Zoledronic Acid and Pamidronate in Breast Cancer

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(No Transcript)
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Overview

• Identify the diagnostic criteria for multiple
  myeloma
• Compare first second line therapies, using data
  from clinical trials
• Describe adjunctive supportive therapies

3
Multiple Myeloma

• Plasma cell malignancy
• Second most common hematologic malignancy
• Characterized by monoclonal immunoglobulin
• MGUS
• Smoldering MM
• Amyloidosis

4
MM Epidemiology

• 19,900 new cases per yr, 50,000 total cases, 2
  cancer deaths in U.S.
• Higher incidence in African Americans, Pacific
  Islanders
• Median age 71 yrs
• Exposure to radiation, petroleum products,
  pesticides Agent Orange

Greenlee RT. CA Cancer J Clin 20015115.
Bergsagel DE. Blood 1999941174
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Presenting Features

• Bone disease hypercalcemia
• Recurrent infections
• Anemia and fatigue
• Renal failure due to multiple causes
• Neuropathy
• Asymptomatic in a minority of the patients

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Signs Symptoms in 1027 Newly Diagnosed Myeloma
Patients
Kyle RA. Mayo Clin Proc 20037821-33
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Criteria for Diagnosis

• Active MM
• ?10 PC
• M spike
• AND

• MGUS
• lt3 g M spike
• lt10 PC
• AND

• Smoldering MM
• ?3 g M spike
• OR ?10 PC

Anemia, bone lesions, high calcium or abnormal
kidney function
No anemia, bone lesions normal calcium and
kidney function
Kyle RA. N Engl J Med 2002 346 564
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Myeloma Prognostic Factors

• Serum ?2 microglobulin
• Cytogenetics - del13 or 13q-, t(414), 17p-,
  hypodiploid
• C-reactive protein
• LDH
• Plasmablastic morphology
• Peripheral blood plasma cells
• Gene expression profile

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Incidence of Chromosomal Abnormalities in MM

• n 1064 patients
• Chromosomal changes observed in 90 of patients

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International Staging System (ISS) for
Symptomatic Myeloma
ß2m lt 3.5 mg/L and albumin lt 3.5 g/dL or ß2m
3.5 - lt 5.5 mg/L, any albumin
Greipp et al. J Clin Oncol 2005 23 3412-20
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Initial Diagnostic Evaluation

• Hx and physical examination
• Blood work-up
• CBC with diff and platelet counts
• BUN, Creatinine
• Calcium, albumin
• Serum protein electrophoresis (SPEP) and
  immunofixation
• Quantitative immunoglobulins
• Serum free lyte chains
• ?2-microglobulin

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Initial Diagnostic Evaluation

• Urine
• Bence Jones quantitation
• 24-hr protein electrophoresis (UPEP) and
  immunofixation
• Other
• Skeletal survey
• Unilateral bone marrow aspirate and biopsy for
  histology, cytogenetics and FISH

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Serum Protein Electrophoresis
Monoclonal Protein in Myeloma
Normal
Kyle RA and Rajkumar SV. Cecil Textbook of
Medicine, 22nd Edition, 2004
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Immunofixation to Determine Type of Monoclonal
Protein
IgG kappa M protein
Lambda Light Chains
Kyle RA and Rajkumar SV. Cecil Textbook of
Medicine, 22nd Edition, 2004
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Distribution of Monoclonal Proteins

• M protein found in serum or urine or both at time
  of diagnosis 97
• Serum M spike by protein electrophoresis 80
• Abnormal serum immunofixation 93
• Abnormal urine immunofixation 75
• Non-secretory myeloma 3

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Malignant Plasma Cells in Marrow
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Bone Involvement in Different Tumor Types
1. National Cancer Institute. Available at
http//seer.cancer.gov/csr/1973-1999/prevalence.pd
f. Accessed 1/27/2005. 2. Coleman RE.
Oncologist. 20049(suppl 4)14-27. 3. Kyle RA et
al. Mayo Clin Proc. 200378 21-33. 4. Smith W
et al. Semin Oncol. 200431(suppl 4)11-15. 5.
Lipton A. J Support Oncol. 20042205-213. 6. Tu
S-M, Lin S-H. Cancer Treat Res. 200411823-46.
7. Palumbo A et al. Blood. 20041043052-3057.
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Bone Imaging in MM

