InternatIonal MyeloMa FoundatIon
ASH 2011
Multiple Myeloma
Highlights
Summaries of Multiple Myeloma Presentations
from the 53rd Annual Meeting
of the American Society for Hematology (ASH)
held in San Diego, California
December 1013, 2011
ASH 2011 Summaries of Multiple Myeloma Presentations
ASH 2011 brought the greatest number of abstracts on mul-
Prashant Kapoor's analysis of survival among patients
tiple myeloma (MM) ever published in the meeting's his-
45 years of age or less at the time of diagnosis in
tory, 712 abstracts to be exact. While no single abstract made
the era of novel therapies concludes that younger
headlines, taken collectively they offer ample evidence of a
patients not only benefit from the survival advantage
year of significant steps forward in understanding, prognos-
granted by their youth and general good health, but
ticating, imaging, treating, and monitoring this disease. To
from exposure to novel agents, as opposed to their
better categorize the meeting's highlights, we turn to the
historical controls.
IMF's 10 STEPS TO BETTER CARETM as a framework.
· Survival outcome of young myeloma patients in the era
1. Know What You're Dealing With
of novel therapy (Prashant Kapoor, Mayo Clinic, Roches-
ter, MN, USA, abstract #2950).
Several important abstracts were presented in this general
category of diagnosis and disease definition, notably a series
Another significant presentation in this category was the
of studies from the Mayo Clinic, Rochester, MN, USA, that
follow-up on the study of therapy for high-risk smoldering
examine outcomes among various subgroups of patients.
multiple myeloma (SMM) by Maria-Victoria Mateos, of the
University of Salamanca, Salamanca, Spain. Dr. Mateos's lon-
Shaji Kumar examined the outcomes of patients in the US,
ger-term data now indicate that time to progression to active
Europe, and Korea who became refractory to both bortezo-
MM was significantly prolonged in the group of patients
mib and an immunomodulatory agent. He points out that
with high-risk smoldering disease that was treated with nine
these "double refractory" patients have a poor prognosis no
cycles of lenalidomide (Revlimid®) and dexamethasone fol-
matter where they are treated, with median overall survival
lowed by lenalidomide maintenance. The median time to
at 13 months in the US, 7 months in Europe, and 8 months
progression to active disease in the untreated group was 25
in Korea. Patients in the US are likely to have more therapies
months, whereas the median has not been reached in the
both before and after they become refractory.
treated group. Only two patients developed second primary
malignancies in the treated group, and both malignancies
· Differences in patterns of therapy and outcomes among
were confirmed to have originated before the start of len/
patients in the US, Europe, and Asia (Dr. Shaji Kumar,
dex therapy. While there is a trend to improved overall sur-
Mayo Clinic, Rochester, MN, USA, abstract #3989)
vival in the treated group, it is too early to fully assess over-
Vishal Rana's study looking at the reasons for early mortality
all survival benefit, and therefore it is too early to change
among those who died within twelve months of diagnosis
clinical practice based on these trial results.
concludes that advanced age, poor performance status, high
ISS stage, and high levels of serum calcium are predictors
·Smoldering myeloma (SMM) at high risk of progression
of early death. Identifying these factors up front will enable
to symptomatic disease (Maria-Victoria Mateos, Hospital
doctors to design risk-adapted, appropriate therapy.
Clinico Universitario, Salamanca, Spain, abstract #991).
·Factors predicting early mortality in patients with newly
2. Tests You Really Need
diagnosed multiple myeloma (Vishal Rana, Mayo Clinic,
Data in the category of valuable prognostic tests includes
Rochester, MN, USA, abstract #3981)
the new heavy/light chain assay, genetic studies, imaging
Soo-Mee Bang retrospectively examined outcomes in
studies, and flow cytometry. Of particular note is the iden-
patients over 70 years of age, concluding that exposure to
tification of an IMiD-binding protein on the surface of MM
novel agents has improved their overall survival, although it
cells, cereblon, which corresponds to response to treatment
still lags behind that of younger patients.
with IMiD therapies.
