Challenging Cases in Multiple Myeloma

1

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2
Challenging Cases in Multiple MyelomaOncologist
and Nurse Investigators Consult on Actual
Patients from the Practices of the Invited
FacultySaturday, May 3, 2014600 AM 730 AM
Faculty
Charise L Gleason, MSN, ANP-C, AOCNP Tiffany
Richards, MS, ANP-BC, AOCNP
P Leif Bergsagel, MD Jeffrey L Wolf, MD
ModeratorNeil Love, MD
3
Oncology 6-Part Case Series Key Themes

• Mechanisms of action of novel agents and tissue
  assays to predict response
• Side effects and toxicities of novel agents dose
  adjustments
• Assessment and management of adherence
• Specific goals of therapy and likely outcomes
  sequencing of agents in advanced disease
• Local and systemic complications of cancer
  Fatigue, pain, CNS involvement
• Care of older, frail patients and those with
  comorbidities

4
Oncology 6-Part Case Series Key Themes

• Clinical trials as a means to access new
  treatments earlier
• Management of anxiety and depression
• Key determinants of patient satisfaction What do
  people with cancer want and need?
• Quality, value and cost Investing resources
  optimally
• End-of-life care and planning
• Impact of the cancer experience on family and
  loved ones, including minor children
• Impact of the oncology experience on oncology
  health professionals

5
Agenda

• Two Younger Patients Who Were Candidates for
  ASCT
• 46 yo woman who completed RVDD and has been in
  remission for 5 years while on maintenance
  lenalidomide (Ms Gleason)
• 66 yo man who received RVD followed by ASCT and
  lenalidomide/ixazomib maintenance (Ms Richards)
• An Elderly Patient with Multiple Myeloma
• 85 yo non-English-speaking Vietnamese man who is
  receiving carfilzomib/dexamethasone for relapsed
  disease (Ms Richards)

6
Agenda

• Two Patients with Relapsed Multiple Myeloma
• 74 yo man with relapsed multiple myeloma and
  early signs of dementia (Ms Gleason)
• 64 yo man with relapsed mutliple myeloma who is
  experiencing corticosteroid-related symptoms (Ms
  Richards)
• A Patient with Plasma Cell Leukemia and Adverse
  Cytogenetics
• 54 yo mother of a teenage daughter who is now in
  complete remission (Ms Gleason)

7
Two Younger Patients Who Were Candidates for ASCT

• 46 yo woman who completed RVDD and has been in
  remission for 5 years while on maintenance
  lenalidomide (Ms Gleason)
• 66 yo man who received RVD followed by ASCT and
  lenalidomide/ixazomib maintenance (Ms Richards)

8
Case 1 (from the practice of Ms Gleason)

• A 46-year-old woman was initially diagnosed with
  standard-risk MM in 2008, shortly after the birth
  of her second child
• She enrolled on a clinical trial of RVDD
  (lenalidomide/bortezomib/dexamethasone/doxorubicin
  ) x 8 cycles
• After cycle 4, stem cells were collected for
  future ASCT
• The patient was started on lenalidomide
  maintenance, which she has now received for
  almost 5 years
• She currently lives a normal lifestyle, working
  out at the gym regularly and taking care of her 2
  young children
• She has maintained a daily journal of her
  experience since diagnosis

9
Key Education Points for Patients with Newly
Diagnosed Multiple Myeloma
Transplant-Eligible
Transplant-Ineligible
Induction therapy
Induction therapy
Stem cell transplant
Maintenance therapy
Maintenance therapy
Relapsed disease
Relapsed disease
10
Potential curability of MM correlation between
depth of response and long-term outcome
Discussion Point
11
Getting to Minimal Residual Disease (MRD)
11012
Newly diagnosed
S.S. Patient
Disease burden
CR
1108
Stringent CR
1104
Molecular/Flow CR
?Cure?
0.0
12
Discussion Point

• Role of common genetic abnormalities in patient
  risk assessment and therapeutic decision-making

13
mSMART Mayo Stratification for Myeloma and
Risk-Adapted Therapy
Standard-Risk 60
High-Risk 20
Intermediate-Risk 20

• FISH
• Del 17p
• t(1416)
• t(1420)
• GEP
• High-risk signature

• All others including
• Hyperdiploidy
• t(1114)
• t(614)