• Skeletal radiography is the primary diagnostic
  test to detect destructive bony lesions in
  multiple myeloma
• MRI is useful in assessing whether spinal
  compression fractures are due to a focal mass or
  from osteopenia due to increased osteolysis
• PET scans can be used to detect soft tissue or
  bone metastases

Angtuaco EJ et al. Radiology. 200423111-23.
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Bone Scans in Myeloma Can Underestimate Bone
Involvement
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Bone Cell Stimulation in Malignancy
Osteoclasts
Osteoblasts
Multiple myeloma
Osteolytic solid tumors including breast cancer
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• Initial Approach to Treatment

Clearly not a transplant candidate
Potential transplant candidate
Can include melphalan- based combinations
Non-alkylator based induction
Stem cell harvest
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Thalidomide in Myeloma

• 63 response when combined with Dex versus 41 to
  Dex as initial therapy (FDA approved May 2006)
• Does not compromise subsequent PBSC mobilization
  and collection

Barlogie et al. Blood 200198 492.
Anagnostopoulos et al. Brit J Hematol
2003121768. Rajkumar et al. J Clin Oncol 2006
24431-6. Palumbo et al. Blood 104(Suppl) 63a,
2004.
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SWOG S0232 Dex vs Lenalidomide/Dex in
Newly-diagnosed MM
RANDOMI ZAT ION
Dex 40 mg/d po, days 1-4, 9-12, 17-20
Lenalidomide 25 mg/day po, days 121 Dex 40 mg/d
po, days 1-4, 9-12, 17-20
Zonder et al Abstract LBA8025
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Lenalidomide/Dex (LD) vs Dex (D) Interim
Analysis of Response, PFS OS
LD (n61 evaluable for response) D (n72
evaluable for response)
Response,
P0.001
Zonder JA et al. Presented at 49th ASH Annual
Meeting December 811, 2007 Atlanta, GA
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EA403 Lenalidomide with High vs. Low-dose Dex in
Newly-diagnosed MM
RANDOMI ZAT ION
High-dose dex
Lenalidomide 25 mg/day po, days 1-21 Dex 40 mg/d
po, days 1-4, 9-12, 17-20
Low-dose dex
Lenalidomide 25 mg/day po, days 1-21 Dex 40 mg/d
po, once weekly
Rajkumar et al. Abstract 74. ASH Annual Meeting
December 8-11, 2007, Atlanta, GA
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Lenalidomide with High vs. Low-dose Dex in
Newly-diagnosed MM Serious AEs ( 3)
LLenalidomide DStandard-dose dexamethasone
dLow-dose dexamethasone Fishers exact
Rajkumar SV et al. Presented at 49th ASH Annual
Meeting December 811, 2007 Atlanta, GA
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Lenalidomide with High vs. Low-dose Dex Overall
Survival
Rev/low dose dex
Rev/high dose dex
Probability
Time in months
Rajkumar et al. Blood 2007110(11) abstract 74
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IFM 2005-01 Bortezomib/Dex vs VAD as Induction
Treatment in MM
N482Untreated MM age 65 yr
VAD 4
Bort/Dex 4
Induction
Melphalan 200 mg/m2 ASCT
Melphalan 200 mg/m2 ASCT
Transplant 1
Second ASCT or RIC allo if ltVGPR
Harousseau J-L et al. Presented at 49th ASH
Annual Meeting December 811, 2007 Atlanta, GA
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Bortezomib/Dex vs VAD Response
Response to Induction
Response Post ASCT
Harousseau JL, et al. Ash 2007, abstract 450
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Bortezomib-Thalidomide-Dex vs. Thal-Dex in Newly
Diagnosed MM
Bortezomib 1.3mg/m2 D 1, 4, 8,
11 Thalidomide 200mg/day Dex 40mg/d PO
D 1-2, 4-5, 8-9, 11-12 (n129)
Newly diagnosed MM (n256)
PBSC harvest ASCT x 2 with MEL-200
Thalidomide 200mg/day Dex 40mg/day PO D 1-4,
8-12 (n127)
Patients randomized to LMWH (40mg/day), ASA
(100mg/day) or warfarin (1.25mg/day)
Cavo et al. Blood 2007 110(11)abstract 73
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Bortezomib-Thalidomide-Dex
vs. Thal-Dex
Response to Induction
Response Post ASCT
Cavo et al. Blood 2007 110(11)abstract 73
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Lenalidomide/Bortezomib/Dex for Patients with
Newly Diagnosed MM
Decks, 40 mg/day D 1, 2, 4, 5, 8, 9, 11 and 12
20 mg, cycles 58 Amended to 20mg/10mg cycles
1-4/5-8 based on safety data
Richardson et al. Blood 2007 110(11)abstract
187
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Lenalidomide/Bortezomib/Dex Response