· Treatment patterns and outcomes in elderly patients
·Cereblon Expression Is Required for the Anti-Myeloma
(Soo-Mee Bang, Mayo Clinic, Rochester, MN, USA,
Activity of Lenalidomide and Pomalidomide ( Yuan Xiao
abstract #3980)
Zhu, Mayo Clinic, Scottsdale, AZ, USA, abstract #127)
3
·High Expression of the Thalidomide-Binding Pro-
patients >65 years, he discovered a much lower incidence
tein Cereblon (CRBN) Is Associated with Improved
of t(4;14) in this group, but no significant difference in the
Clinical Response in Patients with Multiple Myeloma
occurrence of del(13) or del(17p). As in younger patients,
Treated with Lenalidomide and Dexamethasone (Daniel
both t(4;14) and del(17p) negatively affect PFS and OS in
Heintel, University Hospital Vienna, Vienna, Austria,
elderly patients.
abstract #2879)
·Gene Mutations Detected by Whole-Exome Sequencing
Elena Zamagni's prospective study confirms that PET-
and Recurrent Cytogenetic Abnormalities Are Indepen-
defined CR is an independent prognostic factor in MM
dent Events in Multiple Myeloma (Herve Avet-Loiseau,
patients treated with up-front novel therapies and autolo-
University Hospital, Nantes, France, abstract #1816)
gous transplant. Jens Hillengass from the Heidelberg group
reports that the number of focal lesions on whole-body MRI
·Incidence and Prognostic Value of Chromosomal Abnor-
has prognostic value after autologous transplant, but not
malities in Elderly Patients with myeloma: The IFM Expe-
at diagnosis. Whole-body MRI is not able to discern focal
rience on 1095 Patients (Herve Avet-Loiseau, University
lesions with active MM cells as opposed to osteolyses with-
Hospital, Nantes, France, abstract #994)
out active MM.
·SNP-Based Mapping Arrays Reveal High Genomic Com-
plexity in Monoclonal Gammopathies: From the MGUS
·Conventionally-Defined and PET/CT-Defined Complete
to Myeloma Status (Lucia Lopez-Corral, University Hos-
Response (CR) to Novel Agent-Based Induction Therapy
pital Salamanca, Salamanca, Spain, abstract #295)
and Autologous Stem-Cell Transplantation (ASCT) In
Multiple Myeloma (MM): A Prospective Study of Clinical
·Combining Information Regarding Chromosomal Aber-
and Prognostic Implications (Elena Zamagni, University
rations t(4;14), Del(17p13) and the Copy Number of
of Bologna, Bologna, Italy, abstract #826)
1q21 with the International Staging System Classifica-
tion Allows Stratification of Myeloma Patients Under-
·Prognostic Significance of the Number of Focal Lesions
going Autologous Stem Cell Transplantation: Results
in Whole Body Magnetic Resonance Imaging Before and
From the HOVON-65/GMMG HD4 Trial (Kai Neben,
After Autologous Stem Cell Transplantation (Jens Hill-
University Hospital Heidelberg, Heidelberg, Germany,
engass, University of Heidelberg, Heidelberg, Germany,
abstract #332)
abstract #1812)
·A 41-Gene Signature Predicts Complete Response (CR)
The serum heavy/light assay, which Heinz Ludwig describes
to Bortezomib-Thalidomide-Dexamethasone (VTD)
as a "simple test," is able to measure the relationship
As Induction Therapy Prior to Autologous Stem-Cell
between clonal and non-clonal protein in the blood. It
Transplantation (ASCT) in Multiple Myeloma (Caro-
increases diagnostic accuracy by allowing the measurement
lina Terragna, University of Bologna, Bologna, Italy,
of paraproteins that cannot be measured via other tech-
abstract #805)
niques, especially in the case of IgA, which tends to migrate
to the beta region with serum protein electrophoresis.
Roberto Pessoa Magalhaes of the Salamanca group per-
It can also identify those patients who are not in true CR,
formed a novel flow cytometric analysis of patients with
despite evidence to the contrary with immunofixation elec-
long-term disease control. He reported that these patients
trophoresis (IFE).
have increased numbers of cytotoxic T-cells and CD56 natu-
ral killer (NK) cells.
·Serum Heavy/Light Chain and Free Light Chain Measure-
ments Provide Prognostic Information, Allow Creation of
·Multidimensional Flow Cytometric (MFC) Analysis of
a Prognostic Model and Identify Clonal Changes (clonal
the Immune System of Multiple Myeloma (MM) Patients
tiding) Through the Course of Multiple Myeloma (MM).
