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Relapsed and Refractory Myeloma Ruben Niesvizky Myeloma Center Myelomacenter.org

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1 Relapsed and Refractory Myeloma Ruben Niesvizky Myeloma Center Myelomacenter.org

2 Multiple Myeloma: Natural History of Disease Durie B; International Myeloma Foundation. Concise review of the disease and treatment options: multiple myeloma. 2011/2012 edition; Kumar SK, et al. Mayo Clin Proc. 2004;79: M-Protein Level MGUS or Indolent Myeloma Active Myeloma Remission Relapse Frontline Therapy Second- or Third- Line Therapy Remission duration decreases with each line of therapy // AsymptomaticSymptomaticRelapsing Refractory

3 Outline Approach to the patient with RRMM: – Evidence based – Factors to be considered in selecting therapy Proteasome inhibitors Inmunomodulatory Agents HDAC inhibitors Alkylating agents

4 Clinical Considerations for Relapsed/Refractory Disease Disease characteristics/prior therapy – Line of therapy – Plateau phase=quiescent period – Aggressiveness of relapse – Relapsed or relapsed and refractory disease –“ High risk disease ” – Prior therapies (eg SCT, prior IMiD, bortezomib- based therapy)

5 Clinical Considerations for Relapsed/Refractory Disease Disease characteristics/prior therapy – Line of therapy – Plateau phase=quiescent period – Aggressiveness of relapse – Relapsed or relapsed and refractory disease –“ High risk disease ” – Prior therapies (eg SCT, prior IMiD, bortezomib- based therapy)

6 Response Duration Decreases With Successive Therapies 578 patients; median age 65 years (follow up 55 months) Overall survival – One year 72% – Two years 55% – Three years 22% 84% died within five years Kumar SK, et al. Mayo Clin Proc. 2004;79:

7 APEX: Bortezomib Early or Late Relapse Bortezomib 1 prior therapy n = 132 > 1 prior therapy n = 200 Median TTP (months) CR (%)10%*7% † CR + PR (%)51%*37% † Median Duration of Response (months) year Survival89%73% * Evaluable patients, response to bortezomib after 1 prior therapy: n = 128 † Evaluable patients, response to bortezomib after >1 prior therapy: n = 187 Sonneveld P, et al. Haematologica. 2005;90: Abstract P ; Data on file; Millennium Pharmaceuticals, Inc.

8 Time to Progression Overall Survival 2 nd Line (LenDex) Median 17.1 months ≥ 3th line(LenDex) Median 10.6 months 2 nd Line (LenDex) Median 42 months ≥ 3th line(LenDex) Median 35.8 month Improved Outcomes with the Early Use of LenDex : TTP and OS Stadmauer EA et al. Eur J Haematol 2009; 82:426-32

9 Clinical Considerations for Relapsed/Refractory Disease Disease characteristics/prior therapy – Line of therapy – Plateau phase=quiescent period – Aggressiveness of relapse – Relapsed or relapsed and refractory disease –“ High risk disease ” – Prior therapies (eg SCT, prior IMiD, bortezomib- based therapy)

10 Kumar SK, et al. Bone Marrow Transplant. 2008;42: Time to Progression After SCT Correlates With OS After Initial Relapse

11 Clinical Considerations for Relapsed/Refractory Disease Disease characteristics/prior therapy – Line of therapy – Plateau phase=quiescent period – Aggressiveness of relapse – Relapsed or relapsed and refractory disease –“ High risk disease ” – Prior therapies (eg SCT, prior IMiD, bortezomib- based therapy)

12 Frontline vs Relapsed Refractory Response to Therapy Survival Outcomes Toxicities and Co-morbidities Response to Therapy Survival Outcomes Response to Therapy Survival Outcomes Treatment Naive Relapsed and Refractory High risk features Genomic instability

13 Relapsed /Refractory Outcomes in Relapsed and Refractory Multiple Myeloma Adapted from: Durie BGM. Multiple Myeloma. International Myeloma Foundation. 2011/2012 edition. Jagannath S. Clin Lymphoma Myeloma. 2008;8 Suppl 4:S149-S156. Relapsed Frontline Treatment Frontline Treatment Expected survival (months) Sensitivity to therapy Sensitive Treatment limitations/ comorbidities Peripheral neuropathy (~15% at diagnosis) Less Sensitive/Resistant >80% incidence of peripheral neuropathy Compromised marrow reserve Cytopenia 6-10 Resistant Intolerant to or ineligible for available therapy Elderly population (  risk for heart, lung, renal, liver dysfunction, diabetes)

