Understanding Myeloma to
Provide Optimal Patient Care
(for Healthcare Providers)
LLS WI MM Conference
Sept 13, 2014
Mike Thompson, MD, PhD
@mtmdphd - #mmsm
Medical Director, Early Phase Cancer Research
Co-PI Aurora NCORP
Aurora Research Institute
Aurora Health Care (@Aurora_Health, @Aurora_Cancer)
Potential Conflicts
(or Convergence) of Interests:
ECOG / NCI / ASCO
• ECOG-ACRIN MM Core Committee – 2009• #EAOnc @EAOnc
• NCI MM Steering Committee – 2013-2016
• ASCO Cancer Education Comm on Lymphoma
& Plasma Cell Disorders 2014-2017
Potential Conflicts
(or Convergence) of Interests:
Industry etc
• Celgene - Connect MDS/AML Registry – Scientific
•
Steering Committee (SSC) Member
Onyx Pharmaceuticals – MM Global Registry
Steering Committee
• International Cancer Advocacy Network (ICAN),
Sr. Editor, Myeloma
• Stillwaters Cancer Support Group – 2008-2014
• Xconomy Advisor
• #mmsm Myeloma Twitter Discussion Group
• Started 09/15/13
Outline
•
•
•
•
Other LLS MM 2014 Session Content
MM Background (Brief)
#MMSM Twitter Chat
The New world of MM
• Cost, Cure, Survivorship, QOL
• Goals – sCR, MRD
• Immuno-Onc / Vaccines
• Side Effects & Supportive Care
Outline
•
•
•
•
Other LLS MM 2014 Session Content
MM Background (Brief)
#MMSM Twitter Chat
The New world of MM
• Cost, Cure, Survivorship, QOL
• Goals – sCR, MRD
• Immuno-Onc / Vaccines
• Side Effects & Supportive Care
Other LLS 2014 Session Content
Core Talks
•
•
•
•
Dr. Pasquini – MM Hx & Stnd Tx
Dr. Callander – MM management: neuropathy, neutropenia, fatigue
Dr. Maguire – Survivorship
Dr. Hari - Pipeline: New, emerging, & clinical trials for myeloma
Breakout Talks
•
•
•
•
Riccobono - Caring for the Caregiver
Hari / Pasquini – SCT
Gruber / Straseski - Pt advocacy, access, affordability, costs
Sanchez - Lab values and imaging
Outline
•
•
•
•
Other LLS MM 2014 Session Content
MM Background (Brief)
#MMSM Twitter Chat
The New world of MM
• Cost, Cure, Survivorship, QOL
• Goals – sCR, MRD
• Immuno-Onc / Vaccines
• Side Effects & Supportive Care
Multiple Myeloma
• MM is a cancer of plasma cells
• Plasma cells are highly differentiated
B-cells
• Many of the laboratory tests and
clinical features are based on this
unusual cell of origin
MM Background
Clinical Features
• Early MM – often asymptomatic
• Common clinical features:
• C – hyper-Calcemia
• R – renal (kidney) problems
• A – anemia
• B – bone pain
• Fatigue
• Recurrent infections
• Neuropathy
MM SEER Data
• 2014 incidence: 24,050
• Myeloma represents 1.4% of all new cancer cases in
the U.S.
• The %-age doesn’t matter if you have it
• Number of New Cases and Deaths per 100,000:
• The number of new cases of myeloma was 6.1
•
•
per 100,000 men and women per year.
The number of deaths was 3.4 per 100,000 men
and women per year.
These rates are age-adjusted and based on
2007-2011 cases and deaths.
http://seer.cancer.gov/statfacts/html/mulmy.html
MM: New Cases vs. Age
http://seer.cancer.gov/statfacts/html/mulmy.html
MM: Deaths vs. Age
Most deaths in older patients, but few trials designed for that age.