Achieving Long Term Disease Control (Roberto Pessoa
(Heinz Ludwig, University Hospital Vienna, Vienna, Aus-
Magalhaes, University of Salamanca, Salamanca, Spain,
tria, abstract #2883)
abstract #810
Herve Avet-Loiseau compared data from whole exome
3. Initial Treatment Options
sequencing and cytogenetics and discovered that there was
no significant correlation between recurrent chromosomal
Survival continues to improve for newly diagnosed patients.
changes and gene mutations. There was also no correlation
Better induction therapy improves survival. Jesús San
between the number of genetic mutations and cytogenetic
Miguel's 5-year follow-up data on the VISTA trial (VP vs.
risk. In his study of chromosomal abnormalities in MM
VMP) demonstrated an overall survival benefit of 13 months,
4
with a 31% reduced risk of death for those on VMP vs. MP.
Nikhil Munshi, of the Dana-Farber Cancer Institute in
Although VMP did not overcome cytogenetic risk, patients
Boston, reinforced the theme of "less is more" in the
who relapsed on VMP and went on to other therapy still did
elderly population with his study confirming the effi-
better on their second therapy than those on MP did. There
cacy and tolerability of once-weekly bortezomib with
was no increased risk of second malignancies with VMP.
dexamethasone.
·Continued Overall Survival Benefit After 5 Years' Fol-
·Once a Week Bortezomib with Dexamethasone Is Effec-
low-up with Bortezomib-Melphalan-Prednisone (VMP)
tive with Limited Toxicity in Newly Diagnosed Multiple
Versus Melphalan-Prednisone (MP) in Patients with Pre-
Myeloma Patients with Older Age and Co-Morbidities
viously Untreated Multiple Myeloma, and No Increased
(Nikhil Munshi, Dana-Farber Cancer Institute, Boston,
Risk of Second Primary Malignancies: Final Results of
MA, USA, abstract #3964)
the Phase 3 VISTA Trial (Jesús San Miguel, University
·The Improved Efficacy of Bortezomib-Containing Induc-
Hospital Salamanca, Salamanca, Spain, abstract #476)
tion Regimens (BCIR) Versus Non-Bortezomib Contain-
Philippe Moreau of the IFM presented data on the PK and
ing Induction Regimens (NBCIR) in Transplant-Eligible
PD of subcutaneous bortezomib (Velcade®), demonstrating
Patients with Multiple Myeloma (MM): Meta-Analysis of
that it has similar pharmacokinetics and pharmacodynamics
Phase III Randomized Controlled Trials (Ajay Nooka,
to intravenous bortezomib. Site of injection (thigh or abdo-
Winship Cancer Institute of Emory University, Atlanta,
men) had no impact.
GA, USA, abstract #3994)
·Pharmacokinetics (PK) and Pharmacodynamics (PD)
·An Alternate Day Dosing Strategy for Lenalidomide in
of Subcutaneous Versus Intravenous Administration of
Multiple Myeloma Improves Cost-Effectiveness Whilst
Bortezomib in Patients with Relapsed Multiple Myeloma:
Maintaining Efficacy (Rakesh Popat, UCL Cancer Insti-
Effects of Subcutaneous Injection Site and Concentra-
tute, London, United Kingdom, abstract #4201)
tion, and Patient Characteristics (Phillippe Moreau, Uni-
versity Hospital, Nantes, France, abstract #1863)
4. Supportive Care and How to Get It
Data in this category include details about peripheral neu-
Ruben Niesvizky's UPFRONT study comparing VD, VTD, and
ropathy, venous thromboembolism, renal impairment, and
VMP in nearly 500 newly diagnosed patients age >65 years
the risk factors for the development of second primary
in the community practice setting demonstrated that there
malignancies (SPMs).
is added toxicity and no significant benefit to triplet ther-
apy in an elderly population. There were increased rates of
Paola Tacchetti reviews the experience with bortezomib- and
hematologic toxicity with melphalan added to Velcade and
thalidomide- induced peripheral neuropathy (PN). An inter-
dexamethasone, and thalidomide increased the incidence of
esting new finding is the correlation between the likelihood
peripheral neuropathy. Similarly, Rachid Baz's retrospective
of PN and deregulated expression of genes (GEP) involving
study of doublets vs. triplets of novel agents indicated that
nervous system function from assessment of bone marrow
patients without high-risk cytogenetics had no difference in
plasma cells from patients with VTD-induced PN.
OS regardless of whether they had two-drug or three-drug
regimens. Those with high-risk cytogenetics, however, had
·Bortezomib- and Thalidomide-Induced Peripheral Neu-
worse survival with the intensive three-drug regimens than
ropathy (PN) in Multiple Myeloma (MM): Clinical and
with two-drug combinations.
