Multiple Myeloma in 2014: What Advanced Practice Providers Should Know November 2014 Scottsdale, Arizona Rochester, Minnesota Jacksonville, Florida Joseph Mikhael, MD, MEd, FRCPC Staff Hematologist, Mayo Clinic Arizona Objectives 1. Provide an overview of the types and spectrum of multiple myeloma 2. Discuss the “significance” of MGUS and its practical management 3. Review the diagnosis and staging of myeloma 4. Discuss the approach to therapy, including stem cell transplantation 5. Highlight the improvement in prognosis for patients with myeloma Myeloma case 68 yo male • 9 month history of low back pain • Treated by FP, PT, Chiropractor – no improvement • FP did plain x-rays, revealed multiple lytic lesions • Gradual increasing fatigue, SOBOE Case cont. • Hb 7.8, WBC 5.6, Plts 132 • Ca 10.8, Creat 1.6 • IgG Level 5800 (A and M depressed) • No Bence Jones proteinuria • Bone Marrow: 60% plasmacytosis • CRP normal, Albumin 3.4 • B2M elevated Case contd. • Does he have Myeloma? • What is your first step? • What to do about his hypercalcemia? • What to do about his anemia? • What to do about his bony disease? Epidemiology • 1% of malignancies • 10% of Heme cancers • 21000 Americans annually Epidemiology • Men > Women • Blacks > Whites • Median age of diagnosis is 66 • 10% < 50, 2% <40 Normal + - M-protein + - Pathophysiology • Malignant plasma cell dyscrasia • Accumulation of plasma cells in the bone marrow • These produce a single immunoglobulin (Ig) – monoclonal protein • Sequelae relate to presence of plasma cells or interactions they induce via cytokines in microenvironment The Plasma Cell Carr and Rodak: Clin Hematol Atlas The malignant clone IgM Lymph node Plasma cell somatic hypermutation lymphoblast plasmablast IgG,A,D,E plasma cell Bone Marrow pre-B cell How do plasma cells become “evil”? Immunoglobulins Mechanisms of Disease Progression in the Monoclonal Gammopathies Kyle, R. A. et al. N Engl J Med 2004;351:1860-1873 Molecular progression Normal plasma cell MGUS Translocations Infection Inflammation Asymptomatic Myeloma Active Myeloma ras & p53 mutation c-myc dysregulation Bone resorption Angiogenesis Aggressive Myeloma Del 13 Secondary translocations The Spectrum of Myeloma MGUS Organ damage none Marrow Disease <10% plasma cells Asymptomatic “True” MM PC MM Leukemia (smouldering) none yes yes ≥ 10% plasma ≥ 10% cells Management Monitor Close follow 1-2 up (q 3 mts) times/yr Transforma- 1% /yr 10-20%/yr tion rate plasma cells therapy n/a Plasma cells in blood Highdose combo chemo n/a MGUS Monoclonal Gammopathy of Unknown Significance • Presence of a serum monoclonal protein (concentration ≤ 3g/dL) • Less than 10% plasmacytosis in marrow • No evidence of End-Organ damage (CRAB) • Calcium elevation, Renal Insufficiency, Anemia, Bony disease • Asymptomatic • No co-existing plasma cell dyscrasia or lymphoproliferative disease (table) Diseases associated with a monoclonal gammopathy • Plasma cell disorders • Monoclonal gammopathy of undetermined significance • • • • • • • • • • • (MGUS) Biclonal gammopathy of undetermined significance Idiopathic Bence Jones proteinuria POEMS syndrome, Osteosclerotic myeloma Castleman's disease AL (light chain) amyloidosis Solitary plasmacytoma Multiple myeloma, Smoldering multiple myeloma B-cell lymphoproliferative disorders Non-Hodgkin's lymphoma Chronic lymphocytic leukemia Lymphoplasmacytic lymphoma (Waldenstrom macroglobulinemia) • Post-transplant monoclonal gammopathies Epidemiology • Prevalence is approximately 1-3% in adults in the USA, Sweden, France and Japan1 • Higher as we age: • ≥ 50: 3.2% • ≥ 70: 5.3% • ≥ 85: 7.5%2 • 2-3 fold higher incidence in Africans and