Optimal care requires elderly, poor PS, high comorbidity “real life” studies and
CCDR.
http://seer.cancer.gov/statfacts/html/mulmy.html
MM SEER Data
• Prevalence (2011): 83,367 in US
• 5yr OS (2004-2010): 44.9% (2X 1985)
Year
1975
1980
1985
1990
1994
1998
2002
2006
5-Year
Relative
Survival
26.3%
25.8%
27.0%
29.6%
30.7%
33.9%
39.5%
45.1%
More Myeloma Patients
Longer Lives with MM
• Increasing MM incidence
• Based on older age
• Increasing MM prevalence
• Improved Rx and supportive care
• Therefore MM optimization of care goals
include disease control as well as QOL,
cost/value, and supportive care.
• More research into elderly
•
Freiburg Comorbidity Index in 466 Multiple #Myeloma Patients & Combo w/ ISS
Highly Predictive for Outcome http://ow.ly/oO4T9 #mmsm
http://seer.cancer.gov/statfacts/html/mulmy.html
Survivorship
"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
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 didn’t disagree
• Usually talk about MM as an
incurable disease
• 2009 - paradigm shift?
MM Curability?
(or chronic disease)
• Kathy Giusti
• Founder and CEO of the MM Research
Foundation (MMRF)
• 16 year multiple myeloma patient
• Dx 1998
http://www.themmrf.org/about-the-mmrf/leadership/mmrf-founders.html
“Curability of Multiple Myeloma”
ASH 2009
Delasalle 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.
Outline
•
•
•
•
Other LLS MM 2014 Session Content
MM Background (Brief)
#MMSM Twitter Chat
The New world of MM
• Cost, Cure, Survivorship, QOL
• Goals – sCR, MRD
• Immuno-Onc / Vaccines
• Side Effects & Supportive Care
Myeloma #MMSM Twitter Chat
(Optimizing outreach & education)
• At ASH 2012 Dr. Matthias Weiss and colleagues in the NCI
Myeloma Steering Committee (MYSC) Accrual Working
Group (AWG) had a poster "Significant Barriers to Accrual
(BtA) to NCI Sponsored Multiple Myeloma – Clinical Trials (MMCT): A Step towards Improving Accrual to Clinical Trials"
(http://ow.ly/hrRSs).
They then went on at ASCO 2013 identify strategies to
overcome those barriers.
(http://meetinglibrary.asco.org/content/114090-132)
• One of those strategies included to:
"...educate patients and
providers about the significance
of a new CT [clinical trial] using
social media..."
#mmsm = MM Social Media
Hashtag Folksonomy for Cancer Communities on Twitter
Matthew S. Katz, MD (@SubatomicDoc) – ASCO Connection – 7/3/13
• “For two years, I’ve participated in #bcsm, a rich breast cancer
and social media community founded on Twitter. It has
encouraged me to ask: why not design similar resources for
people with other diseases?
• Twitter allows real-time interactions.
• Hashtags allow you to classify tweets, so that they can reach
certain audiences.
• It also permits tweetups, online meetups that can discuss
pertinent issues.
• #bcsm has done this superbly and is enriching for the
participating patients, advocates, caregivers, and providers.”
#mmsm Origin 1 year ago
08/29/13 – ASCO Connection Post
Online Patient Communities for the EPatient: “Betwixt and Between” a New
Patient and an Expert
http://connection.asco.org/Commentary/Article/ID/3645/Online-Patient-Communities-for-the-EPatient-Betwixt-and-Between-a-New-Patient-and-an-Expert.aspx
09/15/13 – First #mmsm Twitter Chat
#mmsm Topics
Moderated by @mtmdphd & @MyelomaTeacher
Date
Topic
People
•
•
•
•
•
•
•
•
•
•
•
09/15/13
Online Info, SMM
Rajkumar, Orlowski
10/20/13
Induction; VRd vs CfRd
Kumar
11/16/13
ECOG-ACRIN Mtg
Thompson
01/26/14
Allo SCT in MM
Hari
02/23/14
Racial Disparities in MM
Rajkumar
03/16/14
Clinical Trials in MM
Chmielewski
05/18/14
Can we cure MM?