Molecular Analysis of 474 Patients Treated with Thalid-
omide-Dexamethasone (TD) or Bortezomib-TD (VTD)
·Efficacy and Safety of Three Bortezomib-Based Combi-
(Paola Tacchetti, University of Bologna, Bologna, Italy,
nations in Elderly, Newly Diagnosed Multiple Myeloma
abstract #1821)
Patients: Results From All Randomized Patients in the
Community-Based, Phase 3b UPFRONT Study (Ruben
In the final analysis of risk factors for venous thrombo-
Niesvizky, Weill Cornell Medical College, New York, NY,
embolism, the French group noted increased risk in men,
USA, abstract #478)
with additional risk for smoking and use of erythropoietic
agents (Procrit® or Dorbapoietin®). Although prophylaxis is
·Outcomes Analysis of Doublets of Novel Agents with
required with IMiD-based therapy, it was not possible to dis-
Corticosteroids Versus Regimens with 3 or More Agents
criminate added value with low molecular-weight heparin
for Multiple Myeloma (MM): A Retrospective Analysis
(LMWH) versus use of aspirin, although there was a higher
(Rachid Baz, Moffitt Cancer Center, University of South
risk of bleeding episodes with aspirin use.
Florida, FL, USA, abstract #1878)
5
·Final Analysis of MELISSE, a Large Multicentric Observa-
risk except possibly lenalidomide when used along with con-
tional Study to Determine Risk Factors of Venous Throm-
ventional-dose melphalan (eg MPR regimen: abstract #475)
boembolism in Patients with Multiple Myeloma Treated
or as consolidation immediately after use of high-dose mel-
with Immunomodulator Drugs (Xavier Leleleu, Hopital
phalan (IFM 2005 study). Thus, timing and sequencing do
Claude Huriez, CHRU, Lille, France, abstract #1235)
seem to be important in adding to any potential underlying
The group from Greece showed that bortezomib-based regi-
host factors. But, two key points emerge.
mens act more rapidly than IMiD-based therapy in the set-
1. Any increased risk of SPMs is clearly offset by substantially
ting of renal insufficiency and are therefore the preferred
improved remission duration (as well as overall survival
choice in this situation for newly diagnosed patients.
for some studies). The onset of SPMs has not had a nega-
·The Role of Novel Agents on Reversibility of Renal
tive impact on overall survival in any of the studies.
Impairment in Newly Diagnosed Patients with Multiple
2.The development of SPMs is an important aspect of longer
Myeloma; a Single Center Experience on 112 Patients
survival,especiallyinmoreelderlyMMpatients.Appropriate
(Meletios Dimopoulos, University of Athens School of
monitoringandearlymanagementarenowcrucialaspectsof
Medicine, Athens, Greece, abstract #3961)
ongoing care.
The group from the University of Pittsburgh's careful review
Awareness is key: the amnesia is over! Regular monitoring
of serial bone marrow biopsies demonstrates that the use
(once or twice a year), for example utilizing whole body
of lenalidomide does not increase the likelihood of marrow
PET/CT scanning, can be a very effective way to assess the
dyspoiesis (MDS [myelodysplastic syndrome]).
ongoing status and risks.
·Longitudinal Evaluation of 110 Bone Marrow Aspirates
·Long-Term Outcomes and Safety of Continuous Lenalid-
of Multiple Myeloma Patients Treated with Lenalido-
omide Plus Dexamethasone (Len+Dex) Treatment
mide Alone or in Combination with Autologous Stem
in Patients (Pts) with Relapsed or Refractory Multiple
Cell Transplantation or Alkylators for Early Dysplastic
Myeloma (RRMM) (Meletios Dimopoulos, University of
Signs (Sara Monaghan, University of Pittsburgh, PA, USA,
Athens, Athens, Greece, abstract #2929)
abstract #2885)
·Risk of Second Primary Malignancies (SPMs) Follow-
The next series of papers evaluates the risk of development
ing Bortezomib (Btz)-Based Therapy: Analysis of Four
of second primary malignancies (SPMs) in patients with MM
Phase 3 Randomized Controlled Trials in Previously
at different disease stages, with different therapies and in a
Untreated or Relapsed Multiple Myeloma (MM) (Jesús
broad range of settings. It is clear that the MM community as
San Miguel, University of Salamanca, Salamanca, Spain,
a whole has emerged from its period of collective amnesia
abstract #2933)
on this topic of SPMs, which were first noted with the use of
melphalan therapy in the 1970s. The risk of SPMs is linked
·Second Malignancies in Total Therapy 3 Trials for Newly
both to host factors such as increasing age, male sex, and
Diagnosed Multiple Myeloma: Influence of Lenalido-
prior or family history of cancer, as well as to the impact of
mide Versus Thalidomide in Maintenance Phases (Saad
treatment. It is important to note that patients can present
Usmani, University of Arkansas for Medical Sciences,
with an additional second cancer (either hematologic such
Little Rock, AR, USA, abstract #823)
as MDS or leukemia or a solid cancer such as lung or breast
·Risks for Different Neoplasms (DNs) in Multiple Myeloma
cancer) simultaneous with (or shortly before) the diagnosis
(MM) Patients May Involve Specific Host-, Myeloma-
of active myeloma. This onset must be distinguished from
and Treatment-Related Susceptibilities: Registry Data
SPMs that emerge during the course of subsequent therapy.