African American population3 • Annual risk of transformation to MM or related diseases of 1%4 1 Kyle Blood 1972, Axelsson Acta Med Scan 1986, Saleun J Clin Path 1982, Iwanaga Mayo Clin Proc 2007; 2 Kyle NEJM 2006; 3 Singh J Lab Clin Med 1990, Cohen AM J Med 1998, Landgren Blood 2006; 4 Kyle et al NEJM 2002 Risk of Progression among 1384 Residents of Southeastern Minnesota in Whom Monoclonal Gammopathy of Undetermined Significance was Diagnosed in 1960 through 1994 Kyle R et al. N Engl J Med 2002;346:564-569 MGUS Progression • Potential Predictive Factors of Progression • M protein size1 • IG class: IgA>IgM>IgG2 • Bone marrow plasmacytosis3,4 • Presence of urinary Bence Jones proteinuria3 • Free Light Chain Assay5 1 Kyle NEJM 2002, 2 Kyle Blood 2003, 3 Cesana JCO 2002, 4 Perez-Persona Blood 2007 5 Rajkumar BJH 2004 Figure 3. Risk of progression of MGUS to myeloma or related disorder using a riskstratification model that incorporates the FLC ratio and the size and type of the serum monoclonal protein 20 year 58% 37% 21% 5% Rajkumar, S. V. et al. Blood 2005;106:812-817 Copyright ©2005 American Society of Hematology. Copyright restrictions may apply. Monitoring • No absolute consensus • Algorithm: • Make accurate diagnosis • Obtain baseline bloodwork (incl total Igs and FLC), 24 hr urine and skeletal survey • Repeat testing (history, physical, blood work only) at 6 months • If lower risk, can be seen annually (assuming asymptomatic) • If higher risk, I prefer every 6 months Bone Marrow Diagnosis of Myeloma The diagnosis of Myeloma is made as a result of several tests: 1. Blood Counts (CBC – white, red, platelets) 2. Blood and urine tests for immune proteins – IgG, IgA, IgM – total number (combination of normal protein and abnormal or “M” protein) – May also be “light chains” which are component of abnormal protein – May require 24 hour urine collections Diagnosis of Myeloma contd. 3. Bone Marrow tests (aspirate and biopsy) – This looks for the % of plasma cells in the marrow – Also looks for abnormal cytogenetics of the plasma cells and FISH analysis 4. X-rays looking for osteopenia, lytic lesions and fractures (NOT a bone scan) possibly MRI of the spine 5. Other blood tests creatinine, calcium, albumin beta-2microglobulin Multiple Myeloma - Types • Subtypes of MM are determined based on the kind of abnormal protein IgG – 55% IgA – 25% IgD – 1-2% IgM – 1% Light Chain Disease only – 20% Non Secretors 1-2 % M spike in gamma region Multiple Myeloma • Unfortunately, MM is not a curable disease (yet!!) • Historically most people did not live for much more than 2 years… • However, the average survival is now at least 8 years • This has been a result of two key developments: 1. Autologous Stem Cell Transplant 2. Novel Drugs (thalidomide, bortezomib, lenalidomide, carfilzomib, pomalidomide) Myeloma Staging • Older system of Salmon-Durie staging • Not as useful anymore • Newer system of using 2 factors: • Albumin and Beta-2-microglobulin • It is “prognostic” for survival • Practically, there are 2 stages 1. Can wait and watch 2. Requires treatment Cytogenetics • These are the genes of the plasma cells (not the patient) • May indicate more about the biology of the disease • Most can be found at diagnosis, but others may be “acquired” later • Could well be the most “prognostic” tool in myeloma as it may separate “high risk” myeloma from standard risk Molecular Prognostic Model Survival probability 1.0 All others including t(11;14) P<0.001 0.8 D13 Poor Intermediate Good 0.6 0.4 24.7 mos 42.3 mos 51.0 mos t(4;14) t(14;16) -17p13 0.2 0.0 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 Months Fonseca et al Blood 101:4569, 2003 