Fonseca
06/29/14
Amyloidosis
Weiss
07/27/14
MRD
Landgren
08/24/14
MM Risk Assessment
Usmani
09/07/14
Crowdfunding for MM Research
Ahlstrom
Crowdsourcing
"...we must crowd-source the
change we want to see in the
world. Social media allows
that to happen..."
- @FarrisTimimi
- in Bringing Social Media
-
#Revolution to Health Care
Mayo Clinic Center for Social
Media (#MCCSM)
Can We Build A Kickstarter For
Cancer?
A few concepts
An educated & engaged (via social media & IRL) public
necessary to sustain a national clinical trials infrastructure
Should clinical trials be crowdsourced? @OncologyTimes
http://ow.ly/v5v0F #clinicaltrials
Let’s “Connect The Dots” Faster -- Can We Build A
Kickstarter For Cancer?
Forbes ow.ly/nB8Ho
"funding a “virtual biotech” for a single patient"
"..create a novel clinical trial format-let’s call it Phase 1.5 or
2.5"
Presented by: Mike Thompson, MD, PhD
@mtmdphd
Crowdsourcing Example
• Using social media, now positioned to:
• Crowdsource innovative research
•
•
•
ideas from the MM medical
community
Vet ideas with scientific advisory
board
Crowdvote for most interesting
opportunities
Crowdfund for innovative ideas not
funded by traditional research/trial
funding sources
Crowdsourcing
Medical Community
Oncologists/
Specialists/
Researchers
Patient Community
Cooperative
Research
Groups
FB Patient
Groups
Twitter
Feeds
Idea crowdsourcing secondary input
(Thalidomide Example)
Idea crowdsourcing
Initial scientific vetting
FB Family/
Caregiver
Groups
Crowd Voting/Ranking Process
socialized via social media
Short List Ideas
Possible crowdfunding opportunities
for early-stage not funded by traditional sources
Presented by: Mike Thompson, MD, PhD @mtmdphd
Patient Community Socialization
Myeloma Tweets
• Comparison of 2012 to 2013 MD Twitter use about cancer –
linked to MD National Provider Identifier (NPI)
• 20% Increase
• Quadrupled MD conversations
about multiple myeloma
• NCI ECOG MM studies
• Increased recognition
• Increased accrual (correlative, not nec causative)
• Coordination b/w SWOG & ECOG for
”U.S. Frontline Study”
An analysis of cancer-specific Twitter conversations among physicians in 2013 @brianreid et
al. #ASCO14 Abstract e17644 ow.ly/xcxgz
Multipe Myeloma Social Media
(#mmsm) Twitter Discussion (Chat)
Sunday nights, 8-9 pm CT
May change date/time to weekday
Search / follow #mmsm
Getting Started
1. Create a Twitter account (see info below)
2. Search & follow #mmsm (eg, as a separate
column on HootSuite or other application)
3. And/or use http://tweetchat.com/room/mmsm
#mmsm Suggested Topics?
Outline
•
•
•
•
Other LLS MM 2014 Session Content
MM Background (Brief)
#MMSM Twitter Chat
The New world of MM
• Cost, Cure, Survivorship, QOL
• Goals – sCR, MRD
• Immuno-Onc / Vaccines
• Side Effects & Supportive Care
“Optimal Theray” may include
cost considerations
• Curable – high upfront cost worth it
• Non-curable – what value are we
getting? Is PFS sufficient or OS
• What is the value of QOL? How do we
demonstrate QOL?
• Does “survivorship” care help?
• Assumptions vs. data?
Goals of Care?
• PFS
• OS
• ORR
• Lower ORR in Rd vs. RD but better OS
• sCR after Auto SCT
• Kapoor et al. JCO 2013 http://www.ncbi.nlm.nih.gov/pubmed/24248686
• Minimal Residual Disease (MRD)
• Cure
• And how defined?
