Survivorship, Patient Engagement

1
Survivorship, Patient Engagement Side Effect
Management

• LLS Multiple Myeloma Conference
• Pewaukee, WI
• October 5, 2013
• (updated post conference)
• Mike Thompson, MD, PhD
• _at_mtmdphd
• Medical Director Early Cancer Research Program,
  Patient-Centered Research
• Aurora Research Institute

2
Outline

• COI / Participatory Medicine
• Resources
• MMSM Twitter Chat
• What is a Survivor
• Side Effects Management

3
Outline

• COI / Participatory Medicine
• Resources
• MMSM Twitter Chat
• What is a Survivor
• Side Effects Management

4
Potential Conflicts (or Convergence) of
Interests

• Novartis research funding (2006, Zometa)
• Celgene - MDS registry advisor (2012-)
• Seattle Genetics, Advisory Board (2013)
• ECOG Myeloma Core Committee
• NCI Myeloma Steering Committee
• ASCO Cancer Research Committee (2013-16)
• Aurora Health Care / ARI

5

• I WILL talk about off label use of products.

6
Patient Advocacy / Participatory Medicine and
e-Health

• LLS
• Stillwaters Cancer Support Group
• International Cancer Advocacy Network (ICAN)
• Best Doctors
• HealthTap
• Doximity
• ASCO Connection blogger
• MMSM Twitter Chat

7
Outline

• COI / Participatory Medicine
• Resources
• MMSM Twitter Chat
• What is a Survivor
• Side Effects Management

8
The Internet

• Is the Internet Really Making Me Stupid, Crazy,
  and Constantly Distracted?

http//lifehacker.com/5927763/is-the-internet-real
ly-making-me-stupid-crazy-and-constantly-distracte
d?utm_campaignsocialflow_lifehacker_twitterutm_s
ourcelifehacker_twitterutm_mediumsocialflow
9
Resources

• LLS www.lls.org
• http//www.canceradvocacy.org/toolbox/multiple-mye
  loma/
• http//www.mayoclinic.org/multiple-myeloma/symptom
  s.html
• Multiple Myeloma Personal Care Assistant
• International Myeloma Foundation
• www.myeloma.org
• ASCO
• http//www.cancer.net/patient/CancerTypes/Multipl
  eMyeloma
• Side Effects http//www.cancer.net/patient/Cancer
  Types/MultipleMyeloma?sectionTitleSide20Effects
  
• Cancer.Net
• mmsm engaged patients
• MPatient - http//www.mpatient.org/

10
National Coalition for Cancer Survivorship (NCCS)

• http//www.canceradvocacy.org/toolbox/multiple-mye
  loma/
• Cancer Survival Toolbox
• Side Effects And Symptom Management 

11
Outline

• COI / Participatory Medicine
• Resources
• MMSM Twitter Chat
• What is a Survivor
• Side Effects Management

12
Myeloma MMSM Twitter Chat

• Sunday nights, 9-10 pm
• Search / follow mmsm
• (multiple myeloma social media)
• http//twubs.com/mmsm
• Started 9/15/13 by _at_mtmdphd _at_myelomateacher
• Next 10/20/13
• Participants from Mayo, MDACC, UNC, etc

13
Outline

• COI / Participatory Medicine
• Resources
• MMSM Twitter Chat
• What is a Survivor
• Side Effects Management

14
What is a Survivor?
15
Survivorship DefinitionsVarious

• 5 yrs after Tx / cure
• "From the time of cancer diagnosis, through the
  balance of his or her life." 
• National Coalition of Cancer Survivorship The
  Office of Cancer Survivorship (NCI) Lance
  Armstrong Foundation

16
Many Cancer Survivors

• AACR
• In the US alone, there are 12 million cancer
  survivors
• http//ow.ly/6BXgg AACR cancerprogress
• AACR ?_at_AACR2 Oct
• In 1971, one of every 69 people was a cancer
  survivor. Today, it's one in 23.
  http//ow.ly/poyUS  CancerProgress13