14 Nature of Relapse How did the patient present? – 80% share clinical features with presentation Has been a shift on presentation? – Intact immunoglobulin to light chain only – Non-secretory relapse – Extra medullar disease

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16 Nature of Relapse How did the patient present? – 80% share clinical features with presentation 35% relapse both light chain and intact Ig 49.6% intact Ig 10% free light chain only

17 Survival according to paraprotein and FLC secretion at first relapse. Brioli A et al. Blood 2014;123: ©2014 by American Society of Hematology

18 Survival from relapse according to paraprotein and FLC secretion at relapse for patients with IgG and IgA paraproteins. Brioli A et al. Blood 2014;123: ©2014 by American Society of Hematology

19 Nature of Relapse How did the patient present? – 80% share clinical features with presentation 35% relapse both light chain and intact Ig 49.6% intact Ig 10% free light chain only Has been a shift on presentation? – Intact immunoglobulin to light chain only – Non-secretory relapse – Extra medullar disease

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21 Progression-free survival according to the presence of extramedullary (EM) involvement at diagnosis. Varettoni M et al. Ann Oncol 2009;21: © The Author Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please

22 Outcome according to baseline PET/CT. Zamagni E et al. Blood 2011;118: ©2011 by American Society of Hematology

23 Patient Heterogeneity

24 Clinical Considerations for Relapsed/Refractory Disease Toxicity considerations – Peripheral neuropathy – Thrombotic risk – Myelosuppression – Impact of prior therapies (eg, SCT, other cumulative toxicity)

25 ANY PROGRESS? Kumar et al. Blood Brenner et al. Blood Overall survival in 6-year intervals from time of diagnosis Time (months) Proportion of patients – – – – – – –1976

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27 Kumar et al: Leukemia Nov 2013 > 65 años < 65 años

28 Bortezomib Carflizomib Ixazomib Oprozomib Proteosome Inhibitors

29 Proteasome Inhibitors Outcomes Correlate with Depth of Response

30 Quality of Response: Survival Niesvizky et al., Br J Haematol Oct;143(1):46-53

31 Proteasome Inhibitors Benefits of Retreatment

32 Bortezomib Retreatment – A Retrospective Multicenter Survey Retrospectively collected data- multicenter non-interventional survey of pts who received bortezomib for a second time (retreatment) ► Patients: 65 pts,19 centers; median age 65 yrs Hrusovsky I, et al. ASH 2007, abstract #2720 ► Results: 49 evaluable (modified ITT) Bortezomib mg/m 2 Initial Re- treatment 1.394%86% 1.02%12% other8%4% + Dex39%61% Median 4 prior therapies Retreatment Initial bortezomib Diagnosis 52 mos Mean of 5 cycles Mean of 4 cycles 6 pts received additional therapy Best Response months Patients (n) Treatment Outcomes Safety: AE occurring in > 2 patients Retreatment Median % Patients Treatment received

33 Petrucci et al, Br J Haem 2013,160,

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35 Proteasome Inhibitors Carflilzomib

36 Carfilzomib IV on days 1, 2, 8, 9, 15 and 16 every 28 days 20 mg/m 2 in Cycle 1 and 27 mg/m 2 from Cycle 2 and beyond (maximum 12 cycles) Carfilzomib IV on days 1, 2, 8, 9, 15 and 16 every 28 days 20 mg/m 2 in Cycle 1 and 27 mg/m 2 from Cycle 2 and beyond (maximum 12 cycles) Study 003-A1: Open-Label Phase 2b Study of Single-Agent Carfilzomib in Relapsed and Refractory Multiple Myeloma (R/R MM) Primary endpoint: ORR IMWG response criteria (IRC assessed) Secondary endpoints CBR (ORR+ MR), DOR, OS, PFS, TTP, safety Siegel D, et al. Blood. 2012;120: Study Population (N=266) Relapsed from ≥2 prior lines of therapy Must include bortezomib Must include thalidomide or lenalidomide Refractory to last regimen CBR = clinical benefit rate; DOR = duration of response; IMWG = International Myeloma Working Group; IRC = Independent Review Committee; MR = minimal response; ORR = overall response rate; OS = overall survival; PFS = progression-free survival