Role of SCT
(beyond scope of my talk)
• Older Patients with Myeloma Derive Similar Benefit
from Autologous Transplantation - Sharma et al. BBMT
http://ow.ly/AhkCP
• Importance of achieving stringent complete response
(sCR) after autologous SCT in multiple
myeloma.ow.ly/sZ980
• Cost-effectiveness analysis of early v late auto SCT
in multiple myeloma – Pandya et al. http://ow.ly/B7OGv
• CPI-adjusted 2012 costs
• eASCT $249 236
QALY 1.96
• dASCT $262 610
QALY 1.73
• Prior studies showed no OS benefit of eASCT vs
dASCT – Dunavin et al. 2013 Leuke Lymphoma
Outline
•
•
•
•
Other LLS MM 2014 Session Content
MM Background (Brief)
#MMSM Twitter Chat
The New world of MM
• Cost, Cure, Survivorship, QOL
• Goals – sCR, MRD
• Immuno-Onc / Vaccines
• Side Effects & Supportive Care
MM Immune System
• Understanding of the MM immune system is not complete
• MM patients are living longer WITH disease
• Common reason for hospitalization or death in MM is
infection.
• Despite knowing about this increased risk of infections we
have a poor understanding of the immunologic response
and predictive factors to vaccines such as influenza and
pneumococcal in MM.
• Understanding may help us better prophylax and treat MM
and other hematologic patients.
Vaccination in MM (1)
1980 - Lazarus et al. -- w.ly/x10Kg
• ~30% signif Ab response to immunization (14-valent
pneumococcal)
• low cost, low risk
• "...may be prudent medical practice to vaccinate
patients with myeloma.“
1994 – Chapel et al. --http://ow.ly/sEFaz
• n=54 plateau phase MM
• PV 57% response rate
2007 – Yoshida – 30-40% PV effectiveness
Vaccination in MM (2)
2013 - Karlsson et al. - http://ow.ly/BrNJw
• N=56 MM, WM, MGUS
• Poor vaccine response in multivariate analysis
included hypogammaglobulinemia and concurrent
chemotherapy.
2013 ASH - Hahn - http://ow.ly/sDhZr
• N=48 - Flu vax x1 = in 20-40% Ab response
• N=24 – Flu vax x2 – roughly double Ab response
2014 - Whitaker et al. - http://bit.ly/1s7J7Rv
• Room for Improvement: Immuniz for Pts w/
Monoclonal B-Cell Lymphocytosis or CLL – so may
be a B-cell cancer issue
Vaccinating MM Pts
• As an initial step we will retrospectively evaluated the
current vaccination practice patterns at Aurora Health
Care using the EMR and data analytics.
• N = 1131
• Alemu AW, Richards JO, Singh M, Mandler JK, Oaks
MK, PhD, Blundon JL, Thompson MA. Multiple
Myeloma Vaccination Patterns from a Large Health
System: An Example of Cancer Care Delivery
Research (CCDR). ASH 2014. San Francisco, CA.
Abstract ID #68978. Submitted.
• There is room to optimize vaccinations
Sample Collection Study
The Immune Response Following Vaccination in Multiple Myeloma Patients – VLCC
ACCRA Award – PI: Thompson
• We will characterize immune parameters in multiple
myeloma patients and controls.
• Starting in Oct 2014
• Pending IRB approval
• SOC vaccinations (Flu, PV) and baseline and 4 other
blood draws
• Baseline data = platform for future
• Then
• interventional studies
• Flu
• PV
• Others
• Evaluate vs. various Chemos, new mAbs, other
immunotherapies
• ? Immune panel subsets with varied outcomes
Survival curves for the overall population with
and without the occurrence of Mayan doomsday.
Wheatley-Price P et al. CMAJ 2012;184:2021-2022
©2012 by Canadian Medical Association
Outline
•
•
•
•
Other LLS MM 2014 Session Content
MM Background (Brief)
#MMSM Twitter Chat
The New world of MM
• Cost, Cure, Survivorship, QOL
• Goals – sCR, MRD
• Immuno-Onc / Vaccines
• Side Effects & Supportive Care
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
Steroid S/E
• Mental
• irritability
• mood swings
• depression
• Insomnia
• General
• weight gain
• increased appetite
• general body swelling
• flushing, and sweating
• muscle cramping
• Glucose
• GI - heartburn, gas, and taste changes
• changes in sexual function
• and a “letdown” effect when steroids are stopped suddenly
• paradoxical fatigue
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
Bone
• Multiple myeloma is the most frequent
cancer to involve the skeleton, with up
to 80 percent of patients having bone
disease.