17
The C Word

• ASH 2009
• Bart Barlogie used the word Cure in talking
  about MM
• Ken Anderson (DFCI) Vincent Rajkumar (Mayo)
  followed his talk and didnt disagree
• Prior we usually talked about MM as an incurable
  disease
• A paradigm shift?
• Not currently curable James Bond (Pt) 2012 WI
  LLS mtg

18
Curability of Multiple Myeloma ASH
2009Delasalle et al. 3864 (MDACC study)

• Conclusions Assuming that prolonged CR for more
  than 10 years translates into potential cure, we
  calculated a "cure fraction" of 2 for patients
  treated between 1987-1997.
• Such favorable outcome with potential cure should
  be more likely with current programs associated
  with more frequent early intensive therapy and
  CR.

19
MM Curability?(or chronic disease)

• Kathy Giusti 
• Founder and CEO of the MM Research Foundation
  (MMRF)
• 15 year multiple myeloma patient (2011)
• http//www.themmrf.org/about-the-mmrf/powerful-new
  s/press-releases/kathy-giusti-and-mmrf-featured-in
  -harvard-business-review.html

20
Mayo MM Survival
21
MM Survivors

• Survival/Prognostic tables based on old data.
• We are not curing everyone (yet), but
• New drugs treatment approaches are changing MM.
• MM Survivors will increase in number and
  need/demand new treatments and supportive care

22
I Will Survive
23
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

24
Side Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

25
Steroid S/E(Steroids backbone of MM Tx)

• Mental
• chemo brain
• irritability
• mood swings
• depression
• Insomnia
• General
• weight gain
• increased appetite
• general body swelling
• flushing, and sweating
• muscle cramping
• GI - heartburn, gas, and taste changes
• changes in sexual function
• and a letdown effect when steroids are stopped
  suddenly
• paradoxical fatigue

26
Diabetes Mellitus

• Avoid (relatively) the following
• Dex
• Thal/Dex
• Len/Dex
• Bortezomib/Dex
• Bortezomib - hypoglycemia

27
Sleep-shopping (or "Oops, I purchased what???")

• Once per week, I take 20 mg of dexamethasone,
  which is a steroid. As a result, I won't sleep at
  all if I don't take Ambien twice a week-- on the
  day I take dex and the day after. When I take
  Ambien, I mostly don't remember what I've done.
  Which means texting and phone calls can be
  comical. But last week, I encountered something
  potentially not comical. After an Ambien night, I
  woke up the next day, checked my email, and
  discovered that I went shopping in the middle of
  the night and bought things that I didn't want or
  need. I mean, they're kind of cool, but it was a
  big "I did what?" moment. So my shipments have
  arrived and here's what I ended up with
• 7/25/13 - http//lizzysmilez.blogspot.com/2013/07/
  night-shopping-or-oops-i-purchased-what.html

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OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

29
Bone Disease

• 80 MM Pts with bone disease depends on how
  you look
• A major source of
• pain
• complications
• death

30
Bone

• Low bone mass osteopenia or osteoporosis
• Lytic bone lesions
• Pain
• Pathologic fractures
• ONJ osteonecrosis of the jaw from
  bisphosphonate (or d-mab) Rx

31
Bone - Zoledronic Acid in MMUK MRC Myeloma IX
Data

• N 2000 MM Pts
• Zoledronic acid (Zometa) IV vs.
• oral (and less potent) cladronate (not avail in
  US)
• RESULTS Favored Zometa
• 50 fewer SRE
• Improved OS 16 (incr med OS by 5.5 mon)
• Increase PFS 12 (incr med PFS by 2.0 mon)
• Lancet Oncology (201112743-751)
• Lancet 20103761989-99

