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Understanding Myeloma to Provide Optimal Patient Care (for Healthcare Providers) Understanding Myeloma to Provide Optimal Patient Care (for Healthcare.

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Presentation on theme: "Understanding Myeloma to Provide Optimal Patient Care (for Healthcare Providers) Understanding Myeloma to Provide Optimal Patient Care (for Healthcare."— Presentation transcript:

1 Understanding Myeloma to Provide Optimal Patient Care (for Healthcare Providers) Understanding Myeloma to Provide Optimal Patient Care (for Healthcare Providers) LLS WI MM Conference Sept 13, 2014 Mike Thompson, MD, - #mmsm Medical Director, Early Phase Cancer Research Co-PI Aurora NCORP Aurora Research Institute Aurora Health

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3 Potential Conflicts (or Convergence) of Interests: ECOG / NCI / ASCO ECOG-ACRIN MM Core Committee – ECOG-ACRIN MM Core Committee – NCI MM Steering Committee – NCI MM Steering Committee – ASCO ASCO Cancer Education Comm on Lymphoma & Plasma Cell Disorders

4 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 – Xconomy Advisor Xconomy Advisor #mmsm Myeloma Twitter Discussion Group Started 09/15/13

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6 Outline Other LLS MM 2014 Session Content Other LLS MM 2014 Session Content MM Background (Brief) MM Background (Brief) #MMSM Twitter Chat #MMSM Twitter Chat The New world of MM The New world of MM Cost, Cure, Survivorship, QOL Cost, Cure, Survivorship, QOL Goals – sCR, MRD Goals – sCR, MRD Immuno-Onc / Vaccines Immuno-Onc / Vaccines Side Effects & Supportive Care Side Effects & Supportive Care

7 Outline Other LLS MM 2014 Session Content Other LLS MM 2014 Session Content MM Background (Brief) MM Background (Brief) #MMSM Twitter Chat #MMSM Twitter Chat The New world of MM The New world of MM Cost, Cure, Survivorship, QOL Cost, Cure, Survivorship, QOL Goals – sCR, MRD Goals – sCR, MRD Immuno-Onc / Vaccines Immuno-Onc / Vaccines Side Effects & Supportive Care Side Effects & Supportive Care

8 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

9 Outline Other LLS MM 2014 Session Content Other LLS MM 2014 Session Content MM Background (Brief) MM Background (Brief) #MMSM Twitter Chat #MMSM Twitter Chat The New world of MM The New world of MM Cost, Cure, Survivorship, QOL Cost, Cure, Survivorship, QOL Goals – sCR, MRD Goals – sCR, MRD Immuno-Onc / Vaccines Immuno-Onc / Vaccines Side Effects & Supportive Care Side Effects & Supportive Care

10 Multiple Myeloma MM is a cancer of plasma cells MM is a cancer of plasma cells Plasma cells are highly differentiated B-cells Plasma cells are highly differentiated B-cells Many of the laboratory tests and clinical features are based on this unusual cell of origin Many of the laboratory tests and clinical features are based on this unusual cell of origin

11 MM Background Clinical Features Early MM – often asymptomatic Early MM – often asymptomatic Common clinical features: Common clinical features: C – hyper-Calcemia C – hyper-Calcemia R – renal (kidney) problems R – renal (kidney) problems A – anemia A – anemia B – bone pain B – bone pain Fatigue Fatigue Recurrent infections Recurrent infections Neuropathy Neuropathy

12 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 cases and deaths.

13 MM: New Cases vs. Age

14 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.

15 MM SEER Data Prevalence (2011): 83,367 in US 5yr OS ( ): 44.9% (2X 1985) 5yr OS ( ): 44.9% (2X 1985) Year Year Relative Survival 26.3%25.8%27.0%29.6%30.7%33.9%39.5%45.1%

16 More Myeloma Patients Longer Lives with MM Increasing MM incidence Increasing MM incidence Based on older age Based on older age Increasing MM prevalence Increasing MM prevalence Improved Rx and supportive care Improved Rx and supportive care Therefore MM optimization of care goals include disease control as well as QOL, cost/value, 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 More research into elderly Freiburg Comorbidity Index in 466 Multiple #Myeloma Patients & Combo w/ ISS Highly Predictive for Outcome #mmsmhttp://ow.ly/oO4T9

