating to
  unit-dose volume for your dose calibrator
• For most dose calibrators, once the reading has
  stabilized, multiply the reading by a factor of
  10 to determine the unit-dose total activity
• Assay the residual activity in the syringe after
  injection to determine the total activity
  injected _at_ 1 mL setting

26
Zevalin Administration Equipment

• 10 mL syringe for 0.9 NS
• Low protein binding 0.22 micron filter
• Syringe shield (lucite plus other)
• Three-way stopcock
• 0.9 Normal Saline

27
Zevalin Administration

• Injecting Zevalin
• Establish venous access with butterfly needle or
  angiocath attached to IV tubing and 250 mL of
  0.9 normal saline bag
• Flush venous line with10 mL of 0.9 NaCl to
  reconfirm patency
• Stop flow from IV bag
• Place a 0.22 micron (low protein binding) filter
  between the 10 mL syringe containing the unit
  dose of Zevalin

28
Zevalin Administration (continued)

• Options for Injecting Zevalin
• SLOWLY inject Zevalin over 10 minutes
• Do not inject concomitantly with other IV
  solutions or medication
• Do not inject as an intravenous bolus
• Slowly flush line with at least 10 mL of 0.9
  NaCl after injection is completed

29
Zevalin Administration Equipment (continued)
30
Zevalin Administration Equipment (continued)
31
Zevalin Administration Equipment (continued)
32
Zevalin Administration Equipment (continued)
33
Zevalin Data Acquisition and Imaging
34
Data Acquisition for In-111 Zevalin

• Dual or single head gamma camera system
• Medium energy collimator(s)
• 172 and 247 keV with 15 window
• 256 x 1024 matrix
• Speed (dependent on time after injection)
• 10 cm/min (20 minute scan) at 2 - 24 hours
• 7 - 10 cm/min (30 minute scan) at 48 - 72 hours
• 5 - 7 cm/min (40 minute scan) at 90 - 120 hours
  (optional)

35
Data Acquisition for In-111 Zevalin

• Whole body scans (anterior and posterior views)
  will be acquired as follows
• 2 - 24 hours post injection
• 48 - 72 hours post injection
• 90 - 120 hours post injection (optional, pending
  results of the first two scans)

36
In-111 Zevalin Expected Biodistribution on Imaging

• Radioactivity in the blood pool on first image,
  less on second image
• High uptake in normal liver and spleen
• Low uptake in kidneys, urinary bladder, and bowel
• Tumor uptake visualized as areas of increased
  intensity
• Decision administer Y-90 Zevalin

37
In-111 Zevalin Altered Biodistribution on Imaging

• Blood pool not visualized on first image
• Lung uptake more intense than liver uptake on
  second image
• Kidney uptake greater than liver uptake on second
  image
• Diffuse intense uptake in bowel comparable to
  uptake in liver on second image
• Altered biodistribution is rare
• Do not administer Y-90 Zevalin

38
Median Y-90 Zevalin RadiationAbsorbed Doses to
Organs and Tumor