new paradigms, new treatments in relapsed/refractory disease: an update kenneth c. anderson, m.d....
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New Paradigms, New Treatments in Relapsed/Refractory Disease: An Update
Kenneth C. Anderson, M.D.
Jerome Lipper Multiple Myeloma CenterDana-Farber Cancer Institute
Harvard Medical School
Conflict of Interest: Kenneth C. Anderson, M.D.
Consultancy: Celgene, Onyx, Sanofi Aventis, and Gilead
Scientific Founder: Acetylon, Oncopep
Integration of Novel Therapy
Into Myeloma Management Bortezomib, Lenalidomide, Thalidomide, Doxil, Carfilzomib, Pomalidamide
Target MM in the BM microenvironment to overcome conventional drug resistance in vitro and in vivo
Effective in relapsed/refractory, relapsed,induction, consolidation, and maintenance therapy
Eight FDA approvals and median survival prolonged from 3-4 to 6-7 years, with additional prolongation from maintenance
New approaches needed to treat and ultimately prevent relapse
Relapsed or Intolerant
There is a well defined and recognizedunmet need in multiple myeloma treatment
Adapted from: Durie BGM. Multiple Myeloma. International Myeloma Foundation. 2011/2012 edition.Jagannath S. Clin Lymphoma Myeloma. 2008;8 Suppl 4:S149-S156.
Unmet Need
Relapsed Frontline Treatment
Expectedsurvival (m)
20-50
Sensitivity totherapy
Sensitive
Treatment limitations/comorbidities
Peripheral neuropathy
(~15% at diagnosis)
14-16
Less Sensitive/Resistant
>80% incidence of peripheral neuropathyCompromised marrow
reserveCytopenia
6-10
Resistant
Intolerant to or ineligible for available
therapy
Elderly population ( risk for heart, lung, renal, liver dysfunction, diabetes)
Overview of Phase III Trials with Len and Bortezomib in Relapsed/Refractory MM
1. Weber DM, et al. N Engl J Med. 2007;357:2133-2142. 2. Dimopoulos M, et al. N Engl J Med. 2007;357:2123-2132. 3. Richardson PG, et al. Blood. 2007;110:3557-3560. 4. Orlowski RZ, et al. J Clin Oncol. 2007;25:3892-3901. 5. Weber D, et al. Blood. 2007;110:Abstract 412.
Regimen Trial ORR, %
CR or nCR, %
≥ VGPR, %
DOR, Mos
TTP or PFS, Mos
Median OS, Mos
Len + dex MM-009[1] 61 24 NE16 11
35[5]
Len + dex MM-010[2] 60 25 NE 17 11
Bortezomib APEX[3] 43 16 NE 86
30
VdoxMMY-3001[4] 44 13 27
109 NE
Efficacy and Toxicity by Bortezomibschedule
46.8 mg/m267.6 mg/m267.6Total planned dose
4%16%NAPN discontinuation
35%32%NAPFS @ 3 years
2%14%13%Grade 3-4
NA
44%
30%
VMP*(VISTA)
40 mg/m2
21%
23%
VMP once weekly N=190
Sensory PN
43%Any grade
41 mg/m2Total delivered dose
27%CR
VMP twice weekly N=63
**MateosMateos et al. J et al. J ClinClin OncolOncol 2010; 2010; PN: peripheral neuropathy
Palumbo et al. ASH 2010 abstr 620.
SC vs IV Bortezomib for Relapsed/Refractory Myeloma
EQUIVALENT EFFICACY
Peripheral Neuropathy Bortezomib IV
(N=74)
Bortezomib SC (N=148)
P-value*
Any PN event, % 53 38 0.04
Grade 2, % 41 24 0.01
Grade 3, % 16 6 0.03
Risk factors for PN, %
Grade 1 PN at baseline 28 23
Diabetes at baseline 11 13
Exposure to prior neurotoxic agents 85 86
*P-values are based on 2-sided Fisher’s exact test
Moreau et al, ASH 2010 abstr 312
• Lenalidomide induces caspase 8 mediated apoptosis of MM cells in BM in vitro and in vivo; Dex (caspase 9) enhances response
• Synergistic MM cell toxicity of lenalidomide (caspase 8) with Bortezomib (caspase 9>8) in vitro and in vivo (dual apoptotic signaling)
• Phase I-II trials show that majority (58%) of patients refractory to either agent alone respond to the combination
• Phase I-II trials show 100% response with 74% CR/VGPR and 52% CR/nCR when used as initial therapy, including molecular responses.