17 Survivorship "From the time of cancer diagnosis, through the balance of his or her life." "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 National Coalition of Cancer Survivorship & The Office of Cancer Survivorship (NCI) & Lance Armstrong Foundation

18 The “C” Word ASH 2009 ASH 2009 Bart Barlogie used the word “Cure” in talking about MM Bart Barlogie used the word “Cure” in talking about MM Ken Anderson (DFCI) & Vincent Rajkumar (Mayo) followed his talk and didn’t disagree Ken Anderson (DFCI) & Vincent Rajkumar (Mayo) followed his talk and didn’t disagree Usually talk about MM as an incurable disease Usually talk about MM as an incurable disease paradigm shift? paradigm shift?

19 MM Curability? (or chronic disease) Kathy Giusti Kathy Giusti Founder and CEO of the MM Research Foundation (MMRF) Founder and CEO of the MM Research Foundation (MMRF) 16 year multiple myeloma patient 16 year multiple myeloma patient Dx 1998 Dx 1998http://www.themmrf.org/about-the-mmrf/leadership/mmrf-founders.html

20 “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 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 Such favorable outcome with potential cure should be more likely with current programs associated with more frequent early intensive therapy and CR. Such favorable outcome with potential cure should be more likely with current programs associated with more frequent early intensive therapy and CR.

21 Outline Other LLS MM 2014 Session Content Other LLS MM 2014 Session Content MM Background (Brief) MM Background (Brief) #MMSM Twitter Chat #MMSM Twitter Chat The New world of MM The New world of MM Cost, Cure, Survivorship, QOL Cost, Cure, Survivorship, QOL Goals – sCR, MRD Goals – sCR, MRD Immuno-Onc / Vaccines Immuno-Onc / Vaccines Side Effects & Supportive Care Side Effects & Supportive Care

22 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 (MM- CT): 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/ ) One of those strategies included to: "...educate patients and providers about the significance of a new CT [clinical trial] using social media..."

23 #mmsm = MM Social Media Hashtag Folksonomy for Cancer Communities on Twitter Matthew S. Katz, MD – 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? “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. Twitter allows real-time interactions. Hashtags allow you to classify tweets, so that they can reach certain audiences. Hashtags allow you to classify tweets, so that they can reach certain audiences. It also permits tweetups, online meetups that can discuss pertinent issues. 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.” #bcsm has done this superbly and is enriching for the participating patients, advocates, caregivers, and providers.”

24 #mmsm Origin 1 year ago 08/29/13 – ASCO Connection Post Online Patient Communities for the E- Patient: “Betwixt and Between” a New Patient and an Expert Patient-Betwixt-and-Between-a-New-Patient-and-an-Expert.aspx 09/15/13 – First #mmsm Twitter Chat

25 #mmsm Topics #mmsm Topics Moderated DateTopicPeople 09/15/13Online Info, SMMRajkumar, Orlowski 10/20/13Induction; VRd vs CfRdKumar 11/16/13ECOG-ACRIN MtgThompson 01/26/14Allo SCT in MMHari 02/23/14Racial Disparities in MMRajkumar 03/16/14Clinical Trials in MMChmielewski 05/18/14Can we cure MM?Fonseca 06/29/14AmyloidosisWeiss 07/27/14MRDLandgren 08/24/14MM Risk AssessmentUsmani 09/07/14Crowdfunding for MM Research Ahlstrom

26 Crowdsourcing "...we must crowd-source the change we want to see in the world. Social media allows that to happen..." - in Bringing Social Media #Revolution to Health Care - Mayo Clinic Center for Social Media (#MCCSM)

27 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 #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,

28 Crowdsourcing Example Using social media, now positioned to: Using social media, now positioned to: Crowdsource innovative research ideas from the MM medical community Crowdsource innovative research ideas from the MM medical community Vet ideas with scientific advisory board Vet ideas with scientific advisory board Crowdvote for most interesting opportunities Crowdvote for most interesting opportunities Crowdfund for innovative ideas not funded by traditional research/trial funding sources Crowdfund for innovative ideas not funded by traditional research/trial funding sources