37 Single-Agent Carfilzomib: Response Rates *IRC-determined; 11 patients had unconfirmed response Percentage of Patients ORR = 24% CBR = 37% DCR = 69% TTR: 1.9 mo (≥PR) and 1.0 mo (≥MR) DOR: 7.8 mo (≥PR) and 8.3 mo (≥MR) Subset analyses of higher risk populations showed similar response rates (e.g., unfavorable cytogenetics, baseline peripheral neuropathy) Siegel D, et al. Blood. 2012;120: N = 257 response- evaluable population CR = complete response; PD = progressive disease; PR = partial response; SD = stable disease; TTR = time to response; VGPR = very good partial response

38 Single-Agent Carfilzomib: PFS, OS Siegel D, et al. Blood. 2012;120: Proportion alive and without progression Months Median PFS = 3.7 mo (95% CI 2.8 – 4.6) Proportion surviving Months Median OS = 15.6 mo (95% CI 13.0 – 19.2) N = 257 response- evaluable population

39 39

40 Phase II Trial of Carfilzomib Plus Len/Dex in R/R MM (1-3 prior lines of therapy) Response (N = 52 pts receiving maximal planned dose)n (%) ORR Stringent CR CR VGPR PR SD 40 (77) 2 (4) 1 (2) 19 (37) 18 (35) 3 (6) Median duration of response, mos (range)22.1 ( ) Wang M, et al. Blood. 2013;122: Week 1Week 2Week 3Week 4: rest Carfilzomib 20/27 mg/m 2 IV* Dexamethasone 40 mg/d PO Lenalidomide d1-d21 25 mg/d PO D1/D2 D8/D9 D15/D16 D1D8D15D22 *20 mg/m 2 cycle 1 days 1 and 2 only, 27 mg/m 2 thereafter

41 Phase III ASPIRE Trial: Carfilzomib + Len/Dex vs Len/Dex in R/R MM (ongoing) Study Population (N=780) Measurable disease 1-3 prior regimens Relapse or PD Response to ≥ 1 prior regimen Exclusion factors: Bortezomib-refractory Len/dex-refractory Prior carfilzomib CRd Carfilzomib 27 mg/m 2 IV day 1, 2, 8, 9, 15, and 16 (20 mg/m 2 on days 1, 2 of cycle 1 only) Lenalidomide 25 mg Days 1-21 Dexamethasone 40 mg once weekly Rd Lenalidomide 25 mg Days 1-21 Dexamethasone 40 mg once weekly Stratify: Prior bortezomib, prior lenalidomide, β2 microglobulin level Primary endpoint: PFS Available at: Accessed April 29, day cycles Press release- PFS 26.3 vs 17.6 HR 0.69:

42 Phase 1b Study of High-Dose Carfilzomib + Dexamethasone in R/R MM Badros A, et al. ASH Abstract Study population: N=22 (expanded 007 cohort) Median prior regimens: 4 Regimen: (28-day cycles) Carfilzomib 20/45 or 20/56 mg/m min IV D1,2,8,9,15,16 Dexamethasone 20 mg D1,2,8,9,15,16 then 40 mg D22 Endpoint CFZ 20/45 CFZ 20/56 Total ORR, % CR, %000 VGPR, % PR, %43030 DORNR PFS, months Treatment-emergent Grade ≥3 AE, % CFZ 20/45 CFZ 20/56 Total Hematologic Thrombocytopenia Anemia Lymphopenia Nonhematologic Hypertension Hypophosphatemia Pneumonia Safety Efficacy CFZ = carfilzomib

43 Phase III ENDEAVOR: Carfilzomib + Dex vs Bortezomib/Dex in R/R MM 1 1.ClinicalTrials.gov. Available at: Accessed March 26, 2014.http://clinicaltrials.gov/ct2/show/NCT Vij R, et al. Blood. 2012;119: Study Population (N=888) Measurable disease Responsive to at least 1 prior therapy Relapsed following 1-3 prior treatment regimens ECOG PS 0-2 Cd Carfilzomib 20/56 mg/m 2 IV D1,2, 8, 9, 15, 16 Dexamethasone 20 mg PO or IV D1, 2, 8, 9, 15, 16, 22, day cycle Vd Bortezomib 1.3 mg/m 2 IV or SC D1, 4, 8, & 11 Dexamethasone 20 mg PO or IV D1, 2, 4, 5, 8, 9, 11, day cycle Treat until PD or unacceptable toxicity Stratify: Prior PI, prior lines of therapy, ISS, bortezomib IV vs. SC Primary endpoint: PFS Note use of higher carfilzomib dose—based on results from 004 trial, which suggested dose-response relationship of carfilzomib 2