Bortezomib, Lenalidomide and Dex Therapy
Richardson et al. JCO 2009; 27:5713-19.Richardson et al. Blood 2010; 116:679-86.
Carfilzomib: A Novel Proteasome (Chymotryptic) Inhibitor
• Novel chemical class with highly selective
and irreversible proteasome binding
• Improved antitumor activity with
consecutive day dosing
• No neurotoxicity in animals
• Durable responses in relapsed and relapsed/ refractory MM w/o neuropathy
• Carfilzomib lenalidomide Dex versus lenalidomide Dex phase III trial for new drug approval
Demo et al. Cancer Res 2007; 67:6383 Kirk et al., Blood 2008, 112: 2765 Siegal et al. Blood 2012:120:2817.
HN
NH
O HN
O
O
NHO
NO O
O
Epoxyketone
Tetrapeptide
Benefit of Carfilzomib in Relapsed/Refractory MM:
Meaningful ORR, DOR and OS
Response Category Total N = 266, n (%)
1 (0.4)
VGPR 13 (4.9)
PR 47 (17.7)
MR CR
SD 81 (30.5)
PD 69 (25.9)
Not evaluable 21 (7.9)
ORR = 22.9% (95% CI: 18.0, 28.5)
Overall Survival Median OS = 15.4 months (95% CI: 12.5, 19.0)
CBR = 35.7% (95% CI: 30.0, 41.8)
Duration of response Median DOR = 7.8 months (95% CI: 5.6, 9.2)
CRd in Relapsed and Upfront MMWang et al ASCO 2011; Jakubowiak et al ASH 2011
• Response to CRd therapy was high, with an ORR of 78%
– 41% VGPR or better
• CRd well-tolerated with durable responses
• ASPIRE phase 3 open-label, international, multicenter trial comparing CRd to Rd in R/R MM fully enrolled.
• Remarkable extent and frequency of response to CRd upfront (100% ORR, 80% CR,nCR after 12 cycles)
Jakubowiak A. et al., Blood, 2012; 120: 1801-8.
Carfilzomib in Relapsed/Refractory MM
Study Ph BTZ status nMedian prior tx
linesCFZ dose Mode of
admin ORR
PX-171-003-A11
II Relapsed and refractory
266 5 20/27 mg/m2 2-10 min IV infusion
24%
PX-171-0072
I/II Relapsed and/or
refractory
20 4.5 20/56 mg/m2 30-min IV infusion
60%
1. Siegel et al. Blood. 2012;120(14):2817-2825 2. Papadopoulos KP, et al. Blood. 2011;118(21):Abstract and poster 2930.
Phase II Study of Infusional Carfilzomib in Patients with Relapsed or Refractory MM
• CFZ dose of 20/56 mg/m2 administered as a 30-minute IV infusion resulted in high response rates in our BTZ treated/refractory population.
• Response rates were comparable to those seen in PX-171-0071
• CFZ dose of 20/56 mg/m2 was associated with more frequent cardiac and pulmonary toxicities, particularly HTN and pulmonary edema/CHF.
– Possible contribution from “supportive” measures?