29 Crowdsourcing Presented by: Mike Thompson, MD, Medical Community Patient Community Oncologists/ Specialists/ Researchers Cooperative Research Groups FB Patient Groups FB Family/ Caregiver Groups Twitter Feeds Idea crowdsourcing Initial scientific vetting Idea crowdsourcing secondary input (Thalidomide Example) Crowd Voting/Ranking Process socialized via social media Short List Ideas Possible crowdfunding opportunities for early-stage not funded by traditional sources Patient Community Socialization

30 Myeloma Tweets Comparison of 2012 to 2013 MD Twitter use about cancer – linked to MD National Provider Identifier (NPI) Comparison of 2012 to 2013 MD Twitter use about cancer – linked to MD National Provider Identifier (NPI) 20% Increase 20% Increase Quadrupled MD conversations about multiple myeloma Quadrupled MD conversations about multiple myeloma NCI ECOG MM studies NCI ECOG MM studies Increased recognition Increased recognition Increased accrual (correlative, not nec causative) Increased accrual (correlative, not nec causative) Coordination b/w SWOG & ECOG for Coordination b/w SWOG & ECOG for ”U.S. Frontline Study” An analysis of cancer-specific Twitter conversations among physicians in et al. #ASCO14 Abstract e17644 ow.ly/xcxgz

31 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

32 #mmsm Suggested Topics?

33 Outline Other LLS MM 2014 Session Content Other LLS MM 2014 Session Content MM Background (Brief) MM Background (Brief) #MMSM Twitter Chat #MMSM Twitter Chat The New world of MM The New world of MM Cost, Cure, Survivorship, QOL Cost, Cure, Survivorship, QOL Goals – sCR, MRD Goals – sCR, MRD Immuno-Onc / Vaccines Immuno-Onc / Vaccines Side Effects & Supportive Care Side Effects & Supportive Care

34 “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?

35 Goals of Care? PFS PFS OS OS ORR ORR Lower ORR in Rd vs. RD but better OS Lower ORR in Rd vs. RD but better OS sCR after Auto SCT Kapoor et al. JCO Minimal Residual Disease (MRD) Minimal Residual Disease (MRD) Cure Cure And how defined? And how defined?

36 Role of SCT (beyond scope of my talk) Older Patients with Myeloma Derive Similar Benefit from Autologous Transplantation - Sharma et al. BBMT Importance of achieving stringent complete response (sCR) after autologous SCT in multiple myeloma.ow.ly/sZ980ow.ly/sZ980 Cost-effectiveness analysis of early v late auto SCT in multiple myeloma – Pandya et al. CPI-adjusted 2012 costs eASCT $ QALY 1.96 dASCT $ QALY 1.73 Prior studies showed no OS benefit of eASCT vs dASCT – Dunavin et al Leuke Lymphoma

37 Outline Other LLS MM 2014 Session Content Other LLS MM 2014 Session Content MM Background (Brief) MM Background (Brief) #MMSM Twitter Chat #MMSM Twitter Chat The New world of MM The New world of MM Cost, Cure, Survivorship, QOL Cost, Cure, Survivorship, QOL Goals – sCR, MRD Goals – sCR, MRD Immuno-Onc / Vaccines Immuno-Onc / Vaccines Side Effects & Supportive Care Side Effects & Supportive Care

38 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.

39 Vaccination in MM (1) 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

40 Vaccination in MM (2) Karlsson et al. - N=56 MM, WM, MGUS Poor vaccine response in multivariate analysis included hypogammaglobulinemia and concurrent chemotherapy ASH - Hahn - N=48 - Flu vax x1 = in 20-40% Ab response N=24 – Flu vax x2 – roughly double Ab response Whitaker et al. - Room for Improvement: Immuniz for Pts w/ Monoclonal B-Cell Lymphocytosis or CLL – so may be a B-cell cancer issue

41 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 San Francisco, CA. Abstract ID # Submitted. There is room to optimize vaccinations

42 Sample Collection Study 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

43 Survival curves for the overall population with and without the occurrence of Mayan doomsday. Wheatley-Price P et al. CMAJ 2012;184: ©2012 by Canadian Medical Association

44 Outline Other LLS MM 2014 Session Content Other LLS MM 2014 Session Content MM Background (Brief) MM Background (Brief) #MMSM Twitter Chat #MMSM Twitter Chat The New world of MM The New world of MM Cost, Cure, Survivorship, QOL Cost, Cure, Survivorship, QOL Goals – sCR, MRD Goals – sCR, MRD Immuno-Onc / Vaccines Immuno-Onc / Vaccines Side Effects & Supportive Care Side Effects & Supportive Care

45 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

46 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

47 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

48 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

49 Bone Multiple myeloma is the most frequent cancer to involve the skeleton, with up to 80 percent of patients having bone disease. 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. 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.