• FISH
• t(414)
• Cytogenetic deletion 13 or hypodiploidy
• PCLI 3

3 years
4-5 years
8-10 years
Mikhael JR et al. Mayo Clin Proc
201388(4)360-76.
14
Discussion Point

• Rationale for the use of 3-drug combinations
  (versus 2) in the induction setting

15
Preferred Induction Regimens Transplantation
Eligible

• RD/Rd Lenalidomide/dexamethasone
• VD Bortezomib/dexamethasone
• RVD Bortezomib/lenalidomide/dexamethasone
• VTD Bortezomib/thalidomide/dexamethasone
• CyBorD Bortezomib/cyclophosphamide/dexamethasone
• PAD Bortezomib/doxorubicin/dexamethasone

NCCN. Clinical practice guidelines in oncology
multiple myeloma. v.2.2014.
16
An otherwise healthy 60-year-old patient presents
with fatigue. Workup reveals Hb 9.0 g/dL, normal
renal function, an M-spike with an IgG lambda
component of 4.9 g/dL and bone marrow consistent
with MM (ISS Stage II). Conventional
cytogenetics, FISH and skeletal survey are
normal. Which induction treatment would you most
likely recommend for this patient?
of respondents
Research To Practice Patterns of Care Study 2014
(N 101 practicing oncologists)
17
Phase III Noninferiority Trial of Subcutaneous
versus Intravenous Bortezomib
SubQ Bortezomib (n 148)
N 222 Relapsed MM 1-3 prior lines of therapy
21
R
Intravenous Bortezomib (n 74)
Best response (up to 10 cycles) 52 vs
52 Median PFS 9.3 vs 8.4 mo 1-yr OS 76 vs 78
Moreau P et al. Lancet Oncol 201112(5)431-40. Ar
nulf B et al. Haematologica 201297(12)1925-8.
18
When administering bortezomib for the following
situations, which route of administration and
schedule do you generally use?
INDUCTION THERAPY
of respondents
Research To Practice Patterns of Care Study 2014
(N 101 practicing oncologists)
19
SC Injection Site Rotation

• Within the same cycle
• Injections at the same site should be avoided
• Alternate between
• Right and left abdomen
• Upper and lower quadrantor between
• Right and left thigh
• Proximal and distal sites

Moreau P et al. Proc ASH 2010Abstract 312.
20
Subcutaneous (SC) Administration of Bortezomib
Local Side Effects of Injections

• In a Phase III noninferiority trial of SC versus
  IV bortezomib
• 1 SC injection site reaction 6 pts
• Most common reaction redness (57 pts)
• Injection site reactions 100 resolved in median
  of 6 days

Moreau P et al. Lancet Oncol 201112(5)431-40. Mo
reau P et al. Proc ASH 2010Abstract 312.

21
Discussion Point

• Preventing herpes zoster reactivation in patients
  who are receiving bortezomib

22
Thromboprophylaxis in patients receiving IMiDs
other side effects assessment of adherence to
oral medications
Discussion Point
23
Prophylaxis for Thromboembolism

• Aspirin
• None or one patient- or myeloma-related risk
  factor
• LMWH or Full-Dose Warfarin (INR 2-3)
• 2 patient- or myeloma-related risk factors
• All patients, independent of other risk factors,
  receiving
• High-dose dexamethasone
• Doxorubicin
• Multiagent chemotherapy