32
Bone - Zoledronic Acid in MMUK MRC Myeloma IX
Data

• Previously people with no bone lesions weren't
  considered for treatment with these agents, but I
  think we have shown convincingly that you can
  reduce the rates of SREs in patients even in
  patients who don't have bone disease at
  baseline, Dr. Morgan said.
• That's important, because if patients start out
  without bone lesions they don't get bone pain,
  but once they do have an SRE there is a chance it
  will impair their quality of life.
• Lancet Oncology (201112743-751)
• Lancet 20103761989-99
• Oncology Times 10 September 2011 - Volume 33
  - Issue 17 - pp 13,16

33
NCCN UpdatesVersion 1.2012

• Adjunctive treatment The panel now recommends
  bisphosphonate therapy for all patients receiving
  primary myeloma therapy. Previously it was
  recommended in all myeloma patients with
  documented bone disease. For treatment of
  hypercalcemia, if bisphosphonates is chosen, the
  panel prefers using zoledronic acid.

34
NCCN v 2.013

• Zoledronic acid (category 1 EBM)
• SMM
• consider Zometa in clinical trial
• Yearly bone XR survey
• Monitor renal fn ONJ
• Trial Zometa vs. denosumab (NCT01345019)

35
Bone

• OsteoCLASTs - bone-destroying cells
• OsteoBLASTs - bone-forming cells
• Treatments for bone disease include
• Drugs
• Radiation
• Vertebro- or kyphoplasty
• Surgery (less common now)

36
Bone

• Bisphosphonates
• inhibit the activity and formation of
  bone-destroying cells.
• pamidronate (Aredia) - less effective
• zoledronic acid (Zometa)
• RANK Ligand Inhibitor
• Xgeva (denosumab, Amgen)
• Bortezomib (Velcade)
• Transient rather than permanent new bone
  formation
• Parathyroid hormone (PTH, teriparatide, Forteo,
  Lilly) a drug used to treat some patients with
  osteoporosis has a benefit in mice and may be
  safe for patients with myeloma
• New drugs Not approved
• DKK-1 inhibitors
• BHQ880 (Novartis) - antibody
• Activin A inhibitor
• ACE-011 (Sotatercept, Acceleron/Celgene)
  anemia Tx?
• bone morphogenetic protein receptor type 1A
  (BMPR1A) inhibitor
• ACE-661 (Acceleron)

37
Side Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

38
Infection

• MM results (usually) in the expansion in one
  (mono-) type clone (-clone) monoclonal
  (M-spike) of Ig
• Other Igs can be reduced
• Tx can reduce immunity
• Most common cause of MM death is infection

39
Infection

• IVIg considered
• Vax PVX, Influenza
• lower Ab response, but still advised
• Px for high dose Dex
• PCP, herpes, antifungal
• Px for bortezomib (or MM in general)
• Herpes zoster px

40
Side Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

41
Fatigue

• The most common symptom of multiple myeloma is
  fatigue, found in 70 percent of patients at
  diagnosis. Mayo
• http//www.mayoclinic.org/multiple-myeloma/symptom
  s.html (?)
• Anemia consider Epo (VTE risk), RBC Tx
• Poor sleep
• Decr caffeine
• Good sleep hygiene
• Pain control
• Exercise

42
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

43
Sexual Side Effects

• Danish researchers recently found that patients
  who underwent SCT frequently experienced sexual
  dysfunction, sometimes for extended periods of
  time after transplantation. 
• Reduced sexual function -gt lower quality of life
  (QOL)
• Decreases in
• sexual activity (38)
• ability to have sex (36)
• pleasure from sex (31)
• interest in sex (28)
• Thygesen et al. The impact of hematopoietic stem
  cell transplantation on sexuality a systematic
  review of the literature. Bone Marrow
  Transplantation , (29 August 2011)
• Myeloma Beacon - http//www.myelomabeacon.com/news
  /2011/09/19/researchers-find-high-rates-of-sexual-
  dysfunction-after-stem-cell-transplantation/

44
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

45
Neuropathy

• Tingling and pain in the hands, arms, feet, and
  legs (known as peripheral neuropathy, PN).
• Treatments for myeloma can make this neuropathy
  worse
• Combinations of drugs associated with PN can
  greatly increase the risk (VTD).
• However, other combinations may decrease the risk
  of PN (Hsp90 or HDACi)