of 681 Consecutive MM Patients (Martina Kleber, Uni-
It is helpful to look at the details of each study evaluating
versity of Freiburg Medical Center, Freiburg, Germany,
particular therapies. There continues to be an increased
abstract #3929)
risk with the use of melphalan as well as the DCEP regimen
(in the IFM 2005 study) as well as, possibly, double versus
·Second Malignancies Among Elderly Multiple Myeloma
single high-dose melphalan autotransplant. Bortezomib use
Patients Exposed to Bortezomib and Other Treatments:
does not appear to confer any added risk, as noted in the
An Analysis of the US SEER-Medicare Linked Database
newly presented data (abstracts #2933 and #3972). It is
(Dina Gifkins, Janssen Research & Development, Rari-
unclear if any of the novel agents confer any definite added
tan, NJ, USA, abstract #3972)
6
·Secondary Primary Malignancies in Patients with Mul-
Multiple Myeloma Undergoing Autologous Stem Cell
tiple Myeloma Treated with High-Dose Chemother-
Transplantation Following a Lenalidomide-Based Initial
apy and Autologous Blood Stem Cell Transplantation
Therapy (Shaji Kumar, Mayo Clinic, Rochester, MN, USA,
(Roland Fenk, Heinrich Heine University, Duesseldorf,
abstract #2992)
Germany, abstract #4087)
·Cost Analysis of Using Plerixafor Plus G-CSF Versus
·Second Primary Malignancies in Newly Diagnosed Mul-
Cyclophosphamide Plus G-CSF for Autologous Stem
tiple Myeloma Patients Treated with Lenalidomide: Anal-
Cell Mobilization in Multiple Myeloma Patients Treated
ysis of Pooled Data in 2459 Patients (Antonio Palumbo,
At Memorial Sloan-Kettering Cancer Center (MSKCC)
University of Torino, Torino, Italy, abstract #996)
(Nelly Adel, Pharmacy, Memorial Sloan-Kettering Cancer
Center, New York, NY, USA, abstract #4059)
5. Transplant: Do You Need One?
Transplant, even in this age of highly effective novel
6. Response Assessment
therapies, is still of great value in MM and will remain
Bruno Paiva of the Salamanca group identifies a group of
part of the standard of care for younger patients. Two
patients who require special monitoring and novel treat-
studies that tip the balance toward high-dose ther-
ment strategies after stem cell transplant.
apy and transplant were Antonio Palumbo's random-
ized comparison of MPR vs. transplant (MEL200) and
·High-Risk Cytogenetics and Persistent Minimal Resid-
Lijun Dai's trial of len/dex with and without ASCT. Both
ual Disease (MRD) by Multiparameter Flow Cytometry
studies conclude that although toxicities are higher with
(MFC) Predict Unsustained Complete Response (CR)
high-dose melphalan and stem cell transplant, the data does
After Autologous Stem Cell Transplantation (ASCT) in
suggest improved progression-free (Palumbo) and overall
Multiple Myeloma (MM) (Bruno Paiva, University of Sal-
(Dai) survival.
amanca, Salamanca, Spain, abstract #630)
·Melphalan/Prednisone/Lenalidomide
(MPR)
Versus
7. Consolidation and/or Maintenance
High-Dose Melphalan and Autologous Transplantation
The notion of continuous therapy for MM has gained cre-
(MEL200) in Newly Diagnosed Multiple Myeloma (MM)
dence as the result of several studies examining the role of
Patients <65 Years: Results of a Randomized Phase III
consolidation and maintenance therapy. PFS was doubled
Study (Antonio Palumbo, University of Torino, Torino,
in Antonio Palumbo's follow-up data on the MM 015 MPR-R
Italy, abstract #3069)
trial. In Maria-Victoria Mateos's trial using VT or VP main-
·A Randomized Clinical Trial of Lenalidomide and Dexa-
tenance after VTP or VMP, both VT and VP improved the
methasone with and without Autologous Stem Cell
complete response rate from 24% before to 42% after main-
Transplant in Patients with Newly Diagnosed Multiple
tenance. The IFM data on up-front VRD followed by ASCT,
Myeloma: Interim Study Results (Lijun Dai, University of
VRD consolidation, and lenalidomide maintenance led to an
Pittsburgh, PA, USA, abstract #4142)
impressive stringent complete response (sCR) rate of 38%.