Palumbo A et al. Leukemia 200822(2)414-23.
24
Post-transplant consolidation and maintenance
therapy impact of cytogenetic profile
Discussion Point
25
N Engl J Med 20123661782-91.
N Engl J Med 20123661770-81.
26
Post-Transplant Maintenance Lenalidomide
Study Details n Treatment Outcome Outcome
IFM 2005-021 (Median follow-up 67 mo) 307 307 Lenalidomide Placebo PFS 46 mo 24 mo Median OS 82 mo 81 mo
CALGB-1001042 (Median follow-up 34 mo) 231 229 Lenalidomide Placebo TTP 46 mo 27 mo Median OS Not reached 73 mo
1 Attal M et al. Proc ASH 2013Abstract 406. 2
McCarthy PL et al. N Engl J Med 20123661770-81.
27
In general, when administering lenalidomide
maintenance therapy for a younger (60-year-old)
otherwise healthy patient with MM who responded
to induction therapy and ASCT, what is your usual
preferred starting dose?
of respondents
Research To Practice Patterns of Care Study 2014
(N 101 practicing oncologists)
28
Risk of second cancers in patients receiving
lenalidomide
Discussion Point
29
IFM 2005-02 Second Primary Cancers (SPMs)
Type of lesion Lenalidomide (n 306) Placebo (n 302)
Hematologic cancer 13 (4) 5 (2)
Solid tumors 10 (3) 4 (1)
Nonmelanoma skin cancer 5 (2) 3 (1)
Total 26 (8) 11 (4)
The incidence of second primary cancers (p
0.002) - Lenalidomide 3.1 SPMs per 100
patient-years - Placebo 1.2 SPMs per 100
patient-years
Attal M et al. N Eng J Med 2012366(19)1782-91.
30
CALGB-100104 Disease Progression and Second
Primary Cancers
Outcome Lenalidomide Placebo
3-year PFS 66 39
Second primary cancers Lenalidomide Placebo
Hematologic 8 (3.5) 1 (0.4)
Solid tumors 10 (4.3) 5 (2.2)
At a median follow-up of 34 months, a total of 92
of the 231 patients in the lenalidomide group
(40) as compared to 133 of the 229 patients in
the placebo group (58) had progressive disease,
had died or had received a diagnosis of a second
primary cancer (p lt 0.001).
McCarthy PL et al. N Engl J Med
2012366(19)1770-81.
31
CALGB-100104 Death
At a median follow-up of 34 months, a total of 35
patients who received lenalidomide (15) and 53
patients who received placebo (23) had died
(2-sided p 0.03).
McCarthy PL et al. N Engl J Med
2012366(19)1770-81.
32
Case 2 (from the practice of Ms Richards)

• A 66-year-old man presented with anemia and was
  found to have standard-risk, ISS Stage III
  multiple myeloma (MM)
• He received lenalidomide/bortezomib/dexamethasone
  (RVD) x 4 cycles followed by ASCT, after which he
  was enrolled on a nonrandomized Phase II clinical
  trial of maintenance therapy with ixazomib
  (MLN9708) and lenalidomide
• The patient is currently in complete remission
  and would like to travel this spring for a
  month-long visit to his home in Palestine

33
Patient Serum Paraprotein Levels After RVD and
Transplant
2.16
Bortezomib/Lenalidomide/Dexamethasone
1.94
1.73
1.51
1.3
1.08
g/dL
.86
Transplant
.65
.43
.22
2/6/2014
3/9/2013
12/26/2013
3/19/2014
4/20/2013
6/1/2013
7/12/2013
8/23/2013
10/4/2013
11/14/2013
Date
34
Discussion Point

• Novel proteasome inhibitors in the management of
  MM

35
Cellular Impact of Proteasome Inhibition in
Nonclinical Studies1-4
1. Proteasomes are enzyme complexes that degrade
intracellular proteins in a regulated manner in
all cells, both healthy and cancerous 2. Cancer
cells depend upon proteins regulated by the
proteasome for proliferation, metastasis and
survival 3. Inhibition of the proteasome by
bortezomib prevents the degradation of
intracellular proteins, affecting multiple
signaling cascades within cells 4. The disruption
of signaling cascades in cancer cells can lead to
cancer cell death and inhibit tumor growth
1 Invest New Drugs 200018109-21. 2 Physiol Rev
200282373-428. 3 Sci Am 200128463-73. 4 Cell
199892367-84.
36
Available data on carfilzomib as part of
up-front induction therapy and in the relapsed
setting
Discussion Point
37
Phase II Study of Carfilzomib (CFZ) Monotherapy
in Relapsed/Refractory MM
N 266 Relapsed/refractory MM 2 regimens for
relapsed MM Refractory to most recent Tx
including bortezomib
Intravenous CFZ 20 mg/m2 twice wkly for 3 of 4
wks in cycle 1, then 27 mg/m2 for 12 cycles

• ORR
• All patients 23.7
• Patients with adverse cytogenetics (n 71) 29.6

Siegel DS et al. Blood 2012120(14)2817-25.
38
Possible Side Effects Associated with Carfilzomib

• Grade 3 adverse events are mainly hematologic
• Low rates of neutropenia
• Nonhematologic adverse events include
• Fatigue
• Nausea
• Dyspnea
• Infrequent peripheral neuropathy

