Transcript Challenging Cases in Multiple Myeloma

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Challenging Cases in
Multiple Myeloma
Oncologist and Nurse Investigators
Consult on Actual Patients from the
Practices of the Invited Faculty
Saturday, May 3, 2014
6:00 AM – 7:30 AM
Faculty
P Leif Bergsagel, MD
Jeffrey L Wolf, MD
Charise L Gleason, MSN,
ANP-C, AOCNP
Tiffany Richards, MS,
ANP-BC, AOCNP
Moderator
Neil Love, MD
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
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
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)
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)
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)
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
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
Discussion Point
Potential curability of MM; correlation
between depth of response and longterm outcome
Getting to Minimal Residual Disease (MRD)
Newly diagnosed
S.S. Patient
Disease burden
CR
1×108
Stringent CR
1×104
Molecular/Flow CR
?Cure?
0.0
1×1012
Discussion Point
Role of common genetic abnormalities
in patient risk assessment and
therapeutic decision-making
mSMART:
Mayo Stratification for Myeloma and
Risk-Adapted Therapy
High-Risk 20%
• FISH
- Del 17p
- t(14;16)
- t(14;20)
• GEP
- High-risk
Intermediate-Risk 20%
• FISH
- t(4;14)
• Cytogenetic
deletion 13 or
hypodiploidy
• PCLI ≥3%
Standard-Risk 60%
All others including:
• Hyperdiploidy
• t(11;14)
• t(6;14)
signature
3 years
4-5 years
Mikhael JR et al. Mayo Clin Proc 2013;88(4):360-76.
8-10 years
Discussion Point
Rationale for the use of 3-drug
combinations (versus 2) in the
induction setting
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.
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)
Phase III Noninferiority Trial of Subcutaneous
versus Intravenous Bortezomib
SubQ Bortezomib
2:1
N = 222
Relapsed MM
(n = 148)
R
1-3 prior lines of therapy
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 2011;12(5):431-40.
Arnulf B et al. Haematologica 2012;97(12):1925-8.
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)
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 quadrant
or between
– Right and left thigh
– Proximal and distal sites
Moreau P et al. Proc ASH 2010;Abstract 312.
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 2011;12(5):431-40.
Moreau P et al. Proc ASH 2010;Abstract 312.
Discussion Point
Preventing herpes zoster reactivation
in patients who are receiving
bortezomib
Discussion Point
Thromboprophylaxis in patients
receiving IMiDs; other side effects;
assessment of adherence to oral
medications
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 2008;22(2):414-23.
Discussion Point
Post-transplant consolidation and
maintenance therapy; impact of
cytogenetic profile
N Engl J Med 2012;366:1782-91.
N Engl J Med 2012;366:1770-81.
Post-Transplant Maintenance Lenalidomide
Study Details
IFM 2005-021
(Median follow-up 67 mo)
CALGB-1001042
(Median follow-up 34 mo)
1 Attal
n
Treatment
307
Lenalidomide
PFS
46 mo
307
Placebo
24 mo
81 mo
231
Lenalidomide
TTP
46 mo
Median OS
Not reached
229
Placebo
27 mo
73 mo
M et al. Proc ASH 2013;Abstract 406.
PL et al. N Engl J Med 2012;366:1770-81.
2 McCarthy
Outcome
Median OS
82 mo
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)
Discussion Point
Risk of second cancers in patients
receiving lenalidomide
IFM 2005-02: Second Primary Cancers (SPMs)
Lenalidomide
(n = 306)
Placebo
(n = 302)
13 (4%)
5 (2%)
Solid tumors
10 (3%)
4 (1%)
Nonmelanoma skin cancer
5 (2%)
3 (1%)
Total
26 (8%)
11 (4%)
Type of lesion
Hematologic cancer
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 2012;366(19):1782-91.
CALGB-100104: Disease Progression and
Second Primary Cancers
Outcome
Lenalidomide
Placebo
66%
39%
Lenalidomide
Placebo
Hematologic
8 (3.5%)
1 (0.4%)
Solid tumors
10 (4.3%)
5 (2.2%)
3-year PFS
Second primary cancers
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 < 0.001).
McCarthy PL et al. N Engl J Med 2012;366(19):1770-81.
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 2012;366(19):1770-81.
