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Survivorship, Patient Engagement

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Title: 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

28
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)

46
(No Transcript)
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

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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

75
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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.

77
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.

83
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

85
Historical MM Tx
  • 1960s
  • Melphalan
  • Glucocorticoids (steroids)
  • 1970s-1980s
  • Combo chemo VAD
  • High dose chemo
  • Stem cell transplant (SCT)

86
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
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