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47
Neuropathy

• MM (before Tx)
• Tx related
• Thalidomide
• Much less with other IMiDs
• Bortezomib
• Less with SQ or qWK dosing
• not used much now
• Vincristine
• Platinums

48
NeuropathyMechanism (Thalidomide)

• Thalidomide
• Researchers looked at MM pts (n27 MM 30 ctrls)
  treated with thalidomide
• clinical and electrophysiological assessment of
  peripheral sensory nerves
• axonal and demyelinating abnormalities
• Clinically
• arm and heat-pain detection thresholds were
  elevated
• threshold for skin cooling was decreased
• Bilinska M et al. Pol Merkur Lekarski. 2011
  Aug31(182)86-91.

49
Neuropathy Bortezomib Dosing

• FDA approved
• 1.3 mg/m2 IV d1,8,11 q21d
• PN 36 total Gr 3 7, Gr 4 lt1
• Weekly
• 1.6 mg/m2 IV weekly
• REF Greco et al. ASCO 2006 7547
• N37 (26 evaluated)
• PN 0
• Subcutaneous (SQ)
• 1.3 mg/m2 SQ d1,4,8,11 q21
• REF Moreau et al. Lancet Oncol 12(5)431-440
• N222 (145 SQ, 77 IV) 3 RCT
• PN SQ 38 vs. IV 53 (total)
• PN gtgr3 SQ 57 vs. IV 70
• NOTE No data for SQ qWEEK. SQ may be good for
  home. Weekly decr PN

50
Neuropathy

• 2011 -- No randomized controlled trials (RCTs)
  published of any drug or supplement in myeloma
  patients looking to prevent or treat peripheral
  neuropathy
• Vitamin B6 and nutritional supplements with amino
  acids, pain medicines,
• anti-depressants, NSAIDs (watch kidneys!)
• Neuropathy meds anti-seizure drugs
• Duloxetine (Cymbalta) ?

51
Effect of Duloxetine on Pain, Function, Quality
of Life Among Patients with Chemotherapy-Induced
Painful Peripheral Neuropathy A Randomized
Clinical Trial

• Ellen M. Lavoie Smith, PhD et al.
  JAMA. 2013309(13)1359-1367.
• Importance There are no known effective
  treatments for painful chemotherapy-induced
  peripheral neuropathy.
• Objective To determine the effect of duloxetine,
  60 mg daily, on average pain severity.
• Design, Setting, and Patients Randomized,
  double-blind, placebo-controlled crossover trial
  at 8 National Cancer Institute (NCI)funded
  cooperative research networks that enrolled 231
  patients who were 25 years or older being treated
  at community and academic settings between April
  2008 and March 2011. Study follow-up was
  completed July 2012. Stratified by
  chemotherapeutic drug and comorbid pain risk,
  patients were randomized to receive either
  duloxetine followed by placebo or placebo
  followed by duloxetine. Eligibility required that
  patients have grade 1 or higher sensory
  neuropathy according to the NCI Common
  Terminology Criteria for Adverse Events and at
  least 4 on a scale of 0 to 10, representing
  average chemotherapy-induced pain, after
  paclitaxel, other taxane, or oxaliplatin
  treatment.
• Interventions The initial treatment consisted of
  taking 1 capsule daily of either 30 mg of
  duloxetine or placebo for the first week and 2
  capsules of either 30 mg of duloxetine or placebo
  daily for 4 additional weeks.
• http//jama.jamanetwork.com/arti
  cle.aspx?articleid1674238