• Best response n 42 evaluable pts
• CR/nCR 29
• VGPR 52
• PR 98

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Initial Therapy Considerations

• Ensure patient does not have smoldering
  (asymptomatic) MM
• Approach to therapy is based on whether a pt is a
  transplant candidate
• Consider clinical trials if available
• Improving complete response rates is a key goal
  of current trials

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Therapy Options NonTransplant Candidate

• Melphalan Prednisone (MP)
• Melphalan Prednisone Thalidomide (MPT)
• Dexamethasone (Dex)
• Thalidomide Dexamethasone (Thal/Dex)
• Lenolidomide Dexamethasone (Rev/Dex)
• Bortezomib /- Dexamethasone (Vel/Dex)

NCCN Practice Guideline-v.2.2008
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Melphalan Prednisone

• Response rate 40
• Duration of response 18 month
• Overall survival 24-36 months
• Cycle is repeated every 4-6 weeks

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MP vs. MPT Randomized Studies

• Study Age (yrs) Regimen
• Palumbo et al gt 65 MP vs MPT
• Facon et al gt 65 MP vs MPT vs Mel100x2
• Hulin et al gt 75 MP vs MPT

Palumbo et al. Lancet 2006 367825-41. Palumbo
et al. Blood 2008 May 27. Facon et al. Lancet
20073701209-18. Hulin et al. Blood 200711083
Abstract 75.
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Summary of MP-Thalidomide Trials
Palumbo et al. Lancet 2006 367825-41. Palumbo
et al. Blood 2008 May 27. Facon et al. Lancet
20073701209-18. Hulin et al. Blood 200711083
Abstract 75.
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VMP vs MP in Previously Untreated MM Patients
(VISTA)
R A N D O M I Z E
MP
9 x 6-week cycles (54 weeks) in both arms
VMP

• 65 yrs or lt65 yrs and not transplant-eligible
  KPS 60
• Primary Endpoint TTP
• Secondary Endpoints CR, ORR, TRR, DOR, PFS, TNT,
  OS, QoL

San Miguel, et al. Blood. 200711078a, abstract
76
40
VMP vs MP Response to Treatment
ORRobjective response rates CRcomplete
response, immunofixation-negative
measured in serum and/or urine by central
laboratory
San Miguel, et al. Blood. 200711078a, abstract
76. Bladé et al. Br J Haematol 19981021115
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Salvage Therapy

• Thalidomide-Dexamethasone
• Lenalidomide-Dexamethasone
• Bortezomib /- Dexamethasone
• Pegylated-Liposomal Doxorubicin (PLD)- based
  regimens

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Thalidomide in Relapse MM

• PR in 30 relapsed and/or refractory MM
• 47 response when combined with Dex
• No advantage of any dose gt200 mg/day
• Toxicities sedation, constipation, peripheral
  neuropathies and VTE

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Lenalidomide (Revlimid)

• More potent immunomodulator than thalidomide
• SE myelosuppression
• Only available through RevAssist Distribution
  Program
• Monitor CBCs weekly for first 8 wks
• Increase risk of VTE (DVT and PE)

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2 Phase Trials Lenalidomide/Dex in Relapsed or
Refractory MM

• North American study MM-009
• European study MM-010
• Dose 25mg days 1-21
• Dex 40mg days 1-4, 9-12, 17-20 x 4 courses
• Primary endpoint TTP
• Secondary endpoints OS, RR, safety, first SRE, PS

Dimopoulos et al. N Engl J Med 2007 3572123-32.
Weber et al. N Engl J Med 2007 3572133-42.
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Response Dex vs. Len-Dex
80
(gt50)
PR
61.2
60
59
CR (gt20)
Response Rate ()
plt0.001
40
34.7
22.8
24
20
44
18.7
20.6
26.5
15
4.1
3.4
0
Len/dex
Len/dex
Dex
Dex
009
010
009
010
Weber D. ASCO 2005 Dimopoulos Blood
2005106abstract 6
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Grade 3-4 Toxicity Results MM-009 Trial
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VTE Prevention with Immunomodulating Agents