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
Patient Serum Paraprotein Levels After RVD
and Transplant
2.16
Bortezomib/Lenalidomi
de/Dexamethasone
1.94
1.73
1.51
1.08
.86
.65
Transplant
.43
3/19/2014
2/6/2014
12/26/2013
Date
11/14/2013
10/4/2013
8/23/2013
7/12/2013
6/1/2013
4/20/2013
.22
3/9/2013
g/dL
1.3
Discussion Point
Novel proteasome inhibitors
in the management of MM
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 2000;18:109-21. 2 Physiol Rev 2002;82:373-428. 3 Sci Am 2001;284:63-73. 4 Cell 1998;92:367-84.
Discussion Point
Available data on carfilzomib as part
of up-front induction therapy and in
the relapsed setting
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 2012;120(14):2817-25.
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 2012;120(14):2817-25.
Phase I/II Study of Front-Line Carfilzomib (CFZ) in
Combination with Lenalidomide and Dexamethasone
CRd
Induction
Transplanteligible and
ineligible
patients
CRd Cycles 1–4
CRd Cycles 5–8
CRd
Maintenance
Continued
lenalidomide
recommended
(off protocol)
CRd Cycles 9–24
LEN Cycles 25+
Transplant-eligible
with ≥PR
may undergo ASCT
• After a median of 12 cycles:
-
nCR = 62%
• Grade ≥3 PN = 0%
Jakubowiak AJ et al. Blood 2012;120(9):1801-9.
sCR = 42%
Phase III ECOG-E1A11 Trial
Trial Identifier: NCT01863550
Estimated enrollment: 756 (open)
Eligibility
Carfilzomib + lenalidomide +
low-dose dexamethasone 
lenalidomide maintenance*
Newly diagnosed standard-risk
MM
ECOG PS 0-2
R
No history of Grade ≥2
peripheral neuropathy
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.
Discussion Point
Incidence and management of
carfilzomib-associated peripheral
neuropathy
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 2012;120(14):2817-25.
Discussion Point
Other rare but important toxicities
with carfilzomib: pulmonary
hypertension and cardiac events
Discussion Point
Oral proteasome inhibitors in
development (ixazomib, oprozomib)
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
Ixazomib
Bortezomib
Adapted from Fostier K et al. OncoTargets and Therapy 2012;5:237-44.
Phase I/II Study of Weekly Ixazomib Combined with
Lenalidomide and Dexamethasone in Previously
Untreated MM
Maintenance
Induction: up to 12 x 28-day treatment cycles
1
8
15
22
MLN9708
MLN9708
MLN9708
Dex 40 mg
Dex 40 mg
Dex 40 mg
28
MLN9708
Dex 40 mg
maintenance
Days 1, 8, 15
Lenalidomide 25 mg, days 1–21
• ORR = 92%
• Grade 3 PN = 3%
Kumar SK et al. Proc ASH 2012;Abstract 332.
28-day cycles
≥VGPR = 55%
Ongoing Phase I/II Trials of Oprozomib in Newly
Diagnosed MM
Trial Identifier
Clinical Setting
Treatment Arms
Estimated
Primary
Completion
Date
Oprozomib +
lenalidomide +
dexamethasone
NCT01881789
Transplant ineligible
August 2016
Oprozomib +
cyclophosphamide +
dexamethasone
NCT02072863
Transplant ineligible
www.clinicaltrials.gov, Accessed April 2014.
Oprozomib +
melphalan +
prednisone
October 2015
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/dexamethasone
• He speaks no English and his daughter, who comes
with him for clinic visits, insists on translating for him
Patient Serum Paraprotein Levels During
Treatment Course
8.04
7.24
Bortezomib/Dexamethasone
6.43
5.63
4.02
3.22
Carfilzomib/Dexamethasone
2.41
1.61
Date
4/22/2014
3/5/2014
2/6/2014
1/9/2014
12/12/2013
11/14/2013
10/18/2013
9/20/2013
8/23/2013
.8
7/26/2013
g/dL
4.82
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.
Discussion Point
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/thalidomide)
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
1:1:1
R
Rd for 18 cycles (Rd18)
(n = 541)
MPT for 12 cycles
(n = 547)
R: 25 mg d1-21, every 4 weeks
• Primary endpoint: PFS
d: 40 mg d1, 8, 15, 22, every 4 weeks
• Patients were stratified by age,
country and ISS stage.
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
Facon T et al. Proc ASH 2013;Abstract 2.
FIRST: Progression-Free Survival
Median PFS
100
Rd
Patients (%)
80
(n = 535)
25.5 mo
Rd18 (n = 541)
20.7 mo
MPT (n = 547)
21.2 mo
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
40
72 wks
20
0
0
6
12
18
24
30
36
Time (months)
With permission from Facon T et al. Proc ASH 2013;Abstract 2.