52

• Main Outcome Measures 
• The primary hypothesis was that duloxetine would
  be more effective than placebo in decreasing
  chemotherapy-induced peripheral neuropathic pain.
  Pain severity was assessed using the Brief Pain
  Inventory-Short Form average pain item with 0
  representing no pain and 10 representing as bad
  as can be imagined.
• Results 
• Individuals receiving duloxetine as their initial
  5-week treatment reported a mean decrease in
  average pain of 1.06 (95 CI, 0.72-1.40) vs 0.34
  (95 CI, 0.01-0.66) among those who received
  placebo (P  .003 effect size, 0.513).
• The observed mean difference in the average pain
  score between duloxetine and placebo was 0.73
  (95 CI, 0.26-1.20).
• Fifty-nine percent of those initially receiving
  duloxetine vs 38 of those initially receiving
  placebo reported decreased pain of any amount.
• Conclusion and Relevance 
• Among patients with painful chemotherapy-induced
  peripheral neuropathy, the use of duloxetine
  compared with placebo for 5 weeks resulted in a
  greater reduction in pain.
• Trial Registration clinicaltrials.gov
  Identifier NCT00489411

53
Neuropathy TreatmentsNot proven

• http//www.myelomabeacon.com/forum/preventing-peri
  pheral-neuropathy-t24.html
• Dr. Paul Richardson from the Dana-Farber Cancer
  Institute said "Please see below for some
  suggestions - please note that dose reduction and
  schedule change are key to minimizing PN
  supplements should not be taken on the same day
  of Velcade (bortezomib) administration as there
  are reports of antagonism pre-clinically (ie in
  the lab), although this has not been shown in
  patients.
• All supplements must be discussed with and
  approved by the treating physicians concerned.
  Supplements should be taken with food unless
  otherwise indicated. MULTI-B COMPLEX
  VITAMINS with B1, B6, B12, folic acid and
  other B6 should be approximately 50mg daily,not
  to exceed 100mg per day Folic acid should be 1mg
  per day VITAMIN E 400 IU daily VITAMIN
  D 400-800 IU daily 

54
Neuropathy Treatments(cont)

• FISH OILS OMEGA-3 FATTY ACIDS (EPA and
  DHA) MAGNESIUM Suggested doses include 250mg
  twice a day (OTC) Alternatively 400mg daily by
  prescription with dose frequency dependent on
  serum magnesium levels May cause diarrhea in
  larger doses POTASSIUM Either as provided by
  the treating physician or foods that are rich in
  potassium (e.g. bananas, oranges and
  potato). TONIC WATER (Seltzer water) Drink one
  glass in evening and any other time cramping
  occurs ACETYL L- CARNITINE 500mg twice a day
  with food Can take up to 2000mg a
  day. ALPHA-LIPOIC ACID 300mg to 1000mg a day
  with food Glutamine 1g up to three times a day
  with food"

55
Neuropathy

• Other potential Therapies
• Massage
• Accupuncture
• reTouch is the first medical device designed to
  restore sensation to those suffering with
  peripheral neuropathy.
• https//www.facebook.com/retouchneuropathy
• Spinal Cord Stimulators ?
• http//professional.medtronic.com/mri/surescan-mri
  -radiologists/scs/surescan-system/index.htm.Ui44b
  9IpIYU
• ASCO Cancer.Net Managing Peripheral
  Neuropathy
• http//www.cancer.net/patient/AllAboutCancer/Can
  cer.NetFeatureArticles/SideEffects/ManagingPer
  ipheralNeuropathy

56
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

57
Financial toxicity

• Household finances
• Health Insurance
• Applying for insurance or filing claims can be a
  full time job
• Financial counselors at your physicians office
• LLS
• WI Cancer Treatment Fairness Act 
• http//capwiz.com/myeloma/issues/alert/?alertid62
  393536
• Rights in the workplace
• ACA coverage for most

58
Financial toxicity

• Financial Aid
• The Leukemia Lymphoma Society's (LLS's) Patient
  Financial Aid Program provides a limited amount
  of financial assistance to help patients who have
  significant financial need and are under a
  doctor's care for a confirmed blood cancer
  diagnosis.
• LLS's Co-Pay Assistance Program offers financial
  support toward the cost of insurance co-payments
  and/or insurance premium costs for prescription
  drugs. Patients must qualify both medically and
  financially for this program.
• Information and resources regarding insurance,
  managed care and employment issues are provided
  in Insurance and Employment.
• 1-800-955-4572
• http//www.lls.org//diseaseinformation/getinforma
  tionsupport/financialmatters/