• As single agents minimal risk prophylaxis may
  be considered
• Concomitant chemotherapy especially dex,
  anthracyclines ESAs, increase risk as much as
  58
• Low-dose warfarin not protective
• ASA adequate in lower risk patients receiving
  dex an immunomodulator
• LMWH (enoxaparin 40mg QD), full dose warfarin,
  are recommended for patients at high risk for VTE

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Bortezomib (Velcade)

• Reversible inhibitor of chymotrypsin-like
  activity of 26-S proteasome
• Prevents proteolysis of ubiquitinated proteins
  can lead to apoptosis of tumor cells
• Dosing 1.3 mg/m2 IV bolus d 1, 4, 8, 11 (21-d
  treatment cycle) for a maximum of 8 cycles
• FDA approved for MM that has relapsed after 1
  prior standard therapies

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Bortezomib vs. HDD in Relapse MM Apex Trial

• International trial, 93 sites
• Pts had to receive 1-3 prior therapies
• Dex-refractory excluded
• Induction therapy
• 1.3mg/m2 IV days day 1, 4, 8, 11 x eight 3-wk
  cycles vs Dex 40mg PO 1-4, 9-12, 17-20 x four
  5-wk cycles
• Maintenance therapy
• 1.3mg/m2 IV days 1, 8, 15, 22 x three 5-wk cycles
  vs Dex 40mg PO day 1-4 x five 5-wk cycles

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Results APEX Trial
TTP Times to Progression CR (IF-) Complete
response, immunofixation negative PR (combined
complete and partial response rates)
Richardson et al. N Engl J Med 20053522487-98
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Adverse Events APEX Trial
Plt 0.001
Richardson et al. N Engl J Med 20053522487-98
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Pegylated Liposomal Doxorubicin Bortezomib

• Combination
• Significant increase in TTP
• 45 risk reduction of recurrence
• No significant change in ORR
• Increase in grade III-IV toxicities seen in
  combination group (64 vs. 80) mostly due to
  myelosuppression
• High PLD discontinuation rate secondary to AE
  (36)

Orlowski et al. J Clin Oncol. 2007
253892-3901
53
Treatment Options-Relapsed Patient

• Since no therapy is curative, all options need to
  be tried sequentially
• No good data on optimum sequence or regimen
• All patients should be encouraged to participate
  in ongoing clinical trials
• Cumulative toxicities from prior therapies may
  influence decision

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Treatment of Bone Disease

• Bisphosphonates
• Surgical procedures
• Vertebroplasty
• Balloon Kyphoplasty
• Radiotherapy
• Treatment of myeloma

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ASCO Guidelines for TreatingBone Loss in
Multiple Myeloma
MM patients with lytic disease or osteopenia on
plain radiographs or imaging studies
Intravenous pamidronate 90 mg deliver over at
least 2 hrs or zoledronic acid 4 mg over 15
minutes every 3 to 4 weeks.
Continue therapy for 2 yrs consider stopping in
patients w/ responsive or stable disease further
use at physicians discretion
Kyle RA et al. J Clin Oncol. 2007252464-72.
56
Pamidronate in Multiple Myeloma
21-month data. Berenson JR et al. J Clin Oncol.
199816593-602.
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Issues with BP Therapy

• Renal toxicity
• Osteonecrosis of the jaw
• Decreases skeletal events by 50 patients still
  progress but at a slower rate
• No clear anti-tumor activity

58
Renal Toxicity Pamidronate Zoledronic Acid
Adapted with permission from Berenson JR.
Oncologist. 20051052-62.
59
Osteonecrosis of the Jaw

• Features of Suspected ONJ
• Exposed bone in maxillofacial area associated
  with dental surgery or occurs spontaneously, with
  no evidence of healing
• Working Diagnosis of ONJ
• No evidence of healing after 8 weeks of
  appropriate dental care
• No evidence of metastatic disease in the jaw or
  osteoradionecrosis

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Anemia Treatment Goals

• Treat the underlying malignancy
• Decrease fatigue
• Decrease need for PRBC transfusions
• Treat the patient, not the number

61
2007 ASCO Practice Guidelines for ESA

• General
• Review peripheral smear consider iron, folate,
  and B12 deficiency as potential causes for
  anemia, assess for occult blood loss.
• Comparative effectiveness
• Agents are considered equivalent in terms of
  safety and efficacy
• No reason to believe that a patient who fails to
  respond to one ESA will have a response to a
  different ESA