Myeloma Treatment Principles of therapy 1. Stop the production of the abnormal plasma cells (chemo) 2. Strengthen the bone and prevent fractures 3. Increase the hemoglobin count and reduce fatigue 4. Reduce risk of infections 5. Promote well being and quality of life Treatment with Chemotherapy • Goal is to reduce the number of plasma cells and the proteins they produce • Timing is important as it may be possible to wait & watch • It is not “curative” but may put the disease into remission • Must be tailored to individual based on disease factors (type, severity, organs involved) and patient factors (age, general health…) Managing myeloma: the components Transplant Eligible Patients Consolidation Maintenance Initial Therapy Transplant Ineligible patients Treatment of Relapsed disease Consolidation/ Maintenance/ Continued therapy Supportive Care mSMART Mayo Stratification for Myeloma And Risk-adapted Therapy Newly Diagnosed Myeloma Website: www.msmart.org mSMART 2.0: Classification of Active MM High-Risk FISH Del 17p t(14;16) t(14;20) GEP High risk signature Intermediate-Risk* FISH t(4;14)‡ Cytogenetic Deletion 13 or hypodiploidy PCLI >3% Mikhael et al Mayo Clinic Proceedings April 2013 Standard-Risk*† All others including: Hyperdiploid t(11;14)** t(6;14) mSMART 2.0: Classification of Active MM High-Risk 20% FISH Del 17p t(14;16) t(14;20) GEP High risk signature 3 years Intermediate-Risk 20% FISH t(4;14)* Cytogenetic Deletion 13 or hypodiploidy Standard-Risk 60% All others including: Hyperdiploid t(11;14) t(6;14) PCLI >3% 4-5 years 8-10 years mSMART – Off-Study Transplant Eligible High Risk Intermediate Risk Standard Risk 4 cycles of VRd 4 cycles of CyBorD 4 cycles of Rda or CyBorD Collect Stem Cellsb Autologous stem cell transplant, especially if not in CR V or VCd for minimum of 1 year Autologous stem cell transplant Autologous stem cell transplant Bortezomib based therapy for minimum of 1 year a Bortezomib containing regimens preferred in renal failure or if rapid response b If age >65 or > 4 cycles of Rd Consider G-CSF plus cytoxan or plerixafor needed 2 cycles of Rd consolidation; Then Len maintenance if not in VGPR and Len responsive* Continue c Rd; or CyBorD for ~12 months c Continue Rd for patients responding to Rd and with low toxicities; Dex is usually discontinued after first year * Consider risks and benefits; consider limited duration 12-24 months Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110; Mikhael et al. Mayo Clin Proc 2013;88:360-376. v11 //last reviewed Dec 2013 mSMART – Off-Study Transplant Ineligible High Risk Intermediate Risk Standard Risk* VRd* for ~12 months, MP + weekly Bortezomib or weekly CyBorD for ~12 months Rda, b Continue VRd as maintenance for minimum of 1 year Bortezomib based therapy for minimum of 1 year a Dex is usually discontinued after first year Bortezomib containing regimens preferred in renal failure or if rapid response needed *Clinical trials strongly recommended as the first option b Dispenzieri et al. Mayo Clin Proc 2007;82:323-341; Kumar et al. Mayo Clin Proc 2009 84:1095-1110; Mikhael et al. Mayo Clin Proc 2013;88:360-376. v11 //last reviewed Dec 2013 Initial Response • Please note that the ultimate goal is both • • • DEPTH and LENGTH of response Deepest response is “Complete” Remission (=CR) vs partial remission or minimal remission It appears that a deeper response (esp CR) may predict a longer remission and even survival HOWEVER, trends do not predict any individual patient • We treat the patient not the disease Treatment sequence Front line treatment Induction VAD DEX Consolidation SCT Maintenance Maintenance Nothing Prednisone Thalidomide Relapsed