• CFZ dose of 20/56 mg/m2 continues to be explored in ongoing Phase II/III studies. Lendvai et al, ASH 2012 Abstr 947
Pomalidomide in Myeloma
MM cells
Bone Marrow Stromal Cells
Dendritic
Cells
IL-6
TNFIL-1A
IL-2
IFN
CD8+ T Cells
C
E
Bone Marrow Vessels
ICAM-1
VEGFbFGF
D
B
NK CellsNK-T Cells
Hideshima et al. Blood 96: 2943, 2000Davies et al. Blood 98: 210, 2001Gupta et al. Leukemia 15: 1950, 2001
Mitsiades et al. Blood 99: 4525, 2002Lentzsch et al Cancer Res 62: 2300, 2002 LeBlanc R et al. Blood 103: 1787, 2004Hayashi T et al. Brit J Hematol 128: 192, 2005
PKCNFAT
PI3K
IL-2
CD28
Pomalidomide With Low-Dose Dexamethasone Relapsed and Refractory Multiple Myeloma
• POM was effective in heavily pretreated patients who had already received LEN and bortezomib and who progressed on their last line of therapy
• The combination of POM with LoDEX improves the ORR due to synergy between immunomodulatory agents and glucocorticoids
– POM + LoDEX, 34%; POM alone, 15%
• Response was durable with POM regardless of the addition of LoDEX
– POM + LoDEX, 8.3 months ; POM alone, 8.8 months
• POM is generally well tolerated, with low rates of discontinuations due to AEs
• Age had no impact on ORR, DoR, or safety
Jagannath S, et al. ASH 2012 abstract 450.
Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Relapsed Myeloma (345 patients)
• Pom/Dex has high response rates even in heavily pretreated relapsed myeloma
• Pom/Dex is well tolerated
• Toxicity and efficacy are similar between the 2mg and 4mg dose levels
• The strongest predictors of response include the number and type of prior regimens.
• The strongest predictors of TTP and survival include the number and type of prior regimens, LDH, and B2M.
Lacy et al. ASH 2013 Abstr 201.
A Phase III Clinical Trial of Pomalidomide with Low-dose Dex vs. High-dose Dex in
Relapsed/Refractory MM• POM + LoDEX significantly improved PFS and OS
– Median PFS: 3.6 vs 1.8 months
• HR = 0.45; P < .001
– Median OS: not reached vs 7.8 months
• HR = 0.53; P < .001
• Equal benefit in pts refractory to both LEN and BORT
• POM + LoDEX was generally well tolerated
• POM + LoDEX should be considered as a new treatment option for these pts
Dimopoulos et al. ASH 2013 LBA6
MM-005: A Phase 1 Trial of Pomalidomide, Bortezomib, and Low-dose Dexamethasone in
Relapsed or Relapsed/Refractory MM
• POM + BORT + LoDEX (PVD) well tolerated– cohort 5 as the MTD/MPD
• POM 4 mg; BORT 1.3 mg/m2; DEX 10/20 mg
• Responses in RR MM across all cohorts– ORR: 73%, VGPR: 27%, SD: 27% – Responses were rapid; majority are ongoing– Efficacy even with adverse cytogenetics
• Phase III Trial Pom Bort Dex vs Bort Dex for full approval
Richardson et al. ASH 2013 Abstr 727.
Carfilzomib Pomalidomide Dexamethasone (Car-Pom-d) in Relapsed/Refractory MM
• MTD was Carfilzomib 20/27 mg/m2, Pomalidomide 4 mg, and dexamethasone 40 mg
• There are limited G 3 and 4 non hematologic toxicities; the regimen was tolerated well with no unexpected toxicity
• The combination of Car-Pom–d is highly active in this heavily pretreated, refractory patient population
• The combination has encouraging preserved response rate and survival independent of FISH/cytogenetic risk status
≥ VGPR 13% ≥ ORR 50% ≥ CBR 67% PFS (median) 7.4 months OS 90% @ 1 year
Shah et al. ASH 2012 Abstr 74.
1. Development of immune therapies
2. Development of novel agents targeting the MM cell in the BM microenvironment
3. Development of rationally-based combination therapies
4. Utilization of genomics for improved classification and personalized therapy
Myeloma will be a chronic illness, with sustained CR in a significant fraction of patients.