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Myeloma Features Unique to VA Patient Population

• Agent Orange and radiation exposure
• Minority population
• Older patients
• Co-morbidities
• Larger number unable to undergo transplantation
• Social issues nursing home and rehab facilities

63
Myeloma Initiative at VA (MIVA)

• Investigator-driven effort for multi-VA clinical
  research
• Patients get access to the most advanced therapy
• Provides proof of efficacy of therapy
• Allows VA to participate in new drug development
• Patient education program
• Tablet PCs
• Provider education program

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VANTS Call

• July 15, 2008, 2 pm ET
• August 26, 2008, 2 pm ET
• 1-800-767-1750
• Access code 86360

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Supplement Slides
66
Criteria for Diagnosis

• Symptomatic Myeloma
• Anemia
• Bone lesions
• Hypercalcemia
• Renal dysfunction

Durie BGM. Sem Oncol 198613300
67
Criteria for Diagnosis

• Plasmacytomas on tissue biopsy
• Bone marrow plasmacytosis (gt30 plasma cells)
• Monoclonal immunoglobulin spike on serum
  electrophoresis
• IgGgt3.5 g/dl or IgA gt2.0 g/dl
• kappa or lambda light-chain excretion gt1.0 g/day
  on 24-hr urine protein electrophoresis

Durie BGM. Sem Oncol 198613300
68
MM Chromosomal Alterations

• 14q32 majority of cases
• 11q13 most common (bcl-1 locus, 30)
• 4p16 (FGFR3, MMSET, 25)
• 8q24 (c-myc, 5)
• 16q23 (c-maf, 1)
• 6p25 (IRF4, rare)
• 13 deletion (Rb) 10-20 of patients using
  conventional cytogenetics and 50 using FISH

Kuehl WM, Bergsagel PL. Nat Rev Cancer. 20022175
69
Positron-Emission Tomography

• Visualizes the uptake of positron-emitting
  radiopharmaceuticals by tissues
• Can be used to detect soft tissue or bone
  metastases
• Can be useful in distinguishing benign and
  malignant bone lesions
• May be more sensitive for detecting osteolytic
  metastases than osteoblastic metastases
• Disadvantages include high cost, small lesions
  may not be detected, false positives from
  inflammatory lesions

Hamaoka T et al. J Clin Oncol. 2004222942-2953.
70
One-year Survival Rate in Phase III Newly
Diagnosed MM Trials
intent to treat population 80 age lt65
71
Thal-Dex vs. Dexamethasone

• Randomized trial in 207 pts with newly diagnosed,
  symptomatic MM
• Thalidomide (200mg/day) dexamethasone (40mg
  daily days 1-4, 9-12, 17-21) to
  placebo-dexamethasone (same schedule)
• Primary endpoint at 4 months best documented
  response and toxicity

Rajkumar et al. JCO 2006 24 431-6
72
Results
Rajkumar et al. JCO 2006 24 431-6
73
Thal/Dex Best Response Within 4 Cycles
Based on ITT, 50 reduction in serum and urine
M protein, or 90 reduction in Urine M protein
if only urinary protein was evaluable for
response Allowing for use of serum M protein
when a measurable urine M protein was unavailable
at follow-up
Rajkumar SV, et al. J Clin Oncol., 200624431
74
E4A03 Serious AEs (3)
LLenalidomide DStandard-dose dexamethasone
dLow-dose dexamethasone Fishers exact
Rajkumar SV et al. Presented at 49th ASH Annual
Meeting December 811, 2007 Atlanta, GA
75
Thalidomide in Myeloma

• MPT increases overall and extent of response, as
  well as prolongs PFS and OS compared to MP and
  MEL 100 x2 as initial therapy of elderly patients
  

Barlogie et al. Blood 98 492, 2001
Anagnostopoulos et al. Brit J Hematol 121768,
2003. Rajkumar et al. J Clin Oncol 2005, in
press. Palumbo et al. Blood 104(Suppl) 63a, 2004.
76
MP vs. MPT Results

• Response rates
• Complete response 2 vs. 15
• Partial response 45 vs. 60
• MR 17 vs. 5
• No response 15 vs. 5
• PD 17 vs. 8
• Survival
• 2 yr EFS 27 vs. 54
• 3 yr OS 64 vs. 80