• Although fewer patients appear to have
bone involvement more recently, it is still
a major source of both complications
and death among patients with
myeloma.
Bone
• Low bone mass – osteopenia or
osteoporosis
• Lytic bone lesions
• Pain
• Pathologic fractures
• ONJ – osteonecrosis of the jaw from
bisphosphonate therapy
Bone - Zoledronic Acid in MM
UK 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 (2011;12:743-751)
Lancet 2010;376:1989-99
Bone
• Bisphosphonates
• inhibit the activity and formation of bone-destroying cells.
• pamidronate (Aredia)
• zoledronic acid (Zometa)
• 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)
• RANK Ligand Inhibitor
• Xgeva (denosumab, Amgen)
Infection
• MM results (usually) in the expansion in
one (mono-) type “clone” (-clone) =
monoclonal (M-spike) of Ig
• From MM -- Other Ig’s can be reduced
• Tx can reduce immunity
• Most common cause of MM death is
infection
• Augustson et al. JCO 2005 - 45% of early
deaths in MM were due to infections, primarily
pneumonia and sepsis
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
Infection
• IVIg considered
• Vax – PVX, Influenza
• lower Ab response, but still advised
• Thompson et al study – 2014-2015
• Px for high dose Dex
• PCP, herpes, antifungal
• Px for bortezomib
• Herpes zoster px
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
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/symptoms.html
• Anemia – consider Epo (VTE risk), RBC Tx
• Poor sleep
• Decr caffeine
• Good sleep hygiene
• Pain control
• Exercise / Cancer rehab consult
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
Sexual Side Effects
• Danish researchers recently found that patients who
underwent SCT frequently experienced sexual
dysfunction, sometimes for extended periods of time
after transplantation.
• Patients who experienced reduced sexual function
also reported lower quality of life.
• 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-ofsexual-dysfunction-after-stem-cell-transplantation/
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
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)
Neuropathy
• MM (before Tx)
• Tx related
• Thalidomide
• Much less with other IMiDs
• Bortezomib
• Less with SQ and/or qWK dosing
• not used much now
• Vincristine
• Platinums
Neuropathy
Mechanism (Thalidomide)
Thalidomide
• Researchers looked at MM pts (n=27 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
• Bilińska M et al. Pol Merkur Lekarski. 2011 Aug;31(182):86-91.
Neuropathy
Bortezomib Dosing
• FDA approved
• 1.3 mg/m2 IV d1,8,11 q21d
• PN 36% total ; Gr 3 7%, Gr 4 <1%
• Weekly
• 1.6 mg/m2 IV weekly
• REF: Greco et al. ASCO 2006 #7547
• N=37 (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
• N=222 (145 SQ, 77 IV) ; 3 RCT
• PN: SQ 38% vs. IV 53% (total)
• PN >=gr3 – SQ 57% vs. IV 70%
NOTE: No data for SQ qWEEK. SQ may be good for home. Weekly decr PN
Neuropathy
• There are no randomized controlled published studies 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
• Craig Hoffmeister (OSU):
• Finally the most important thing about peripheral neuropathy is to prevent it
before it happens. How can this be done? Critically patients must communicate
with their doctors about tingling, numbness, or burning in the hands or feet as the
doctor can then make a dose adjustment in the chemotherapy and prevent the
neuropathy from getting any worse. Yes, this means the drugs won't be as
effective, but it also means that the patient sometimes doesn't get saddled with
painful neuropathy for the rest of his/her life.