Current and Future Directions
Antibody-dependentCellular cytotoxicity
(ADCC)
ADCC
Effector cells:
MM
FcR
Complement-dependentCytotoxicity (CDC)
CDC
MM
C1q
C1q
Apoptosis/growth arrest
via targetingsignaling pathways
MM
Lucatumumab or Dacetuzumab (CD40)Elotuzumab (CS1)Daratumumab (CD38)XmAb 5592 (HM1.24)
huN901-DM1 (CD56)nBT062-maytansinoid
(CD138)1339 (IL-6)BHQ880 (DKK1)RAP-011 (activin A)Daratumumab (CD38)
Daratumumab (CD38)
MAb-Based Therapeutic Targeting of Myeloma
Tai & Anderson Bone Marrow Research 2011
Phase 2 Elotuzumab Lenalidomide Low-dose Dex in Relapsed/ Refractory MM
• Elotuzumab plus lenalidomide and low-dose dexamethasone has a high ORR in relapsed and relapsed/refractory MM
– 82% for all pts (91% in pts who had received only 1 prior therapy)
– 92% for pts treated with elotuzumab 10 mg/kg
Median PFS was 33 mos for patients receiving elotuzumab 10 mg/kg
• The combination was generally well tolerated
– Most common Grade 3/4 treatment-emergent AEs were neutropenia (16%), thrombocytopenia (16%), and lymphopenia (16%)
– Premedication regimen decreased incidence and mitigated severity of infusion reactions*
Richardson et al. ASH 2012, Lonial et al. ASCO 2013
PHASE I/II STUDY OF DARATUMUMAB CD38 MONOCLONAL ANTIBODY IN
RELAPSED/REFRACTORY MM • Favorable safety profile as monotherapy
• In 15 of 32 (47%) showed benefit
– 4 patients achieving PR (13%)– 6 patients achieving MR (19%)– 5 patients achieving SD (16%)
• At doses 4mg/kg and above, 8 of the 12 patients had at least MR (66%)
• To be combined with lenalidomide dexamethasone
Plesner et al. ASH 2012 Abstr 73.
Phase I Trial of Vaccination with DC/MM Fusions in Relapsed Refractory MM
• Well tolerated, no autoimmunity
• Induced tumor reactive lymphocytes in a majority of patients
• Induced humoral responses to novel antigens (SEREX analysis)
• Disease stabilization in 70% of patients
Rosenblatt et al. Blood 2011; 117:393-402
• DC/MM fusions induce anti-MM immunity in vitro and inhibit MM cell growth in vivo in xenograft models
• Vasir et al. Brit J Hematol 2005; 129: 687-700
Background: MM/DC Vaccination following Autologous PBSCT for Myeloma
29%
54%
38%
25%
33% 13%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
100 Day Post-Transplant Post 100 Day (Best Response)
% P
artic
ipan
ts
CR/nCR VGPR PR
Rosenblatt et al., CCR 2013
PD-L1 Plays an Important Role in Dampening the Anti-tumor Immune Response
Stromal PD-L1 modulation of T cells
Immune cell modulation of T cells
PD-L1/PD-1-mediated Inhibition of
tumor cell killing
IFNg-mediated
up-regulation of tumor PD-
L1
Priming and Activation of T cells
PD-L2 mediated inhibition of TH-2 T cells
receptor
Chen DS, Irving BA, Hodi FS. Clin Cancer Res. 2012;18:6580.
PD-L1 expression in the tumor microenvironment can inhibit anti-tumor T cell activity:
1. PD-L1 expression by tumor infiltrating immune cells
2. PD-L1 expression by cancer cells
cancer cell
PD-L1
lymphocyte
Presence of intratumoral T-cells may lead to adaptive immune resistance
Combination Immunotherapy Posttransplant
• Anti PD-1 Ab administration in the early post-autologous transplant period is well tolerated
• Anti-PD1 results in the expansion of tumor reactive lymphocytes in the post-transplant period that persist at 6 months
• This provides a promising platform for combination with a tumor vaccine
• We have inititated enrollment into cohort 2, in which patients receive an autologous DC/myeloma fusion vaccine 1 week prior to each dose of Anti-PD-1Ab
Avigan et al.