44 Novel PIs Under Investigation in R/R MM Agent Status Ixazomib Two phase I studies showed activity of single-agent ixazomib [2,3] Oprozomib Phase 1 dose-escalation study showed some activity in patients with heavily pretreated hematologic malignancies, including MM [4] 1.Richardson PG, et al. ASH Abstract Lonial S, et al. ASCO Abstract Kumar S, et al. ASCO Abstract Savona MR, et al. ASH Abstract 203.

45 Ixazomib: Oral Proteasome Inhibitor

46 Ixazomib treatment duration and response. Kumar S K et al. Blood 2014;124: ©2014 by American Society of Hematology

47 Proteasome Inhibitors Oprozomib

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52 OPomDex Study Design (Phase 1b)

53 Bortezomib Carflizomib Ixazomib Oprozomib Thalidomide Lenalidomide Pomalidomide Proteosome Inhibitors Immunomodulating Agents

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55 Pomalidomide in Relapsed/Refractory Multiple Myeloma POM + LoDEX achieved responses in pts with prior LEN and/or BORT treatment, including those who are refractory 1-4 StudyPhaseNTreatmentPopulationMedian Prior Tx (Range)≥ PR Lacy POM: 2 mg (28/28-day cycle) Dex: 40 mg/week 1-3 prior Tx, relapsed/refractory 2 (1-3)65% 234 POM: 2 mg (28/28-day cycle) Dex: 40 mg/week LEN-refractory4 (1-14)32% 235 POM: 2 mg (28/28-day cycle) DEX: 40 mg/week LEN- and BORT- refractory 6 (3-9)26% 260 POM: 4 mg (28/28-day cycle) Dex: 40 mg/week 1-3 prior Tx, LEN- refractory 2 (1-3)37% 235 POM: 4 mg (28/28-day cycle) DEX: 40 mg/week LEN- and BORT- refractory 6 (2-11)29% Lacy MQ et al. Blood. 2011;118: Lacy MQ et al. Blood. 2011;118: Abstract Lacy MQ et al. J Clin Oncol. 2009;27: Lacy MQ et al. Leukemia. 2010;24:1934.

56 Pomalidomide Pts, n Median No. Prior Regimens Refractory to Recent Therapy (%)ORR (%) Pomalidomide ± dex  34 Pomalidomide, dex 2 706NR 26  29 Pomalidomide, dex  35 Pomalidomide, cyclophosphamide, prednisone 4 32 NR (1 to 3) 44 * 59 Pomalidomide, dex, clarithromycin 5 46 NR (at least 3) NR60 *Len specifically 4. Palumbo A et al. Blood. 2011;118. Abstract Mark TM et al. Blood. 2011;118. Abstract Vij R et al. J Clin Oncol. 2012;30. Abstract Lacy MQ et al. Blood. 2011;118: Leleu X et al. Blood. 2011;118. Abstract 812.

57 ClaPd: Study Design A single-center, phase 2 study of Clarithromycin combined with Pomalidomide + Low Dose Dexamethasone in RRMM p.o., orally; b.i.d., twice a day; RRMM, relapsed, refractory MM Day Dex 40mg PO Dex 40mg PO Dex 40mg PO Dex 40mg PO Dex 40mg PO Dex 40mg PO Dex 40mg PO Dex 40mg PO Pomalidomide 4 mg PO Clarithromycin 500mg PO BID

58 Clarithromycin???

59 Results 98 patients completed at least 1 cycle of ClaPD. – median number of cycles received was 6 (range 1–25) – median study follow-up was 9.6 months (range 1.0–25.6) In responding patients, median time to PR was 1 cycle (range 1–7). Median time to best response was 2 cycles (range 1-14). Best Response (IMWG Criteria) n (%)Overall (N = 98) ORR (≥ PR)56 (57) CBR (≥ MR)65 (66) sCR6 (6) VGPR 17 (17) PR33 (34) MR9 (9) SD 23 (23) PD 10 (10) IMWG, International Myeloma Working Group; CBR, clinical benefit rate; MR, minimal response; PD, progressive disease; sCR, stringent complete response; SD, stable disease.