Neuropathy Treatments
Not proven
http://www.myelomabeacon.com/forum/preventing-peripheral-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
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"
Neuropathy
Other potential Therapies
• Massage
• Accupuncture
ASCO – Cancer.Net – Managing
Peripheral Neuropathy
• http://www.cancer.net/patient/All+About+Cancer/Cancer.Net+Featu
re+Articles/Side+Effects/Managing+Peripheral+Neuropathy
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
Financial toxicity
• Household finances
• Health Insurance
• Applying for insurance or filing claims can
•
•
be a full time job
Financial counselors
LLS
• Rights in the workplace
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/getinformationsupport/financialmatters/
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
Digestive / GI
• Constipation
• Pain meds
• Drugs (bortezomib)
• Hypercalcemia
• Diarrhea
• Nausea of Vomiting
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Cardiovascular
Renal
2nd malignancies
Cardiovascular / #CardioOnc
• Heart SE – decreased ejection fraction
• Anthracyclines
• Adriamycin – not used much
• Doxil – liposomal anthracycline – limited use
• SOB – Velcade, Carfzilzomib
• VRd vs. CfzRd – E1A11 substudy
• Consider cardiac amyloidosis - screening?
RTP ASH13
EAOnc 6-2014
Cardiovascular
• VTE – PE or DVT
• Esp assoc with Thal, Len/Dex
• Px
• ASA –
• Warfarin – INR 2.0-3.0
• LMWH
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
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)
Renal Dysfunction
•
•
•
•
•
•
Maintain hydration to avoid renal failure
Avoid use of NSAIDs
Avoid IV contrast
Plasmapharesis (NCCN cat 2B)
Not a contraindication to transplant
Monitor for renal dysfunction with chronic
use of bisphosphonates
Renal Failure Treatment
Bortezomib
•
•
•
•
Subset analysis of SUMMIT & CREST
S/E – similar in normal vs decr CrCL
Crt level not affected
Response
CrCL (mL/min)
n
ORR (%)
>80
105
45
51-80
99
33
<= 50
52
25
< 30
10
30
Jagannath et al. Cancer 2005;103:1195-1200
Renal Failure Treatment
• Bortezomib
• FDA approved in renal insuff/failure
• VD
• VTD
• VAD – Vincristine/Adriamycin/Dex
• thalidomide
• lenalidomide possible – PrECOG study
Renal Recovery
Reversibility of Renal Failure in Newly Diagnosed Patients with
Multiple Myeloma and the Role of Novel Agents
• group A: n=28 conventional chemo (CC) + Dexa-based
regimens (VAD, VAD-like regimens, melphalan plus Dexa);
• group B: n=38 - IMiDs-based regimens (thalidomide or
lenalidomide with high dose Dexa and/or CTX or melphalan)
• group C: n=16 - bortezomib-based regimens with Dexa
• A/B/C – Renal CR: 43% / 50% / 69% (p=0.2)
• A/B/C - RCR+RPR: 50% / 57% / 81% (p=0.1)
Roussou et al. ASH 2009 Abstr#955
Renal Recovery
• In multivariate analysis bortezomib–based regimens (p=0.02, OR:
7, 95% CI 1.5-25) and CrCl>30 ml/min (p=0.002, OR: 6.1, 95% CI 2.522.5) were independently associated with a higher probability of
RCR+RPR
• 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 Abstr#955
Outline
Side Effects
•
•
•
•
•
•
•
•
•
•
•
Steroid SE
Bone
Infection
Fatigue
Sexual
Neuropathy
Financial toxicity
Digestive / GI
Cardiovascular
Renal
2nd malignancies
2nd Malignancies in MM
http://www.ascopost.com/articles/august-15-2011/second-primary-malignancies-explored-in-multiple-myeloma.aspx
~2% inc SPM with Len added
SPM may not be MM specific…
CLL
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 (SIR=2.17,
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 (SIR=7.74, 95% CI=6.85, 8.72).
The risk of melanoma increased at younger ages, but was constant across >9 years of follow-up.
CLL patients also had an increased risk of death because of melanoma (SMR=4.79, 95% CI=3.83, 5.90) and nonmelanoma skin cancer (NMSC; SMR=17.0, 95% CI=14.4, 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)
Questions?
Cancer Dot Net
Survivorship
• http://www.cancer.net//survivorship
Prophylaxis
• Viral
• Bacterial
• +/- PCP – bactrim
• Immunizations
• Fluids, NSAID avoidance
• Bone – zoledronic acid