Siegel DS et al. Blood 2012120(14)2817-25.
39
Phase I/II Study of Front-Line Carfilzomib (CFZ)
in Combination with Lenalidomide and Dexamethasone
Continued lenalidomide recommended (off protocol)
CRd Induction
CRd Maintenance
Transplant-eligible and ineligible patients
LEN Cycles 25
CRd Cycles 924
CRd Cycles 14
CRd Cycles 58
Transplant-eligible with PR may undergo ASCT

• After a median of 12 cycles
• nCR 62 sCR 42
• Grade 3 PN 0

Jakubowiak AJ et al. Blood 2012120(9)1801-9.
40
Phase III ECOG-E1A11 Trial
Trial Identifier NCT01863550 Estimated
enrollment 756 (open)
Carfilzomib lenalidomide low-dose
dexamethasone ? lenalidomide maintenance
Eligibility
Newly diagnosed standard-risk MM ECOG PS 0-2 No history of Grade 2 peripheral neuropathy
R
Bortezomib lenalidomide low-dose
dexamethasone ? lenalidomide maintenance
Maintenance may be limited to 24 courses or
indefinite

• Primary endpoint Overall survival for
  maintenance-therapy analysis
• Select secondary endpoints Progression-free
  survival, overall response rate, duration of
  response

www.clinicaltrials.gov, Accessed April 2014.
41
Discussion Point

• Incidence and management of carfilzomib-associated
  peripheral neuropathy

42
Incidence and Management of CFZ-Associated
Peripheral Neuropathy

• CFZ is associated mostly with Grade 1/2 PN
• All-grade CFZ-related PN was observed in 8.3 of
  patients
• No Grade 4 PN observed on study
• PN can be resolved with drug interruption

Siegel DS et al. Blood 2012120(14)2817-25.
43
Discussion Point

• Other rare but important toxicities with
  carfilzomib pulmonary hypertension and cardiac
  events

44
Oral proteasome inhibitors in development
(ixazomib, oprozomib)
Discussion Point
45
Key Features of Ixazomib and Bortezomib
Compound Chemical Binding Adm Status
Bortezomib Boronate Reversible IV/SC FDA approved
Ixazomib Boronate Reversible Oral/IV Phase I-III
Bortezomib
Ixazomib
Adapted from Fostier K et al. OncoTargets and
Therapy 20125237-44.
46
Phase I/II Study of Weekly Ixazomib Combined with
Lenalidomide and Dexamethasone in Previously
Untreated MM
Induction up to 12 x 28-day treatment cycles
Maintenance
1
8
15
22
28
MLN9708 maintenance Days 1, 8, 15 28-day cycles
MLN9708
MLN9708
MLN9708
Dex 40 mg
Dex 40 mg
Dex 40 mg
Dex 40 mg
Lenalidomide 25 mg, days 121

• ORR 92 VGPR 55
• Grade 3 PN 3

Kumar SK et al. Proc ASH 2012Abstract 332.
47
Ongoing Phase I/II Trials of Oprozomib in Newly
Diagnosed MM
Trial Identifier Clinical Setting Treatment Arms Estimated Primary Completion Date
NCT01881789 Transplant ineligible Oprozomib lenalidomide dexamethasone Oprozomib cyclophosphamide dexamethasone August 2016
NCT02072863 Transplant ineligible Oprozomib melphalan prednisone October 2015
www.clinicaltrials.gov, Accessed April 2014.
48
Case 3 (from the practice of Ms Richards)

• An 85-year-old Vietnamese man was diagnosed with
  MM in February 2013 and received
  melphalan/prednisone/thalidomide with the
  melphalan being discontinued due to episodes of
  neutropenia
• In August 2013 he switched treatment centers and
  began receiving bortezomib/dexamethasone, which
  resulted in a response
• However, therapy was stopped because of
  peripheral neuropathy
• The patient experienced disease progression and
  is currently responding to carfilzomib/dexamethaso
  ne
• He speaks no English and his daughter, who comes
  with him for clinic visits, insists on
  translating for him

49
Patient Serum Paraprotein Levels During Treatment
Course
8.04
7.24
Bortezomib/Dexamethasone
6.43
5.63
4.82
4.02
g/dL
3.22
Carfilzomib/Dexamethasone
2.41
1.61
.8
3/5/2014
7/26/2013
2/6/2014
4/22/2014
8/23/2013
9/20/2013
10/18/2013
11/14/2013
12/12/2013
1/9/2014
Date
50
Preferred Induction Regimens Transplantation
Ineligible