Several studies examined the timing, route of adminis-
·A Phase 3 Study Evaluating the Efficacy and Safety of
tration, and cost of mobilizing stem cells with plerixafor
Lenalidomide (Len) Combined with Melphalan and
(Mozobil®), demonstrating that it can be given at a more
Prednisone Followed by Continuous Lenalidomide
convenient schedule, can be administered intravenously as
Maintenance (MPR-R) in Patients (Pts) 65 Years ( Yrs)
well as by injection, and that, though costly, it causes fewer
with Newly Diagnosed Multiple Myeloma (NDMM):
problems than cyclophosphamide and thereby reduces hos-
Updated Results for Pts Aged 65-75 Yrs Enrolled in
pitalization and overall healthcare costs.
MM-015 (Antonio Palumbo, University of Torino, Torino,
Italy, abstract #475)
·Temporal Changes in Plerixafor Administration Do Not
Impact Hematopoietic Stem Cell Mobilization Efficacy:
·Thalidomide As Maintenance Therapy in Multiple
Results of a Prospective Clinical Trial (R. Donald Harvey,
Myeloma (MM) Improves Progression Free Survival
Winship Cancer Institute of Emory University, Atlanta,
(PFS) and Overall Survival (OS): A Meta-Analysis (Ajay
GA, USA, abstract #2988)
Nooka, Winship Cancer Institute of Emory University,
Atlanta, GA, USA, abstract #1855)
·Phase II Trial of Intravenously Administered AMD3100
(Plerixafor) for Stem Cell Mobilization in Patients with
·Bortezomib, Lenalidomide, and Dexamethasone
7
(VRD) Consolidation and Lenalidomide Maintenance
·Impact of Global and Gene-Specific DNA Methylation
in Frontline Multiple Myeloma Patients: Updated
Pattern in Relapsed Multiple Myeloma Patients Treated
Results of the IFM 2008 Phase II VRD Intensive Program
with Bortezomib (Carlos Fernandez de Larrea, Univer-
(Marielle Roussel, Hôpital Purpan, Toulouse, France,
sity of Barcelona, Barcelona, Spain, abstract #132)
abstract #1872)
·Reversibility of the Resistance to Lenalidomide and
·Maintenance Therapy with Bortezomib Plus Thalidomide
Pomalidomide and Absence of Cross-Resistance in a
(VT) or Bortezomib Plus Prednisone (VP) In Elderly
Murine Model of MM (Enrique Ocio, University of Sala-
Myeloma Patients Included In the GEM2005MAS65
manca, Salamanca, Spain, abstract #134)
Spanish Randomized Trial (Maria-Victoria Mateos,
University Hospital Salamanca, Salamanca, Spain,
10. New Trials
abstract #477)
Probably the richest sources of new information at ASH this
·MRC Myeloma IX, 6 Year Median Follow-up (FU) High-
year were the sessions on results of new drugs in clinical
lights the Importance of Long-Term FU in Myeloma
trials. The most promising include the two drugs likely to be
Clinical Trials and Differential Effects of Thalidomide
approved by the FDA in the next calendar year, carfilzomib
in High- and Low-Risk Disease (Gareth Morgan, Insti-
and pomalidomide. In Andrzej Jakubowiak's phase I/II front-
tute of Cancer Research, London, United Kingdom,
line trial of carfilzomib in combination with lenalidomide
abstract #993)
and dexamethasone, 100% of patients had >/= VGPR after
4 cycles, with 71% of patients in CR after 4 cycles, and 79%
8. Monitoring without Mystery
in nCR/CR after 12 cycles. All patients were able to mobilize
Saad Usmani from the University of Arkansas provides com-
and harvest stem cells for future transplant successfully. The
pelling data on the utility of MRI and PET in predicting PFS
IFM and Dana-Farber data with pomalidomide and dexa-
and OS. Former IMF grant awardee Marco Ladetto of the
methasone in relapsed and refractory MM were also impres-
University of Torino presented data on the impact of mini-
sive. Other very promising results were from the studies of
mal residual disease (MRD) detected by real-time quantita-
the monocloncal antibody elotuzumab in combination with
tive polymerase chain reaction, and concluded that careful
lenalidomide and dexamethasone; bendamustine, an old
monitoring of increases in MRD can lead to tailored treat-
drug finding new life in combination with lenalidomide or
ment for those most at risk of relapse. In these patients, it is
bortezomib; and the novel proteasome inhibitors MLN9708,
crucial to make response as complete as possible.