Rescue Few options Treatment sequence NEW Thal/Dex VD Rev/Dex CyBorD VTD VRD SCT VD/VRD Front line treatment Induction OLD VAD DEX Consolidation SCT Nothing Thalidomide? Bortezomib? Lenalidomide? Maintenance Post consolidation Nothing Prednisone Thalidomide Bortezomib Lenalidomide Thalidomide Carfilzomib Pomalidomide Elotuzumab HDAC Bendamustine Monoclonal Antibodies Relapsed Rescue Few options IMPACT OF NOVEL THERAPY 2012/2013 Median 7.3 years 5 YEAR SURVIVAL BY AGE AGE AGE ≤ 65 YRS > 65 YRS 2012 ASH Abstract #3972 Kumar et al 2006-2010 73% 56% 2001-2005 63% 31% Long-Term Survival With CyBorD Induction Therapy In Newly Diagnosed Multiple Myeloma Craig B. Reeder, MD, Donna E. Reece, MD, Vishal Kukreti, MD, FRCPC, Joseph Mikhael, MD, Christine I. Chen, MD, Suzanne Trudel, MD, Kristina Laumann, Joseph Hentz, Giovani Piza, Rafael Fonseca, MD, P. Leif Bergsagel, MD, Jose F Leis, MD, PhD, Rodger E. Tiedemann, MBChB, PhD, FRACP, FRCPA, Jacy Spong, BS, RN, BSN, Angela Mayo, PA/NP and Keith Stewart, MD Reeder C. et al.; ASH 2013: abstract 3192 Results - Response ITT ORR CR / nCR Cohort 1 88% (29/33) 36% (12/33) Cohort 2 90% (27/30) 47% (14/30) All (n=63) 89% (56/63) 41% (26/63) >VGPR 61% (20/33) 63% (19/33) 62% (39/63) Cohort 1 Cohort 2 All (n=55) 96% (27/28) 46% (13/28) 93% (24/27) 48% (13/27) 93% (51/55) 47% (26/55) 71% (20/28) 63% (17/27) 67% (37/55) After 4 cycles ORR CR / nCR >VGPR Reeder C. et al.; ASH 2013: abstract 3192 Results - Survival Progression Free Survival (5 yr) Overall Survival (5 yr) ALL (n=63) 42% (95% CI:31-57) 70% (95% CI: 59-82) Standard Risk (n=39) 48% (95% CI: 33-69) 81% (95% CI: 69-95) High Risk (n=24) 33% (95% CI: 19-59) 54% (95% CI: 37-78) Most patients underwent auto stem cell transplant after completing the induction trial and most did not utilize maintenance therapy post SCT. Reeder C. et al.; ASH 2013: abstract 3192 LONG-TERM SURVIVAL WITH CYBORD: ASH 20131 OS by Risk Status OS: All Patients 1 ASH Abstract #3192 Reeder et al OS 81% at 5 years for standard risk The “NEW” CyBorD • All three drugs given weekly • Cyclophosphamide 300mg/m2 PO • Bortezomib 1.5 mg/m2 IV or SQ • Dexamethasone 40mg PO • We consider one cycle a 4 week course • No “week off” • Less neuropathy, more convenience, equal efficacy • Always give viral prophylaxis Retrospective, observational study: VCD and VRD as initial treatment for MM VCD (n= 101) Median age Mean treatment duration Pts undergoing ASCT VRD (n= 75) 62.7 years 60.9 years 5.1 5.4 months months 59% 50% Best response after 4 cycles 2-year PFS 2-year OS Common AEs reported in at least 3 treatment cycles Fatigue Peripheral Neuropathy Anemia GI 89% 66.6% 90.8% 81% 63.2% 87.4% 18% 11% 11% 9% 9% 16% 16% 8% Conclusion: Comparable outcomes with VCD and VRD in terms of response, PFS, OS and similar safety profiles Kumar et al. ASH 2013: Abstract 3178, poster presentation ASH 2012-3: Induction Regimens Response Rates (%) & Survival 1 Trial N nCR/sCR >=VGPR >=PR PFS OS CarCyDex 58 68 76 95 1-yr 86% 1 yr 85% CarLenDex 41 68 88 96 1 yr ≤ 83 NA CarThalDex1 50 18 60 92 1 yr 88% NA MLN9708-LenDex 65 23 58 90 1 yr 93% NA MLN9708-LenDex 64 24 67 96 NA NA CyCarThalDex 54 18 76 91 1 yr 90% 1 yr 98% R2V2 30 40 73 97 1 yr 97% 1 yr 100% Induction portion of CTD x 4 followed by HDM and consolidation with CTD x 4 Blood 120(21) 2012: Sonneveld Abs 333 Blood 122(21) 2013: Bringhen, Abs 685 Kumar Abs 332 Kaufman Abs 336: Len, Bortezomib, Dex, and Vorinostat Korde, Abs 538 Mikhael, Abs 3179 Richardson Abs 535 How Deep a Response Required before ASCT? Effect of Pre-transplant Salvage Therapy Prior to Autologous Transplant (ASCT) in Patients Not Responding to Initial Induction for