• Rd Lenalidomide/low-dose dexamethasone
• VD Bortezomib/dexamethasone
• MPV Melphalan/prednisone/bortezomib
• MPR Melphalan/prednisone/lenalidomide
• MPT Melphalan/prednisone/thalidomide

NCCN. Clinical practice guidelines in oncology
multiple myeloma. v.2.2014.
51
The diminishing role of melphalan for older
patients Implications of the FIRST trial (ASH
2013) comparing Rd (lenalidomide/low-dose
dexamethasone) to MPT (melphalan/prednisone/thalid
omide)
Discussion Point
52
Phase III FIRST Trial Design
Rd until progression (n 535)
Eligibility (n 1,623)
Symptomatic NDMM Transplant ineligible or 65 years old Renal impairment allowed, but patients requiring dialysis excluded
111
R
Rd for 18 cycles (Rd18) (n 541)
MPT for 12 cycles (n 547)
R 25 mg d1-21, every 4 weeks d 40 mg d1, 8, 15,
22, every 4 weeks M 0.25 mg/kg d1-4, every 6
weeks P 2 mg/kg d1-4, every 6 weeks T 200 mg
d1-42, every 6 weeks

• Primary endpoint PFS
• Patients were stratified by age, country and ISS
  stage.

Facon T et al. Proc ASH 2013Abstract 2.
53
FIRST Progression-Free Survival
Median PFS
Rd (n 535) 25.5 mo
Rd18 (n 541) 20.7 mo
MPT (n 547) 21.2 mo
100
80
Hazard ratio Rd vs. MPT 0.72 p 0.00006
Rd vs. Rd18 0.70 p 0.00001 Rd18 vs.
MPT 1.03 p 0.70349
60
Patients ()
40
20
72 wks
0
Time (months)
With permission from Facon T et al. Proc ASH
2013Abstract 2.
54
An otherwise healthy 77-year-old patient presents
with fatigue. Workup reveals Hb 9.0 g/dL, normal
renal function, an M-spike with an IgG lambda
component of 4.9 g/dL and bone marrow consistent
with MM (ISS Stage II). Conventional
cytogenetics, FISH and skeletal survey are
normal. The patient is not eligible for
transplant. Which induction treatment would you
most likely recommend for this patient?
of respondents
Any regimen containing melphalan 22
Research To Practice Patterns of Care Study 2014
(N 101 practicing oncologists)
55
Preemptive dose reductions for older patients
RVD lite and other regimens
Discussion Point
56
Preemptive Dose Reductions for Patients of
Advancing Age
Agent DOSE LEVEL 0 DOSE LEVEL -1 DOSE LEVEL -2
Dexamethasone 40 mg/dd 1, 8, 15, 22 / 4 wk 20 mg/d d 1, 8, 15, 22 / 4 wk 10 mg/d d 1, 8, 15, 22 / 4 wk
Melphalan 0.25 mg/kg or 9 mg/m2d 1-4 / 4-6 wk 0.18 mg/kg or 7.5 mg/m2d 1-4 / 4-6 wk 0.13 mg/kg or 5 mg/m2d 1-4 / 4-6 wk
Thalidomide 100 mg/d 50 mg/d 50 mg qod
Lenalidomide 25 mg/d d 1-21 / 4 wk 15 mg/d d 1-21 / 4 wk 10 mg/d d 1-21 / 4 wk
Bortezomib 1.3 mg/m2 twice weeklyd 1, 4, 8, 11 / 3 wk 1.3 mg/m2 once weeklyd 1, 8, 15, 22 / 5 wk 1.3 mg/m2 once weeklyd 1, 8, 15, 22 / 5 wk
Prednisone 60 mg/m2 d 1-4 or 50 mg qod 30 mg/m2 d 1-4 or 25 mg qod 15 mg/m2 d 1-4 or 12.5 mg qod
Cyclophosphamide 100 mg/dd1-21 / 4 wk or 300 mg/m2/dd 1, 8, 15 / 4 wk 50 mg/dd1-21 / 4 wk or 150 mg/m2/dd 1, 8, 15 / 4 wk 50 mg/dd1-21 / 4 wk or 75 mg/m2/dd 1, 8, 15 / 4 wk
Palumbo A et al. Blood 20111184519-29.
57
Two Patients with Relapsed Multiple Myeloma

• 74 yo man with relapsed multiple myeloma and
  early signs of dementia (Ms Gleason)
• 64 yo man with relapsed mutliple myeloma who is
  experiencing corticosteroid-related symptoms (Ms
  Richards)