60 Treatment History With Len/Bort Did Not Influence Response to ClaPD Best Response (IMWG Criteria) n (%)Overall (N = 98) Lenalidomide refractory (N = 83) Bortezomib Refractory (N = 82) Lenalidomide and bortezomib refractory (N = 72) ORR (≥ PR)56 (57)47 (63)46 (56)39 (54) CBR (≥ MR)65 (66)56 (67)54 (65)(65) sCR6 (6)6 (7)5 (6)5 (7) VGPR 17 (17)13 (16) 9 (13) PR33 (34)28 (34) 25 (35) MR9 (9)8 (10) 8 (11) SD 23 (23) 18 (22)19 (23)16 (22) PD 10 (10) 8 (12)9 (11)9 (13) IMWG, International Myeloma Working Group; MR, minimal response; PD, progressive disease; sCR, stringent complete response; SD, stable disease.

61 Results OS by cytogenetic riskOS by double-refractory state Time (days) Number of patients at risk Relapsed Refractory Survival (%) Time (days) 1.00 Survival (%) Number of patients at risk Relapsed Refractory Not double-refractory Double-refractory Standard risk High risk Adverse cytogenetics did not appear to influence risk of death as of last study follow- up. HR 1.05, 95%CI (0.49,2.26), P = A history of being double-refractory, however, approached a significant effect on survival time. HR 2.67, 95%CI (0.93,7.69), P = 0.068

62 IFM : Study design N = 50 RRMM Exposed to Len del 17p and/or t(4;14) Measurable disease ECOG 0–2 PNn > 1 x10 9 /L Plat ≥ 75 x10 9 /L Hb ≥ 8 g/dL CrCl ≥30 mL/min Pomalidomide 4 mg/day, po, days 1–21 (of 28 d cycle) Dexamethasone 40 mg, po, days 1, 8, 15, 22 Aspirin/LMWH once daily, continuously Until progression Safety analysis by DMC after 15 patients recruited End-points Primary: TTP Secondary:Safety, Response rate (CBR), DoR, OS, PFS, EFS, cytogenetic groups Median follow-up: 8.2 months n (%) Progression25 (69)Death other cause1 (3) Toxicity9 (25)Sponsor decision1 (3) At data cut-off, 36 patients (72%) had discontinued trial

63 O/NMedian95% CI ITT population33 / 502.9[2.7;5.0] 8-month TTP, %22 del17p12 / 22*7.3[2.7;14.7] 8-month TTP, %41 t(4;14)24 / 32*2.8[1.9;4.0] 8-month TTP, %12.4 IFM : Time To Progression (ITT)

64 O/NMedian95% CI ITT population26 / 5012[4.9;15.5] 8-month OS, %55 del17p12 / 22*12[2.4;-] 8-month OS, %58 t(4;14)16 / 32*9.2[4.6;-] 8-month OS, %50 IFM : Overall Survival

65 Shah JJ, et al. Blood. 2013;122:690. Phase I/II: Carfilzomib/Pomalidomide/LoDEX (Car-Pom-d) in R/R MM Carfilzomib* 20/27 mg/m 2 (D1-2, 8-9, 15-16) Pomalidomide* 4 mg (D1-21) Dexamethasone* 40 mg weekly (20 mg after cycle 4) Carfilzomib* 20/27 mg/m 2 (D1-2, 8-9, 15-16) Pomalidomide* 4 mg (D1-21) Dexamethasone* 40 mg weekly (20 mg after cycle 4) *Dosing based on MTD established in phase 1 Primary endpoint: ORR Secondary endpoints: DOR, TTP, PFS, time to next therapy, OS Study Population (N=79) Relapsed and/or refractory measurable MM Lenalidomide-refractory 28-day cycles (cycles 1-6) Carfilzomib D1-2, Pomalidomide unchanged Dexamethasone unchanged Carfilzomib D1-2, Pomalidomide unchanged Dexamethasone unchanged Maintenance (cycles 7+) Treatment continued until PD or unacceptable toxicity All patients received antiviral treatment and aspirin 81 mg or low molecular weight heparin