50 Bone Low bone mass – osteopenia or osteoporosis Low bone mass – osteopenia or osteoporosis Lytic bone lesions Lytic bone lesions Pain Pain Pathologic fractures Pathologic fractures ONJ – osteonecrosis of the jaw from bisphosphonate therapy ONJ – osteonecrosis of the jaw from bisphosphonate therapy

51 Bone - Zoledronic Acid in MM UK MRC Myeloma IX Data N = ~ 2000 MM Pts N = ~ 2000 MM Pts Zoledronic acid (Zometa) IV vs. oral (and less potent) cladronate (not avail in US) Zoledronic acid (Zometa) IV vs. oral (and less potent) cladronate (not avail in US) RESULTS – Favored Zometa RESULTS – Favored Zometa 50% fewer SRE 50% fewer SRE Improved OS 16% (incr med OS by 5.5 mon) Improved OS 16% (incr med OS by 5.5 mon) Increase PFS 12% (incr med PFS by 2.0 mon) Increase PFS 12% (incr med PFS by 2.0 mon) Lancet Oncology (2011;12: ) Lancet 2010;376:

52 Bone Bisphosphonates Bisphosphonates inhibit the activity and formation of bone-destroying cells. inhibit the activity and formation of bone-destroying cells. pamidronate (Aredia) pamidronate (Aredia) zoledronic acid (Zometa) zoledronic acid (Zometa) Bortezomib (Velcade) Bortezomib (Velcade) Transient rather than permanent new bone formation 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 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 New drugs – Not approved DKK-1 inhibitors DKK-1 inhibitors BHQ880 (Novartis) - antibody BHQ880 (Novartis) - antibody Activin A inhibitor Activin A inhibitor ACE-011 (Sotatercept, Acceleron/Celgene) [& anemia Tx?] ACE-011 (Sotatercept, Acceleron/Celgene) [& anemia Tx?] bone morphogenetic protein receptor type 1A (BMPR1A) inhibitor bone morphogenetic protein receptor type 1A (BMPR1A) inhibitor ACE-661 (Acceleron) ACE-661 (Acceleron) RANK Ligand Inhibitor RANK Ligand Inhibitor Xgeva (denosumab, Amgen) Xgeva (denosumab, Amgen)

53 Infection MM results (usually) in the expansion in one (mono-) type “clone” (-clone) = monoclonal (M-spike) of Ig 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 From MM -- Other Ig’s can be reduced Tx can reduce immunity Tx can reduce immunity Most common cause of MM death is infection Most common cause of MM death is infection Augustson et al. JCO % of early deaths in MM were due to infections, primarily pneumonia and sepsis

54 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

55 Infection IVIg considered IVIg considered Vax – PVX, Influenza Vax – PVX, Influenza lower Ab response, but still advised lower Ab response, but still advised Thompson et al study – Thompson et al study – Px for high dose Dex Px for high dose Dex PCP, herpes, antifungal PCP, herpes, antifungal Px for bortezomib Px for bortezomib Herpes zoster px Herpes zoster px

56 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

57 Fatigue “The most common symptom of multiple myeloma is fatigue, found in 70 percent of patients at diagnosis.” – Mayo “The most common symptom of multiple myeloma is fatigue, found in 70 percent of patients at diagnosis.” – Mayo Anemia – consider Epo (VTE risk), RBC Tx Anemia – consider Epo (VTE risk), RBC Tx Poor sleep Poor sleep Decr caffeine Decr caffeine Good sleep hygiene Good sleep hygiene Pain control Pain control Exercise / Cancer rehab consult Exercise / Cancer rehab consult