20S20S
19S
19S
a b5, 5i1, 1i2, 2i
ATPases/Cdc48
PotentialTherapeutic Targets
26S PROTEASOME
ATP ADP
UB enzymes E1, E2 andE3-UB-Ligases
UbUb
Ub
Poly-ubiquitinated proteins (proteasome substrates)
Free for re-cycling
Six Proteaseactivities
Degraded proteinUb
Immunoproteasome
Proteasome: Present and Future Therapies
DeubiquitylatingEnzymes (DUBs)
Bortezomib, Carfilzomib, CEP-18770ONYX-0912MLN 2238
NPI-0052: 5, 1, 2
5
PR-924P5091 target USP-7
P5091 Specifically Target USP-7 and does not Alter Proteasome Activity
P5091 (µM) 2.5 5 7.5 10 12.5 Velcade (nM) 1 3 5 7 9
USP-7 Knockout Proteasome Activity Assay
Chauhan et al. Cancer Cell 2012;22: 345-58
P5091 Overcomes Bortezomib-Resistancein MM Cells
Chauhan et al. Cancer Cell 2012; 22: 345-58
MLN2238/9708 Decreases Cell Viability in MM Cells and Overcomes Bortezomib-
Resistance
24h 48h
Chauhan et al., Clin Cancer Res, 2011; 17: 5311-21.
Weekly MLN9708 in Relapsed/Refractory Multiple Myeloma: Phase I Study
• Single-agent oral MLN9708 MTD 2.97 mg/m2 on a weekly (days 1, 8, and 15 every 28 days) schedule
• Oral MLN9708 generally well tolerated– hematologic and gastrointestinal events generally
manageable, low rate of discontinuations – Infrequent PN, only 1 grade 3 PN
• Pharmacokinetic profile supports weekly oral dosing
• Relapsed and/or refractory MM patients (median 4 prior lines of therapy)– ORR (≥PR) of 18%, plus 2% MR and 30% SD, including
relapse post BortezomibKumar ASCO 2013
MLN9708 in Relapsed and/or Refractory MM: Expansion Cohorts of a Phase 1 Dose-
Escalation study• 46 pts evaluable for response
– 21 in dose-escalation cohorts
– 30 in expansion cohorts (including 6 from dose-escalation cohorts)
• 6 pts have achieved ≥PR
– 1 CR, confirmed by bone marrow (PI-naïve expansion cohort)
– 5 PRs (1 each at 1.2 and 2.23 mg/m2 in dose-escalation cohorts; 1 in RRMM and 2 in bortezomib-relapsed expansion cohorts)
• 1 pt achieved MR (bortezomib-relapsed expansion cohort; 40% M-protein reduction)
• All 7 pts remain in response, with duration of disease control of up to 15.9 months
• 28 pts have achieved SD
– 14 in dose-escalation cohorts
– 9, 5, and 2 in RRMM, bortezomib-relapsed, and PI-naïve expansion cohorts
– Durable, with disease stabilization for up to 12.9 months
Richardson et al. ASH 2011
• Phase I clinical trials ongoing
In Vitro Anti-MM Activity of Oral Chymotryptic Inhibitor ONX 0912 (Opromazib)
Myeloma Cell Lines Patient Tumor Cells
Chauhan et al. Blood. 2010;116:490614
Marizomib: A Non-Peptide Proteasome Inhibitor Induces Rapid, Broad and Prolonged Inhibition
Chauhan et al., Cancer Cell 2005; 8: 407-19
• Exhibits high levels of proteasome inhibition
without toxicities associated with bortezomib
• Active in bortezomib and IMiD resistant myeloma preclinically
Marizomib (NPI-0052)
HN
O
O
O
CH3
OH
Cl
H
H
H
Responses to Marizomib +/- Dexamethasone in Evaluable Pts at Full Dose [ >0.4 mg/m2 ]* Twice Weekly (n=21**)
All PtsEBMT ≥ SD 11/20 55%MR + PR 3/20 15%
Uniform Criteria ≥ SD 12/21 57%PR + VGPR 4/21 19%
Pts Exposed to Bortezomib EBMT ≥ SD 11/19 58%MR + PR 3/19 16%
Uniform Criteria ≥ SD 11/19 58%PR + VGPR 3/19 16%
*As of 05 Dec 11
• Response criteria defined with baseline SPEP ≥ 0.5 g/dL or UPEP ≥ 200 mg/24h with at least 2 assessments after treatment Day 1 for EBMT ; also by free lite for UC**.