58
Case 4 (from the practice of Ms Gleason)

• A 74-year-old man diagnosed with MM in 2007
  received RVD followed by ASCT and lenalidomide
  maintenance, which was discontinued due to
  cognitive changes and early signs of dementia
• He was observed off therapy and experienced
  disease progression, at which time carfilzomib
  was initiated

59
Evaluation and workup of patients with MM and
altered mental status
Discussion Point
60
Single-agent versus combination therapy in the
relapsed setting selection and sequencing of
agents
Discussion Point
61
Phase I/II Dose Expansion Of a Multi-Center Trial
Of Carfilzomib and Pomalidomide With
Dexamethasone (Car-Pom-d) In Patients With
Relapsed/Refractory Multiple Myeloma (RRMM)
Target accrual (n 82)
Patients with RRMM Prior Len with 25 response/progression during Tx or 60 d after completion of regimen containing Len at full dose or MTD for 2 cycles
Carfilzomib Pomalidomide Dexamethasone
Overall response rate 55/79 (70) Median PFS
9.7 months Median OS Not yet reached.
Shah JJ et al. Proc ASH 2013Abstract 690
62
IMiDs
Thalidomide
Teratogenicity, peripheral neuropathy,
constipation, sedation, rash, VTE Oral 100-200
mg/d
Lenalidomide
MyelosuppressionVTE Oral 15-25 mg/d
Pomalidomide
MyelosuppressionVTE Oral 1-4 mg/d
63
Phase III MM-003 Trial Design
POM LoDEX (n 302) POM 4 mg/d, d1-21 LoDEX 40 mg (75 y) 20 mg (gt75 y) d1, 8,15, 22 (28-d cycle)
Eligibility (n 455)
Primary refractory or relapsed and refractory MM At least 2 prior therapies Failed LEN and BORT
R
HiDEX (n 153) 40 mg (75 y) 20 mg (gt75 y) d1-4, 9-12, 17-20 (28-d cycle)
PFS 50 reduction in risk of disease progression
OS 28 reduction in risk of death
Dimopoulos MA et al. Proc ASH 2013Abstract 408.
64
Select Adverse Events (AEs)
Grade 3/4 AEs POM LoDEX (n 300) HiDEX (n 149)
Hematologic Neutropenia Febrile neutropenia Anemia Thrombocytopenia 49 9 33 22 17 0 39 26
Nonhematologic Infections DVT/PEPeripheral neuropathy 33 11 25 01
San Miguel JF et al. Proc ASH 2013Abstract 686.
65
Management of MM bone disease Role of
kyphoplasty, radiation therapy and/or
bisphosphonates
Discussion Point
66
Case 5 (from the practice of Ms Richards)

• A 64-year-old engineer and active runner
  developed chronic foot pain that led to an MRI,
  which demonstrated a lytic lesion in the foot.
  Bone survey revealed multiple lytic lesions, and
  bone marrow biopsy confirmed the diagnosis of MM
• The patient received CyBorD (with subcutaneous
  bortezomib) followed by ASCT but preferred not to
  receive maintenance therapy
• Eighteen months later he developed sternal pain,
  and a PET-CT showed uptake in the sternum, which
  was proven to be nonsecretory MM
• He was restarted on CyBorD and is responding
  again
• He has become hyperactive and unable to sleep due
  to corticosteroids and sends multiple emails at
  night to the clinical staff

67


68
Bisphosphonates in patients without documented
bone disease duration of treatment
Discussion Point
69
Other agents and strategies under investigation
in relapsed/refractory MM Monoclonal antibodies
alone or with IMiDs
Discussion Point
70
Other Agents Under Investigation in
Relapsed/Refractory MM

• Proteasome inhibitors
• Marizomib
• Ixazomib
• Oprozomib
• Histone deacetylase (HDAC) inhibitors
• Panobinostat
• Vorinostat
• ACY-1215
• Monoclonal antibodies
• Elotuzumab
• Siltuximab
• Indatuximab ravtansine (BT062)
• Daratumumab
• Pidilizumab
• Tabalumab

• Signal transduction modulators/protein kinase
  inhibitors
• Masitinib mesylate
• Ibrutinib
• Palbociclib
• Ganetespib
• Trametinib
• Kinesin spindle protein inhibitor
• ARRY-520

www.clinicaltrials.gov, Accessed April 2014.