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
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