66 Car-POM-d in R/R MM: Efficacy Cytogenetic Risk (by mSMART) Response, % High (n = 18) Intermediate (n = 19) Standard (n = 38) All Pts (N = 79) ORR VGPR PR Median PFS: 9.7 mos; median DOR: 17.7 months; median OS not reached No significant difference in PFS or OS based on cytogenetics 80% of pts with del(17p) were alive at 12 mos; 58% were progression-free Shah JJ, et al. Blood. 2013;122:690.

67 Bortezomib Carflizomib Ixazomib Oprozomib Thalidomide Lenalidomide Pomalidomide Romidepsin Vorinostat Panobinostat Proteosome Inhibitors Immunomodulating Agents HDAC inhibitors

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69 Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma Niesvizky et al, Cancer Volume 117, Issue 2, pages , 22 SEP 2010 Volume 117, Issue 2,

70 Description RegimenN ORR (> PR), % HDAC Inhibitors Romidepsin + bortezomib + dex [4] 2560 Vorinostat + bortezomib [5] Bortezomib + panobinostat + dex [6] HDAC Inhibitors in RRMM

71 Vorinostat Bortezomib vs Placebo Bortezomib Dimopoulos et al, Lancet Oncol Oct;14(11): Vorinostat: Median PFS: 7·63 months (95% CI 6·87-8·40) Placebo: Median 6·83 months (5·67-7·73) (hazard ratio [HR] 0·77, 95% CI 0·64-0·94;p=0·0100).

72 PANORAMA 1: Phase III Trial of Panobinostat + Bortezomib + Dex Study Population (N=768) Relapse or relapsed/refractory MM Bortezomib-refractory excluded 1-3 prior lines of therapy Panobinostat Bortezomib Dexamethasone Placebo Bortezomib Dexamethasone Primary endpoint: PFS Stratification based on prior lines of therapy, prior bortezomib Richardson PG, et al. ASCO Abstract 8510.

73 PANORAMA 1: Primary Endpoint Met (PFS)

74 Bortezomib Carflizomib Ixazomib Oprozomib Thalidomide Lenalidomide Pomalidomide Melphalan Cyclophosphamide Bendamustin Romidepsin Vorinostat Panobinostat

75 Autotransplant for Refractory MM PFSOS N = 66 Median = 11 mo N = 66 Median = 19 mo SWOG Trial 8993 Vesole DH, et al. J Clin Oncol. 1999;17:

76 PBSCT in Relapsed MM Cook G et al,The Lancet Oncology, Volume 15, Issue 8, Pages , July 2014Volume 15, Issue 8, Pages , July 2014 Consolidation Induction PAD Weekly CTX 400 mg/m2 x 21 HD Mel TTP median HD Mel 19 months [95% CI 16—25] Cyclophosphamide 11 months [9—12]; hazard ratio 0·36 [95% CI 0·25—0·53]; p<0·0001).

77 A Phase 1 Study of Bendamustine and Melphalan Conditioning for Autologous Stem Cell Transplant with Multiple Myeloma.

78 Dose Levels for Bendamustine Dose LevelOn Day 1 Melphalan (100mg/m 2 ) On Day 2 Melphalan (100mg/m 2 ) 130 mg/m mg/m mg/m mg/m mg/m 2 60 mg/m mg/m mg/m 2

79 Bortezomib Carflizomib Ixazomib Oprozomib Thalidomide Lenalidomide Pomalidomide Filanesib Palbociclib Melphalan Cyclophosphamide Bendamustine Romidepsin Vorinostat Panobinostat Elotuzumab Daratumumab SAR650984

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81 The Team and Collaborators Tomer Mark MD Morton Coleman, MD Roger Pearse, MD Adriana Rossi, MD David Jayabalan Karen Pekle RNP Arthur Perry PA Susan Matthew, PhD Scott Ely, MD/MPH Selina Chen-Kiang, PhD Monica Guzman, PhD Giorgio Inghirami, MD Linda Tegnestam RN Kathleen Pogonowski RN Stanley Goldsmith MD Maureen Lane PhD Paul Christos Myelomacenter.org


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