given orally, and marizomib, given intravenously. Perhaps
most disappointing were the long-anticipated results of two
·Implications of Serial Magnetic Resonance Imaging and
studies of the HDAC inhibitor vorinostat (Zolinza®),which
Positron Emission Tomography Scanning for Survival of
showed only minimal benefit and significant toxicities.
Untreated Myeloma Patients Treated with Total Therapy
3 (Saad Usmani, University of Arkansas for Medical Sci-
·Final Results From the Bortezomib-naïve Group of
ences, Little Rock, AR, USA, abstract #3082)
PX-171-004, a Phase 2 Study of Single-Agent Carfilzomib
in Patients with Relapsed and/or Refractory MM (Ravi Vij,
·Long-Term Results of the GIMEMA VTD Consolidation
Washington University School of Medicine, Saint Louis,
TRIAL in Autografted Multiple Myeloma Patients (VEL-
MO, USA, abstract #813)
03-096): Impact of Minimal Residual Disease Detection
by Real Time Quantitative PCR on Late Recurrences and
·Final Results of a Frontline Phase 1/2 Study of Carfil-
Overall Survival. (Marco Ladetto, University of Torino,
zomib, Lenalidomide, and Low-Dose Dexamethasone
Torino, Italy, abstract #827)
(CRd) in Multiple Myeloma (MM) (Andrzej Jakubowiak,
University of Chicago, IL, USA, abstract #631)
9. Relapse: Do You Need A Change
·Carfilzomib Combined with Thalidomide and Dexa-
in Treatment?
methasone (CARTHADEX) As Induction Treatment Prior
Assessment of relapse with bortezomib and the IMiDs were
to High-Dose Melphalan (HDM) in Newly Diagnosed
the topics of two important studies. Carlos de Larrea from
Patients with Multiple Myeloma (MM). A Trial of the
the University of Barcelona identified a sub-group of bort-
European Myeloma Network EMN (Pieter Sonneveld,
ezomib-treated patients with poor prognosis due to DNA
Erasmus Medical Center, Rotterdam, The Netherlands,
methylation, while Enrique Ocio of the University of Sala-
abstract #633)
manca concludes that if a patient is resistant to one IMiD,
·Unfavorable Cytogenetic Characteristics Do Not
another IMiD can be effective and should be tried.
Adversely Impact Response Rates in Patients with
8
Relapsed and/or Refractory Multiple Myeloma Treated
of IFM 2009-02 (Xavier Leleu, Hopital Claude Huriez,
with Single-Agent Carfilzomib on the 003 (A1) Study
CHRU, Lille, France, abstract #812)
(Andrzej Jakubowiak, University of Chicago, IL, USA,
·Phase II Study of Carfilzomib (CFZ) Combined with
abstract #1875)
Other Anti-Myeloma Agents in Relapsed-Refractory
·The Novel KSP Inhibitor ARRY-520 Demonstrates Single-
Multiple Myeloma (RRMM) - Updates on the UARK
Agent Activity in Refractory Myeloma: Results From a
Compassionate Use Protocol (Saad Usmani, University
Phase 2 Trial in Patients with Relapsed/Refractory Multi-
of Arkansas for Medical Sciences, Little Rock, AR, USA,
ple Myeloma (MM) (Sagar Lonial, Winship Cancer Insti-
abstract #2947)
tute, Emory University School of Medicine, Atlanta, GA,
·Investigational Agent MLN9708, An Oral Proteasome
USA, abstract #2935)
Inhibitor, in Patients (Pts) with Relapsed and/or Refrac-
·T-Bird (thalidomide, clarithromycin/[Biaxin®], lenalido-
tory Multiple Myeloma (MM): Results From the Expan-
mide/[Revlimid®], Dexamethasone) Therapy in Newly
sion Cohorts of a Phase 1 Dose-Escalation Study (Paul
Diagnosed Symptomatic Multiple Myeloma (Tomer
Richardson, Dana-Farber Cancer Institute, Boston, MA,
Mark, Weill Cornell Medical College, New York, NY, USA,
USA, abstract #301)
abstract #2937)