59
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

60
Digestive / GI

• Constipation
• Pain meds
• Drugs (bortezomib)
• Hypercalcemia
• Diarrhea
• Nausea / Vomiting

61
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Cardiovascular
• Renal
• 2nd malignancies

62
Cardiovascular VTE NCCN Guidelines v.1.2012

• Heart SE decreased ejection fraction
• Anthracyclines
• Adriamycine
• Doxil liposomal anthracycline
• VTE PE or DVT
• Associated with Thal, Len/Dex
• Px A/C rec (NCCN v1.2012) if above meds
• Px
• ASA usually not effective for VTE, but some
  benefit in MM
• Warfarin
• LMWH

63
Pt with thrombosis risk

• Avoid the following
• thalidomide
• bevacizumab (eg, Bev/Rev/Dex)
• Above Epo

64
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

65
Renal Failure in Myeloma

• Mechanism
• Light chain cast deposition tubule obstruction
  (myeloma kidney)
• Obstruction by a plasmacytoma
• Hypercalcemia, hyperuricemia
• Renal amyloid
• Recurrent pyelonephritis
• May develop RTA2 (Fanconi syndrome)
• Prevention
• Avoid NSAIDs, contrast
• High urinary output (3L/d)

66
Renal DysfunctionNCCN Guidelines v.2.2013

• Maintain hydration to avoid renal failure
• Avoid use of NSAIDs
• Avoid IV contrast
• Plasmapharesis (category 2B)
• Not a contraindication to transplant
• Monitor for renal dysfunction with chronic use of
  bisphosphonates

67
Renal Failure TreatmentBortezomib

• Subset analysis of SUMMIT CREST
• S/E similar in normal vs decr CrCL
• Crt level not affected
• Response
• CrCL (mL/min) n ORR ()
• gt80 105 45
• 51-80 99 33
• lt 50 52 25
• lt 30 10 30
• Jagannath et al. Cancer 20051031195-1200

68
Renal Failure Treatment

• Bortezomib
• FDA approved in renal insuff/failure
• VD
• VTD
• VAD Vincristine/Adriamycin/Dex
• thalidomide
• lenalidomide possible PrECOG PrE1003 study P
  I/II ongoing

69
Renal Recovery

• Reversibility of Renal Failure in Newly Diagnosed
  Patients with Multiple Myeloma and the Role of
  Novel Agents
• group A n28 conventional chemo (CC)
  Dexa-based regimens (VAD, VAD-like regimens,
  melphalan plus Dexa)
• group B n38 - IMiDs-based regimens (thalidomide
  or lenalidomide with high dose Dexa and/or CTX or
  melphalan)
• group C n16 - bortezomib-based regimens with
  Dexa
• A/B/C Renal CR 43 / 50 / 69 (p0.2)
• A/B/C - RCRRPR 50 / 57 / 81 (p0.1)
• Roussou et al. ASH 2009 Abstr955

70
Renal Recovery

• In multivariate analysis bortezomibbased
  regimens (p0.02, OR 7, 95 CI 1.5-25) and
  CrClgt30 ml/min (p0.002, OR 6.1, 95 CI
  2.5-22.5) were independently associated with a
  higher probability of RCRRPR
• Novel agent-based regimens can improve renal
  function in most patients furthermore
  bortezomib-based regimens improve renal function
  to a higher degree and significantly more rapidly
  than CC plus Dexa-based or IMiD-based regimens
  even in patients with severe renal impairment.
• We conclude that bortezomib-based regimens may be
  the preferred treatment for newly diagnosed
  myeloma patients who present with renal
  impairment.
• Roussou et al. ASH 2009 Abstr955

71
Orlowski tweet

• MD Anderson trial for relapsed/refractory
  myeloma patients with renal failure
  Pomalidomide/Dex 1.usa.gov/UZuvW6.
  1-855-MYELOMA.