42
48
54
60
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)
Discussion Point
Preemptive dose reductions for older
patients; “RVD lite” and other
regimens
Preemptive Dose Reductions for Patients of
Advancing Age
Agent
DOSE LEVEL 0
DOSE LEVEL -1
DOSE LEVEL -2
40 mg/d
d 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
0.25 mg/kg or 9 mg/m2
d 1-4 / 4-6 wk
0.18 mg/kg or 7.5 mg/m2
d 1-4 / 4-6 wk
0.13 mg/kg or 5 mg/m2
d 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 weekly
d 1, 4, 8, 11 / 3 wk
1.3 mg/m2 once weekly
d 1, 8, 15, 22 / 5 wk
1.3 mg/m2 once weekly
d 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
100 mg/d
d1-21 / 4 wk or
300 mg/m2/d
d 1, 8, 15 / 4 wk
50 mg/d
d1-21 / 4 wk or
150 mg/m2/d
d 1, 8, 15 / 4 wk
50 mg/d
d1-21 / 4 wk or
75 mg/m2/d
d 1, 8, 15 / 4 wk
Dexamethasone
Melphalan
Cyclophosphamide
Palumbo A et al. Blood 2011;118:4519-29.
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)
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
Discussion Point
Evaluation and workup of patients with
MM and altered mental status
Discussion Point
Single-agent versus combination
therapy in the relapsed setting;
selection and sequencing of agents
Phase I/II Dose Expansion Of a Multi-Center Trial Of
Carfilzomib and Pomalidomide With Dexamethasone (Car-Pomd) 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
Overall response rate: 55/79 (70%)
Median PFS: 9.7 months
Median OS: Not yet reached.
Shah JJ et al. Proc ASH 2013;Abstract 690
Carfilzomib
+
Pomalidomide
+
Dexamethasone
IMiDs
Thalidomide
O
O
H
N
O
N
Teratogenicity, peripheral
neuropathy, constipation, sedation,
rash, VTE
Oral 100-200 mg/d
O
Lenalidomide
O
O
H
N
N
O
Myelosuppression
VTE
Oral 15-25 mg/d
NH2
Pomalidomide
O
N
NH2
O
O
H
N
O
Myelosuppression
VTE
Oral 1-4 mg/d
Phase III MM-003 Trial Design
Eligibility (n = 455)
Primary refractory or relapsed
and refractory MM
R
At least 2 prior therapies
Failed LEN and BORT
POM + LoDEX (n = 302)
POM: 4 mg/d, d1-21
LoDEX: 40 mg (≤75 y)
20 mg (>75 y)
d1, 8,15, 22 (28-d cycle)
HiDEX (n = 153)
40 mg (≤75 y)
20 mg (>75 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 2013;Abstract 408.
Select Adverse Events (AEs)
POM + LoDEX
(n = 300)
HiDEX
(n = 149)
49%
17%
9%
0%
Anemia
33%
39%
Thrombocytopenia
22%
26%
Infections
33%
25%
DVT/PE
Peripheral neuropathy
1%
1%
0%
1%
Grade 3/4 AEs
Hematologic
Neutropenia
Febrile neutropenia
Nonhematologic
San Miguel JF et al. Proc ASH 2013;Abstract 686.
Discussion Point
Management of MM bone disease:
Role of kyphoplasty, radiation therapy
and/or bisphosphonates
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
Discussion Point
Bisphosphonates in patients without
documented bone disease;
duration of treatment
Discussion Point
Other agents and strategies under
investigation in relapsed/refractory
MM: Monoclonal antibodies alone or
with IMiDs
Other Agents Under Investigation in
Relapsed/Refractory MM
Proteasome inhibitors
•
Marizomib
Signal transduction modulators/
protein kinase inhibitors
•
Ixazomib
•
Masitinib mesylate
•
Oprozomib
•
Ibrutinib
•
Palbociclib
•
Ganetespib
•
Trametinib
Histone deacetylase (HDAC) inhibitors
•
Panobinostat
•
Vorinostat
•
ACY-1215
Monoclonal antibodies
•
Elotuzumab
•
Siltuximab
•
Indatuximab ravtansine (BT062)
•
Daratumumab
•
Pidilizumab
•
Tabalumab
www.clinicaltrials.gov, Accessed April 2014.
Kinesin spindle protein inhibitor
•
ARRY-520