Title: Survivorship, Patient Engagement
1Survivorship, 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
2Outline
- COI / Participatory Medicine
- Resources
- MMSM Twitter Chat
- What is a Survivor
- Side Effects Management
3Outline
- COI / Participatory Medicine
- Resources
- MMSM Twitter Chat
- What is a Survivor
- Side Effects Management
4Potential 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.
6Patient 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
7Outline
- COI / Participatory Medicine
- Resources
- MMSM Twitter Chat
- What is a Survivor
- Side Effects Management
8The 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
9Resources
- 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/
10National Coalition for Cancer Survivorship (NCCS)
- http//www.canceradvocacy.org/toolbox/multiple-mye
loma/ - Cancer Survival Toolbox
- Side Effects And Symptom Management
11Outline
- COI / Participatory Medicine
- Resources
- MMSM Twitter Chat
- What is a Survivor
- Side Effects Management
12Myeloma 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
13Outline
- COI / Participatory Medicine
- Resources
- MMSM Twitter Chat
- What is a Survivor
- Side Effects Management
14What is a Survivor?
15Survivorship 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
16Many 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
17The 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
18Curability 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.
19MM 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
20Mayo MM Survival
21MM 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
22I Will Survive
23OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
24Side Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
25Steroid 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
26Diabetes Mellitus
- Avoid (relatively) the following
- Dex
- Thal/Dex
- Len/Dex
- Bortezomib/Dex
- Bortezomib - hypoglycemia
27Sleep-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
28OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
29Bone Disease
- 80 MM Pts with bone disease depends on how
you look - A major source of
- pain
- complications
- death
30Bone
- Low bone mass osteopenia or osteoporosis
- Lytic bone lesions
- Pain
- Pathologic fractures
- ONJ osteonecrosis of the jaw from
bisphosphonate (or d-mab) Rx
31Bone - 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
32Bone - 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
33NCCN 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.
34NCCN 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)
35Bone
- OsteoCLASTs - bone-destroying cells
- OsteoBLASTs - bone-forming cells
- Treatments for bone disease include
- Drugs
- Radiation
- Vertebro- or kyphoplasty
- Surgery (less common now)
36Bone
- 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)
37Side Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
38Infection
- 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
39Infection
- 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
40Side Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
41Fatigue
- 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
42OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
43Sexual 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/
44OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
45Neuropathy
- 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)
47Neuropathy
- MM (before Tx)
- Tx related
- Thalidomide
- Much less with other IMiDs
- Bortezomib
- Less with SQ or qWK dosing
- not used much now
- Vincristine
- Platinums
48NeuropathyMechanism (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.
49Neuropathy 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
50Neuropathy
- 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) ?
51Effect 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
53Neuropathy 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
54Neuropathy 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"
55Neuropathy
- 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
56OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
57Financial 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
58Financial 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/
59OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
60Digestive / GI
- Constipation
- Pain meds
- Drugs (bortezomib)
- Hypercalcemia
- Diarrhea
- Nausea / Vomiting
61OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Cardiovascular
- Renal
- 2nd malignancies
62Cardiovascular 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
63Pt with thrombosis risk
- Avoid the following
- thalidomide
- bevacizumab (eg, Bev/Rev/Dex)
- Above Epo
64OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
65Renal 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)
66Renal 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
67Renal 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
68Renal 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 -
69Renal 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
70Renal 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
71Orlowski tweet
- MD Anderson trial for relapsed/refractory
myeloma patients with renal failure
Pomalidomide/Dex 1.usa.gov/UZuvW6.
1-855-MYELOMA.
72OutlineSide Effects
- Steroid SE
- Bone
- Infection
- Fatigue
- Sexual
- Neuropathy
- Financial toxicity
- Digestive / GI
- Cardiovascular
- Renal
- 2nd malignancies
732nd 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(No Transcript)
76MDS 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.
77SPM 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)
78Conclusions
- More Treatments
- Improved Survival
- More survivors
- Online, LLS resources
- MMSM Twitter Chat Sun 10/20 9-10pm
- WI has great myeloma people
79(No Transcript)
80Contact Info
- Aurora 414-219-4763
- Twitter _at_mtmdphd
81(No Transcript)
82SPMBiRD 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.
83MM 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
84MM 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
85Historical MM Tx
- 1960s
- Melphalan
- Glucocorticoids (steroids)
- 1970s-1980s
- Combo chemo VAD
- High dose chemo
- Stem cell transplant (SCT)
86Historical MM Tx
- 1990s
- bisphosphonates
- 2000-Present new drugs!
- thalidomide
- bortezomib
- lenalidomide
- bortezomib/Doxil (liposomal adriamycin) (rel/ref)
- Others
87LinkedIn 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