72
OutlineSide Effects

• Steroid SE
• Bone
• Infection
• Fatigue
• Sexual
• Neuropathy
• Financial toxicity
• Digestive / GI
• Cardiovascular
• Renal
• 2nd malignancies

73
2nd Malignancies in MM

• http//www.ascopost.com/articles/august-15-2011/se
  cond-primary-malignancies-explored-in-multiple-mye
  loma.aspx

74

• http//www.ascopost.com/articles/august-15-2011/se
  cond-primary-malignancies-explored-in-multiple-mye
  loma.aspx
• Three randomized controlled trials presented at
  the 2010 Annual Meeting of the American Society
  of Hematology (ASH) suggested that treating
  multiple myeloma with lenalidomide (Revlimid)
  increased the risk of second primary
  malignancies of particular concern is
  transformation to acute myeloid leukemia or
  myelodysplastic syndromes
• Celgene letter p. 3 SPM Summary

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76
MDS Mechanism?Epo Gene

• Polymorphism of the erythropoietin gene promotor
  and the development of myelodysplastic syndromes
  subsequent to multiple myelomaO Landgren, W Ma,
  R A Kyle, S V Rajkumar, N Korde and M
  AlbitarLeukemia , (16 September
  2011) oi10.1038/leu.2011.262AbstractThe
  occurrence of acute myeloid leukemia (AML) and
  myelodysplastic syndromes (MDSs) following
  multiple myeloma has been recognized for
  decades.1 Alkylating agents have long been
  considered to be part of the cause.2, 3, 4,
  5 Some, but not all, smaller investigations have
  reported that higher cumulative melphalan dose
  and longer duration of melphalan therapy are
  associated with an increased risk of AML.6,
  7 The role of nontreatment-related factors is
  largely unknown.
• Previous studies (Ma et al BMC Med Genet 2010)
  showed the association with the the
  erythropoietin (EPO) promoter single nucleotide
  polymorphism (SNP) G/G for rs1617640 in MDS.
• This small (n32 evaluable total) nested
  case-control study showed
• MM -gt MDS - 4/15 (27)
• MM -gt no MDS - 2/15 (12)
• These are small numbers, but agree with
  non-myeloma specific patient risk of MDS.
• While this study needs to be validated in larger
  sample sets, it will be interesting to see if it
  holds up and perhaps more importantly the
  genotype can suggest which type of chemotherapy
  agents an individual patient could receive to
  decrease the risk of MDS.
• This could be a very important "survivorship-omics
  " issue for MM treatment.

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SPM may not be MM specificCLL

• Second cancer incidence and cancer mortality
  among chronic lymphocytic leukaemia patients a
  population-based study.
• Background
• Patients with chronic lymphocytic leukaemia (CLL)
  are known to have increased risks of second
  cancer.
• The incidence of second cancers after CLL has not
  been reported in detail for Australia, a country
  with particularly high levels of ultraviolet
  radiation (UVR).
• Methods
• The study cohort comprised of all people
  diagnosed with a primary CLL between 1983 and
  2005 in Australia. Standardised incidence ratios
  (SIRs) and standardised mortality ratios (SMRs)
  were calculated using Australian population
  rates.
• Results
• Overall, the risk of any second incident cancer
  was more than double that of the general
  population (SIR2.17, 95 confidence interval
  (CI)2.07, 2.27) and remained elevated for at
  least 9 years after CLL.
• Risks were increased for many cancers,
  particularly melanoma (SIR7.74, 95 CI6.85,
  8.72).
• The risk of melanoma increased at younger ages,
  but was constant across gt9 years of follow-up.
• CLL patients also had an increased risk of death
  because of melanoma (SMR4.79, 95 CI3.83, 5.90)
  and non-melanoma skin cancer (NMSC SMR17.0,
  95 CI14.4, 19.8), suggesting that these skin
  cancers may be more aggressive in CLL patients.
• Conclusion
• We speculate that a shared risk factor, such as
  general immune suppression, modulated by UVR
  exposure may explain the increased risk of
  melanoma and NMSC in CLL patients.
• Royle et al. Br J CA 105, 1076-1081 (27
  September 2011)