Lancet. 2006 367 825-31
77
Results Dex vs. Len-Dex
N Eng J Med 2007 3572123-32, N Eng J Med 2007
3572133-42
78
VMP vs MP in previously untreated MM patients
(VISTA)
65 yrs or lt65 yrs and not transplant-eligible
KPS 60
VMP Cycles 1-4 Bortezomib 1.3 mg/m2 IV days
1,4,8,11,22,25,29,32 Melphalan 9 mg/m2 and
prednisone 60 mg/m2 days 1-4 Cycles
5-9 Bortezomib 1.3 mg/m2 IV days
1,8,22,29 Melphalan 9 mg/m2 and prednisone 60
mg/m2 days 1-4
R A N D O M I Z E
9 x 6-week cycles (54 weeks) in both arms
MP Cycles 1-9 Melphalan 9 mg/m2 and prednisone 60
mg/m2 days 1-4
Primary Endpoint TTP Secondary Endpoints CR,
ORR, TRR, DOR, PFS, TNT, OS, QoL
San Miguel, et al. Blood. 200710878a, abstract
76
79
VMP vs MP Grade 34 Adverse Events
Patients

• Transfusion (26 vs 35) and EPO support (34 vs
  42) somewhat lower on VMP arm
• PN resolved or improved in 75 of cases in a
  median of 64 days
• DVT was low and the same on both arms (1)

San Miguel, et al. Blood. 200710878a, abstract
76
80
Pegylated-Liposomal Doxorubicin (PLD)

• A liposomal (lipid) based formulation of
  doxorubicin
• FDA approved in progressive/recurrent ovarian
  cancer, AIDS-related Kaposi sarcoma, locally
  advanced or metastatic breast cancer, and MM
• Advantage decreased toxicity in particular,
  myelosuppression and cardiac toxicity
• Studied in a variety of combinations for MM
  including bortezomib, lenalidomide, thalidomide
  and melphalan

81
PLD Bortezomib

• Phase III, RC, open-label international trial
  comparing efficacy and safety of PLD bortezomib
  to bortezomib in relapsed or refractory myeloma
• 646 patients from 123 centers enrolled
• gt 2/3 of patients received 2 previous therapies
• Dosing bortezomib 1.3 mg/m2 IVP days 1,4,8
  11 (standard dosing).
• PLD 30 mg/m2 IVPB on day 4

Orlowski et al. J Clin Oncol. 2007 253892-3901
82
Results
Orlowski et al. J Clin Oncol. 2007 253892-3901
83
Doxorubicin Selected Toxicities Patient
Monitoring

• Cardiac toxicity
• Dose limiting
• Manifests itself CHF (edema, shortness of
  breath, dyspnea on exertion)
• Concern once cumulative lifetime dose gt300 mg/m2
• Significant risk once cumulative dose gt 450
  mg/m2.
• Obtain baseline MUGA to assess cardiac function,
  then after every 2-3 cycles unless new onset
  symptoms

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(No Transcript)
85
Zoledronic Acid Pamidronate
100
Zoledronic acid 4 mg
Pamidronate 90 mg
80
60
Patients with no event ()
40
20
0
0
100
200
300
400
500
Time after start of drug (days)
SREsskeletal-related events.Adapted with
permission from Rosen LS et al. Cancer J.
20017377-387.
86
2007 ASCO Practice Guidelines for ESA

• Chemo-Induced Anemia ESA
• Hg lt10 gm/dl-treatment option
• Hg of 10-12 gm/dl-Use clinical judgment
• Hg Target
• Hg up to 12 gm/dl
• Adjust doses to maintain target level.
• Reduce dose for any Hg increase gt 1g/dl in a 2
  week period or when Hg gt11.0.

87
2007 ASCO Practice Guidelines for ESA

• Discontinuing therapy for no response
• DC ESA if 6-8 week trial does not result in a 1-2
  gm/dl increase in Hg or a decrease in transfusion
  requirements Thromboembolic Risk
• Increases risk
• Concurrent use within disease states and other
  agents further increases this risk (i.e.- MM
  w/steroids and immune modulators)

88
2007 ASCO Practice Guidelines for ESA

• Iron monitoring and supplementation
• Recommended prior to initiation of treatment with
  an ESA, and periodically during treatment (iron,
  TIBC, transferrin, ferritin)