• Refractory defined as having PD during or within 60 days of last regimen.
Pts Refractory to BortezomibEBMT ≥ SD 8/12 67%MR + PR 2/12 17%
Uniform Criteria ≥ SD 8/12 67%PR + VGPR 2/12 17%
Pts Refractory to LenalidomideEBMT ≥ SD 8/13 62%MR + PR 3/13 23%
Uniform Criteria ≥ SD 9/14 64%PR + VGPR 4/14 29%
Median Duration of Response (all Pts) = 133 days (~ 5 mos)
Richardson et al. ASH 2011
MM
Functional Sequelae of Btk Inhibition by PCI-32765 in the MM BM milieu
Osteoclast precursors Osteoclast
M-CSF, IL-6, MCP-1
PCI32765
IL-6SDF-1MIP-1MIP-1M-CSFMCP-1
PCI-32765
M-CSF
TRAP5bSDF-1IL-8Activin AAPRILMIP-1MIP-1TGF1RANTESBAFF
Stromal cellsfms
RANK Boneresorption
Tumor microenvironment
Adhesion MigrationHoming
PCI32765
MM Stem Cell
Btk activation by IL-6, SDF-1
Colony formation
MIP-1, MIP-1, IL-8, TGF1RANTES, BAFF, TRAF2, CXCR4, LAT, PLC2, MYD88, NFATc1
Tai et al. Blood2012; 120: 1877-87.
Delmore JE., Issa GC, et al. Cell 2011; 146:904.
BET Bromodomain Inhibition Suppresses c-myc Expression and Function and Triggers Anti-MM
Activity
Additional Targeted Therapies in Development
KSP inhibitors (Array 520)
AKT inhibitor (GSK agent)
Nuclear transport inhibitors (KPT)
CDK inhibitors
Protein
protein aggregates(toxic)
UbUb
UbUb
26S proteasome
UbUb
Ub Ub
Ub
Aggresome
Panibinostat,Vorinostat, ACY1215
dynein
UbUb
dynein
MicrotubuleAutophagy
Bortezomib, Carfilzomib, NPI0052, MLN9708, ONX 0912
Ub Ub
Ub
Lysosome
HDAC6
HDAC6
HDAC6
Ub
Ub
Development of Rationally-based Combination Therapies (HDAC and Proteasome Inhibitors)
Hideshima et al. Clin Cancer Res. 2005;11:8530.Catley et al. Blood. 2006;108:3441-9.
VANTAGE 088: An International, Multicenter, Randomized, Double-Blind Study of Vorinostat
or Placebo with Bortezomib in Relapsed MM
• The combination of vorinostat + bortezomib is active in patients with relapsed and refractory MM– Significant improvement in response rate– ORR 54% vs 41% (P<0.0001); CBR 71% vs 53% (P<0.0001)
• PFS and TTP were prolonged in the combination arm compared with bortezomib alonePFS hazard ratio reduction of 23% (P=0.01); 7.63 months (6.9–8.4)
versus 6.83 months (5.7–7.7)
• Diarrhea, fatigue, and thrombocytopenia limited tolerability
Dimopoulos et al. ASH 2011, Lancet Oncology, in press
Bench to Bedside Translation of HDAC 6 Selective Inhibitor ACY 1215
• Orally bioavailable, highly potent, selective • inhibitor of HDAC 6 synthesized in fall 2009
• Synergistic MM cytotoxicity with Bortezomib • in vitro and in vivo
• Favorable PK/PD, toxicity profile
•Phase Ia/Ib/II clinical trials of ACY1215, alone and with Bortezomib and with lenalidomide/dexamethasone, ongoing; trials with pomalidomide and carfilzomib this year.