58 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

59 Sexual Side Effects Danish researchers recently found that patients who underwent SCT frequently experienced sexual dysfunction, sometimes for extended periods of time after transplantation. 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. Patients who experienced reduced sexual function also reported lower quality of life. Decreases in: Decreases in: sexual activity (38%) sexual activity (38%) ability to have sex (36%) ability to have sex (36%) pleasure from sex (31%), pleasure from sex (31%), interest in sex (28%) 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 - sexual-dysfunction-after-stem-cell-transplantation/

60 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

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

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

63 Neuropathy Mechanism (Thalidomide) Thalidomide Researchers looked at MM pts (n=27 MM & 30 ctrls) treated with thalidomide Researchers looked at MM pts (n=27 MM & 30 ctrls) treated with thalidomide clinical and electrophysiological assessment of peripheral sensory nerves clinical and electrophysiological assessment of peripheral sensory nerves axonal and demyelinating abnormalities axonal and demyelinating abnormalities Clinically: Clinically: arm and heat-pain detection thresholds were elevated arm and heat-pain detection thresholds were elevated threshold for skin cooling was decreased threshold for skin cooling was decreased Bilińska M et al. Pol Merkur Lekarski Aug;31(182): Bilińska M et al. Pol Merkur Lekarski Aug;31(182): Bilińska MPol Merkur Lekarski. Bilińska MPol Merkur Lekarski.

64 Neuropathy Bortezomib Dosing FDA approved FDA approved 1.3 mg/m2 IV d1,8,11 q21d 1.3 mg/m2 IV d1,8,11 q21d PN 36% total ; Gr 3 7%, Gr 4 <1% PN 36% total ; Gr 3 7%, Gr 4 <1% Weekly Weekly 1.6 mg/m2 IV weekly 1.6 mg/m2 IV weekly REF: Greco et al. ASCO 2006 #7547 REF: Greco et al. ASCO 2006 #7547 N=37 (26 evaluated) N=37 (26 evaluated) PN 0% PN 0% Subcutaneous (SQ) Subcutaneous (SQ) 1.3 mg/m2 SQ d1,4,8,11 q mg/m2 SQ d1,4,8,11 q21 REF: Moreau et al. Lancet Oncol 12(5): REF: Moreau et al. Lancet Oncol 12(5): N=222 (145 SQ, 77 IV) ; 3 RCT N=222 (145 SQ, 77 IV) ; 3 RCT PN: SQ 38% vs. IV 53% (total) PN: SQ 38% vs. IV 53% (total) PN >=gr3 – SQ 57% vs. IV 70% PN >=gr3 – SQ 57% vs. IV 70% NOTE: No data for SQ qWEEK. SQ may be good for home. Weekly decr PN

65 Neuropathy There are no randomized controlled published studies of any drug or supplement in myeloma patients looking to prevent or treat peripheral 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, Vitamin B6 and nutritional supplements with amino acids, pain medicines, anti-depressants, NSAIDs (watch kidneys!) anti-depressants, NSAIDs (watch kidneys!) Neuropathy meds – anti-seizure drugs Neuropathy meds – anti-seizure drugs Craig Hoffmeister (OSU): 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. 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.

66 Neuropathy Treatments Not proven 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 IU daily 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 IU daily

67 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" 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"

68 Neuropathy Other potential Therapies Massage Massage Accupuncture Accupuncture ASCO – Cancer.Net – Managing Peripheral Neuropathy re+Articles/Side+Effects/Managing+Peripheral+Neuropathy re+Articles/Side+Effects/Managing+Peripheral+Neuropathy re+Articles/Side+Effects/Managing+Peripheral+Neuropathy re+Articles/Side+Effects/Managing+Peripheral+Neuropathy

69 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

70 Financial toxicity Household finances Household finances Health Insurance Health Insurance Applying for insurance or filing claims can be a full time job Applying for insurance or filing claims can be a full time job Financial counselors Financial counselors LLS LLS Rights in the workplace Rights in the workplace

71 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. 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.Patient Financial Aid ProgramPatient Financial Aid Program 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. 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.Co-Pay Assistance ProgramCo-Pay Assistance Program Information and resources regarding insurance, managed care and employment issues are provided in Insurance and Employment. Information and resources regarding insurance, managed care and employment issues are provided in Insurance and Employment.InsuranceEmploymentInsuranceEmployment