MM Salvage Cohort Salvage Chemotherapy Diagnosis and Initial Induction Autologous Transplant < PR to induction No Salvage Cohort Autologous Transplant Diagnosis 12 months from diagnosis to ASCT Vij Blood 120(21) 2012, abstract 597 ASCT MM06-04-12_6.ppt Outcomes with/without Pre-ASCT Salvage PFS 100 OS 100 90 90 P = NS 80 P = NS 70 80 NO SALVAGE (n=251) 60 50 70 60 50 40 30 40 SALVAGE (n=324) SALVAGE (n=324) 30 20 20 NO SALVAGE (n=251) 10 0 0 2 4 6 Years Vij Blood 120(21) 2012, abstract 597 10 0 8 10 0 2 4 6 Years 8 10 Median follow-up Salvage No Salvage Months 61 (9-181) 68 (110-180) (Source: Txz12_23 & _24) MM06-04-12_15.ppt Stem Cell Transplant • Concept: eliminate any remaining abnormal plasma cells in the bone marrow with HIGH dose chemotherapy (ie what may be left after initial chemotherapy) • Process 1. Use initial chemotherapy to reduce plasma cells 2. Collect stem cells from bone marrow a. Mobilization with neupogen (G-CSF) +/- chemo b. Collection by pheresis in stem cell unit c. Storage of stem cells (frozen) 3. Admit and give high dose treatment (wipe out current marrow) 4. Re-Infuse stem cells previously collected and wait for them to “grow” ASCT Patient Priming Therapy Collect PBSCs High-dose Chemotherapy Reinfuse PBSCs +/- Post-ASCT therapy Freeze Autologous Stem Cell Transplantation: Timing • Most trials incorporate SCT as consolidation therapy after initial treatment • Trials comparing timing of transplant, as part of initial treatment or after relapse, show better disease free survival with initial SCT but equivalent overall survival • Currently there is some debate about the role of SCT when novel drugs are used for initial treatment Autologous Transplant Improves Responses after Traditional or Novel Induction Sonneveld JCO 12 Harrouseau JCO 10 Cavo Lancet 10 VAD BtzAD VAD BtzD ThalD BtzThalD Induction ≥nCR 5% 11% 7% 15% 11% 31% Transplant ≥nCR 15% 31% 18% 35% 31% 52% Transplant Ineligible FIRST Design: Lenalidomide and Low-dose Dexamethasone (Rd/Rd18) vs. MPT n=535 Arm B Rd18 n=541 LEN + Lo-DEX: 18 Cycles (72 wks) LENALIDOMIDE 25mg D1-21/28 Lo-DEX 40mg D1,8,15 & 22/28 MEL + PRED + THAL 12 Cycles1 (72 wks) Arm C MPT n=547 MELPHALAN PREDNISONE THALIDOMIDE 0.25mg/kg D1-4/42 2mg/kg D1-4/42 200mg D1-42/42 Subsequent anti-MM Tx ARM Arm AA LENALIDOMIDE 25mg D1-21/28 Rd N = 535 Lo-DEX 40mg D1,8,15 & 22/28 PD or Unacceptable Toxicity LEN + Lo-DEX until Progressive Disease RANDOMIZATION 1:1:1 LT Follow-Up Active Treatment + PFS Follow-up Phase PD, OS and Screening Pts > 75 yrs: Lo-DEX 20 mg D1, 8, 15 & 22/28; THAL2 100 mg D1-42/42, Melphalan2 0.2 mg/kg D1–4 n= 1,623 - 18 countries from North America, Asia-Pacific, and Europe represented from 246 Centers • Stratification: age, country and ISS stage International Staging System; LT, long-term; PD, progressive disease; OS, overall survival 1Facon T, et al. Lancet 2007;370:1209-18; 2Hulin C, et al. JCO. 2009;27:3664-70. Facon T. et._ASH 2013: Abstract 2 FIRST Trial: Final PFS Continuous Rd the risk of PFS events (PD or death) by 28% vs. MPT Median PFS 100 80 Rd (n= 535) 25.5 mos Rd18 (n= 541) 20.7 mos MPT (n= 547) 21.2 mos Hazard ratio Patients (%) Rd vs. MPT: 0.72; P = 0.00006 60 Rd vs. Rd18: 0.70; P = 0.00001 Rd18 vs. MPT: 1.03; P = 0.70349 40 72 wks 20 0 0 6 12 18 24 30 36 42 48 54 60 Time (months) Rd 535 400 319 265 218 168 105 55 19 2 0 Rd18 541 391 319 265 167 108 56 30 7 2 0 MPT 547 380 304 244 170 116 58 28 6 1 0 mos, months; MPT, melphalan, prednisolone, thalidomide; PFS, progression-free survival; Rd, Lenalidomide plus low-dose dexamethasone. Facon T. et._ASH 2013: Abstract 2 FIRST Trial: Overall Survival Interim Analysis 574 deaths (35% of ITT) 