78
Conclusions

• More Treatments
• Improved Survival
• More survivors
• Online, LLS resources
• MMSM Twitter Chat Sun 10/20 9-10pm
• WI has great myeloma people

79
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80
Contact Info

• Aurora 414-219-4763
• Twitter _at_mtmdphd

81
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82
SPMBiRD regimen, Single Institution

• Incidence of second primary malignancies (SPM)
  after 6-years follow-up of continuous
  lenalidomide in first-line treatment of multiple
  myeloma (MM). Rossi et al ASCO 2011 8008.
  Abbreviated...
• Background 
• Clarithromycin (Biaxin), lenalidomide and
  dexamethasone (BiRD)
• N72
• OR 90.3, 38.9 (sCR/CR), 73.6 VGPR
• Results 
• 68 evaluable pts
• SPM 11 new diagnoses (incidence of 16) after an
  average of 31 cycles (range 3-68) of lenalidomide
  (BiRd).
• SPM 6/11 skin cancers (4 BCC, 2 SCC) 2 colon, 1
  prostate, 1 pancreas and 1 metastatic melanoma.
• 0 MDS/AML.
• Mean time to SPM diagnosis was 35 months (range
  5-64).
• Conclusions 
• No cases of secondary MDS/AML were seen, in
  contrast to reports in relapse/refractory pts who
  received Rev as third or fourth line therapy
  (Reece, Goswami ) or as post-transplant
  maintenance (Attal , McCarthy).
• Frequency of SPM is similar to 2010 SEER data for
  non-MM individuals of similar age.
• As survival in pts with MM continues to improve,
  so will our understanding of the long-term
  effects of novel agents.
• Design of regular cancer screening programs (derm
  and GI) of MM pts should be regularly implemented.

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MM BackgroundClinical Features

• Early MM often asymptomatic
• Common clinical features
• C hyper-Calcemia
• R renal (kidney) problems
• A anemia
• B bone pain
• Fatigue
• Recurrent infections
• Neuropathy

84
MM Epidemiology

• Incidence 4-5/100,000
• 2010 est. cases gt20,000
• 2008 est. cases 19,9201 ,deaths 10,6901
• Median age at dx 702,3
• 7 before age 55
• 2 before age 40
• 0.3 before age 30
• 1. Jemal A, et al. Cancer Statistics, 2008. CA
  Cancer J Clin 20085871-96
• 2. Ries LAG, et al. SEER Cancer Statistics
  Review, 1975-2004. National Cancer Institute.
  Bethesda, MD
• Available at http//seer.cancer.gov/csr/1975_2004
  . Accessed April 10, 2008.
• 3. Attal et al, NEJM 1996, IMF90

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Historical MM Tx

• 1960s
• Melphalan
• Glucocorticoids (steroids)
• 1970s-1980s
• Combo chemo VAD
• High dose chemo
• Stem cell transplant (SCT)

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Historical MM Tx

• 1990s
• bisphosphonates
• 2000-Present new drugs!
• thalidomide
• bortezomib
• lenalidomide
• bortezomib/Doxil (liposomal adriamycin) (rel/ref)
• Others

87
LinkedIn Forum (LLS) 2011Multiple Myeloma
Survivorship Issues?

• http//www.linkedin.com/groupItem?viewgid39708
  typememberitem60250765qid7421bb82-2a51-41a5-a
  594-d8ae47c7c67agoback2Egmp_39708
• CIPN chemo-induced peripheral neuropathy
• Steroid side effects
• bone loss
• insomnia/mania
• paradoxical fatigue
• other psychiatric problems
• hyperglycemia/worsened diabetes,
• swelling
• increased weight