Santo et al. Blood 2012;119:2579-89
Mutations in Myeloma19 Patients Each With
Newly Diagnosed and Relapsed MM
• Protein homeostasis: 42% including FAM46C, RPL10, RPS6KA1, EIF3B, XBP1, LRRK2
• NF-kB signaling: 10 point mutations, 4 additional structural re-arrangements affecting codingConfers bortezomib sensitivity
• Histone methylating enzymes: WHSC1, UTX, MLL
• BRAF: 4% activating : Single patient MM response Andrulis et al Cancer Discovery 2013; 3: 862-9.
• PSMB5 b5 proteasome subunit mutation confers proteasome inhibitor resistance in laboratory, not identified in clinic
Lichter et al Blood 2012: 120: 4513-16.
Chapman et al. Nature 2011; 471: 467-72.
EARLY
LATE
PRAMEF12
NRAS
USH2A
ASXL2
NCKAP5PLS1
ACOT12
PCDHB6
CDKAL1
COL9A1
TIAM2
LRRC69
TRPM3
0
0.2
0.4
0.6
0.8
1
1.2
PD4301
%MutLate%MutEarly
Early mutationnot in late sample
New mutations in late sample
Early Tumor Late Tumor
Whole Genome Sequencing Identifies Acquisition of New Changes in MM: 71 Patient Study
(Munshi et al, ASH 2011 Abstract 276)
Early Tumor Late Tumor
1. Lenalidomide dexamethasone, bortezomib, and pegylated doxorubicin are approved regimens for relapsed MM.
2. Pomalidomide/dex and carfilzomib are newly FDA approved options.
3. There are many promising protocols of novel immune and targeted agents which show promise, alone and in combination.
4. Genomic analyses are both defining the basis for evolution underlying relapse and identifying new targets.
Relapsed Refractory Myeloma
United Nations Against Myeloma:
Bench to Bedside Research TeamKenneth AndersonNikhil MunshiPaul RichardsonRobert SchlossmanIrene GhobrialSteven TreonJacob LaubachDeborah DossKathleen ColsonMary McKenneyKim NoonanTina FlahertyKathleen Finn Muriel GannonStacey ChumaJanet KunsmanDiane WarrenCarolyn RevtaAndrea FreemanAlexis FieldsAndrea KolligianJohn FeatherFarzana MasoodNora LoughneyHeather GoddardTiffany PoonNicole StavitzskiRanjit BanwaitShawna CormanHeather GoddardMeghan Marie LeahyCaitlin O’GallagherChristina TripsasKarin AndersonShannon VieraKatherine RedmanAmber WalshSamir AminWanling XieParantu ShahHolly BartelLisa PopitzJeffrey Sorrell
Teru HideshimaConstantine MitsiadesDharminder ChauhanNoopur RajeYu-Tzu TaiRuben CarrascoJames BradnerGullu GorgunJooeun BaeFrancesca CottiniMichele CeaAntonia CagnettaTeresa CalimeriEdie WellerAjita SinghZe TianDiana CirsteaYiguo HuNaoya MimuraJiro MinamiSun-Yung KongWeihua SongDouglas McMillinCatriona HayesSteffen KlippelJana JakubikovaPanisinee LawasutNiels van de DonkEugen DhimoleaJake DelmoreHannah JacobsMasood ShammasMariateresa FulcinitiJianhong LinJagannath PalSamantha PozziLoredana SantoClaire FabreAnuj MahindraRao PrabhalaJake DelmorePuru NanjappaMichael SellitoAvani Vaishnav
USA
UK
India
Italy
Japan
Canada
Germany
China
Greece
Taiwan
Australia
IrelandIsrael
Turkey
Austria
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