4-year OS 100 Patients (%) 80 Rd (n= 535) 59.4% Rd18 (n= 541) 55.7% MPT (n= 547) 51.4% 60 Hazard ratio 40 Rd vs. MPT: 0.78; P = 0.0168 ( 22% risk of death with Rd) Rd vs. Rd18: 0.90; P = 0.307 Rd18 vs. MPT: 0.88; P = 0.184 20 The pre-specified boundary (p<0.0096) was not crossed for Rd_continuous vs MPT_18 months 0 Rd Rd18 MPT 0 6 12 535 541 547 488 505 484 457 465 448 18 24 30 36 42 48 Overall survival (months) 433 425 418 403 393 375 338 324 312 224 209 205 121 124 106 43 44 30 54 60 5 6 3 0 0 0 Facon T. et._ASH 2013: Abstract 2 Relapsed Disease Treatment sequence NEW Thal/Dex VD Rev/Dex CyBorD VTD VRD SCT VD/VRD Front line treatment Induction OLD VAD DEX Consolidation SCT Nothing Thalidomide? Bortezomib? Lenalidomide? Maintenance Post consolidation Nothing Prednisone Thalidomide Bortezomib Lenalidomide Thalidomide Carfilzomib Pomalidomide Elotuzumab HDAC Bendamustine Monoclonal Antibodies Relapsed Rescue Few options Carfilzomib: A Novel Agent Designed to Promote Selective and Sustained Proteasome Inhibition • Carfilzomib is a next-generation, selective proteasome inhibitor • Potent and sustained target suppression • Improved antitumor activity • Minimal off-target activity with low neurotoxicity Tetrapeptide H N N O O O Adapted from: Kuhn DJ, et al. Blood. 2007;110:3281-3290. N H H N O Epoxyketone O O N H O 69 Neuropathy Was Infrequent and Not Dose Limiting Pooled data from single-agent studies (003 / 004 / 005) N=505 • Peripheral neuropathy occurred infrequently across all single-agent studies* • Only 6 patients (1.2%) experienced a Grade 3 PN event • No Grade 4 PN events Did not experience peripheral neuropathy • Only 1 patient had drug discontinued for PN (study 004; BTZ-treated arm) Grade 1/2 PN (13.4%) Grade 3 PN (1.2%) *Includes the terms peripheral neuropathy, neuropathy, peripheral sensory neuropathy, Adapted from: Singhal S, et al. ASH 2010. Abstract 1954 (poster presentation). peripheral motor neuropathy 70 Carfilzomib - Practical • Highly effective and very well tolerated • Beware of tumor lysis hence dosing schedule • Cardiac issue present but mostly mitigated by fluid management • Issues of weekly dosing being explored • Lack of neuropathy very attractive • Upfront uses increasing Molecular Structure of Thalidomide, Lenalidomide and Pomalidomide Structurally similar, but functionally different both qualitatively and quantitatively Myeloma Pomalidomide Summary Lacy Pom/Dex 1-3 reg Lacy Pom/Dex Len ref Richardson Pom+/- dex MM-002 PR 63% 32% 28% MR 82%* 47% 52% Median 3 prior regimens Median 4-6 prior regimens 73 Pomalidomide - Practical • Similar to lenalidomide with slightly less myelotoxicity and fatigue • Dosing range 2-4mg • Thromboprophylaxis necessary • Feasible in combination NEWER THERAPIES: ASH 2013 TOP 8 Anti-CD 38 monoclonal antibodies (MAb) daratumumab (abstracts #227 and #1986) and SAR 650984 (#284) MLN 9708 (ixazomib citrate: abstracts #535, 1944, and 1983) ARRY 520 (abstracts #285 and #1982) ACY-1215 (abstracts #759 and #3190) Selinexor (also known as KPT-330, abstract #279) Anti-CD 138 monoclonal antibody (BT062, indatuximab ravatansine, abstract #758) Panabinostat (abstract #1970) Bendamustine (abstract #1971) Conclusions • MGUS is a common condition that must be appropriately managed, including risk stratifying patients • Multiple Myeloma is an uncommon condition but has improved survival with use of novel agents and stem cell transplant • Newer agents are showing outstanding results with the recent additions of carfilzomib and pomalidomide • Although the mainstay of treatment is directed at the cancer itself, considerations must be given to supportive care and quality of life