72 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

73 Digestive / GI Constipation Constipation Pain meds Pain meds Drugs (bortezomib) Drugs (bortezomib) Hypercalcemia Hypercalcemia Diarrhea Diarrhea Nausea of Vomiting Nausea of Vomiting

74 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

75 Cardiovascular / #CardioOnc Heart SE – decreased ejection fraction Heart SE – decreased ejection fraction Anthracyclines Anthracyclines Adriamycin – not used much Adriamycin – not used much Doxil – liposomal anthracycline – limited use Doxil – liposomal anthracycline – limited use SOB – Velcade, Carfzilzomib SOB – Velcade, Carfzilzomib VRd vs. CfzRd – E1A11 substudy VRd vs. CfzRd – E1A11 substudy Consider cardiac amyloidosis - screening? Consider cardiac amyloidosis - screening? RTP ASH13EAOnc

76 Cardiovascular VTE – PE or DVT VTE – PE or DVT Esp assoc with Thal, Len/Dex Esp assoc with Thal, Len/Dex Px Px ASA – ASA – Warfarin – INR Warfarin – INR LMWH LMWH

77 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

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

79 Renal Dysfunction Maintain hydration to avoid renal failure Maintain hydration to avoid renal failure Avoid use of NSAIDs Avoid use of NSAIDs Avoid IV contrast Avoid IV contrast Plasmapharesis (NCCN cat 2B) Plasmapharesis (NCCN cat 2B) Not a contraindication to transplant Not a contraindication to transplant Monitor for renal dysfunction with chronic use of bisphosphonates Monitor for renal dysfunction with chronic use of bisphosphonates

80 Renal Failure Treatment Bortezomib Subset analysis of SUMMIT & CREST Subset analysis of SUMMIT & CREST S/E – similar in normal vs decr CrCL S/E – similar in normal vs decr CrCL Crt level not affected Crt level not affected Response Response CrCL (mL/min)nORR (%) > <= < Jagannath et al. Cancer 2005;103:

81 Renal Failure Treatment Bortezomib Bortezomib FDA approved in renal insuff/failure FDA approved in renal insuff/failure VD VD VTD VTD VAD – Vincristine/Adriamycin/Dex VAD – Vincristine/Adriamycin/Dex thalidomide thalidomide lenalidomide possible – PrECOG study lenalidomide possible – PrECOG study

82 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 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 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 group C: n=16 - bortezomib-based regimens with Dexa A/B/C – Renal CR: 43% / 50% / 69% (p=0.2) A/B/C – Renal CR: 43% / 50% / 69% (p=0.2) A/B/C - RCR+RPR: 50% / 57% / 81% (p=0.1) A/B/C - RCR+RPR: 50% / 57% / 81% (p=0.1) Roussou et al. ASH 2009 Abstr#955

83 Renal Recovery In multivariate analysis bortezomib–based regimens (p=0.02, OR: 7, 95% CI ) and CrCl>30 ml/min (p=0.002, OR: 6.1, 95% CI ) were independently associated with a higher probability of RCR+RPR In multivariate analysis bortezomib–based regimens (p=0.02, OR: 7, 95% CI ) and CrCl>30 ml/min (p=0.002, OR: 6.1, 95% CI ) 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. 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. 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

84 Outline Side Effects Steroid SE Steroid SE Bone Bone Infection Infection Fatigue Fatigue Sexual Sexual Neuropathy Neuropathy Financial toxicity Financial toxicity Digestive / GI Digestive / GI Cardiovascular Cardiovascular Renal Renal 2 nd malignancies 2 nd malignancies

85 2 nd Malignancies in MM

86 ~2% inc SPM with Len added

87 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 non- melanoma 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, (27 September 2011)

88

89 Questions?

90

91 Cancer Dot Net Survivorship

92 Prophylaxis Viral Viral Bacterial Bacterial +/- PCP – bactrim +/- PCP – bactrim Immunizations Immunizations Fluids, NSAID avoidance Fluids, NSAID avoidance Bone – zoledronic acid Bone – zoledronic acid


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