·Weekly Dosing of the Investigational Oral Proteasome
·Preliminary Results of a Phase 2 Study of PD 0332991 in
Inhibitor MLN9708 in Patients with Relapsed and/or
Combination with Bortezomib and Dexamethasone in
Refractory Multiple Myeloma: Results From a Phase 1
Patients with Relapsed and Refractory Multiple Myeloma
Dose-Escalation Study (Shaji Kumar, Mayo Clinic, Roch-
(Ruben Niesvizky, Weill Cornell Medical College, New
ester, MN, USA, abstract #816)
York, NY, USA, abstract #2940)
·Phase 1/2 Study of Oral MLN9708, A Novel, Investi-
·Long Term Outcomes of Pomalidomide and Dexametha-
gational Proteasome Inhibitor, in Combination with
sone in Patients with Relapsed Multiple Myeloma: Analy-
Lenalidomide and Dexamethasone in Patients with Pre-
sis 4 Years After the Original Cohort (Joseph Mikhael,
viously Untreated Multiple Myeloma (Jesus Berdeja,
Mayo Clinic, Scottsdale, AZ, USA, abstract # 2942)
Mayo Clinic, Rochester, MN, USA, abstract #479)
·PomalidomideandDexamethasoneinRelapsedMyeloma:
·Phase 1 Clinical Evaluation of Twice-Weekly Marizomib
Results of 225 Patients Treated in Five Cohorts Over Three
(NPI-0052), a Novel Proteasome Inhibitor, in Patients
Years. (Martha Lacy, Mayo Clinic, Rochester, MN, USA,
with Relapsed/Refractory Multiple Myeloma (MM) (Paul
abstract #3963)
Richardson, Dana-Farber Cancer Institute, Boston, MA,
·A Phase I/II Study of Pomalidomide-Cyclophosphamide-
USA, abstract #302)
Prednisone (PCP) in Patients with Multiple Myeloma
·A Phase 2 Study of Elotuzumab in Combination with
Relapsed/Refractory to Lenalidomide (Antonio Palumbo,
Lenalidomide and Low-Dose Dexamethasone in Patients
University of Torino, Torino, Italy, abstract #632)
with Relapsed/Refractory Multiple Myeloma (Sagar
·Randomized, Open Label Phase 1/2 Study of Pomalido-
Lonial, Winship Cancer Institute, Emory University
mide (POM) Alone or in Combination with Low-Dose
School of Medicine, Atlanta, GA, USA, abstract #303)
Dexamethasone (LoDex) in Patients (Pts) with Relapsed
·Elotuzumab in Combination with Lenalidomide and
and Refractory Multiple Myeloma Who Have Received
Low-Dose Dexamethasone in High-Risk and/or Stage 2-3
Prior Treatment That Includes Lenalidomide (LEN) and
Relapsed and/or Refractory Multiple Myeloma: A Retro-
Bortezomib (BORT): Phase 2 Results (Paul Richard-
spective Subset Analysis of the Phase 2 Study (Sundar
son, Dana-Farber Cancer Institute, Boston, MA, USA,
Jagannath, Mount Sinai Hospital, New York, NY, USA,
abstract #634)
abstract #3968)
·ClaPD (Clarithromycin/[Biaxin®], Pomalidomide, Dexa-
·Combination of Bendamustine, Lenalidomide, and
methasone) Therapy in Relapsed or Refractory Multiple
Dexamethasone (BLD) in Patients with Refractory or
Myeloma (Tomer Mark, Weill Cornell Medical College,
Relapsed Multiple Myeloma Is Safe and Highly Effective:
New York, NY, USA, abstract #635)
Results of Phase I/II Open-Label, Dose Escalation Study
·High Response Rates to Pomalidomide and Dexametha-
(Suzanne Lentzsch, University of Pittsburgh, PA, USA,
sone in Patients with Refractory Myeloma, Final Analysis
abstract #304)
9
·Bortezomib-Bendamustine-Dexamethasone in Patients
Multiple Myeloma: PANORAMA 1 (Jesús San Miguel,
with Relapsed/Refractory Multiple Myeloma (MM)
University Hospital, Salamanca, Spain, abstract #3976)
Shows Marked Efficacy and Is Well Tolerated, but Assess-
This overview of the year's ASH highlights also serves as
ment of PNP Symptoms Shows Significant Discrepancies
an introduction to the forthcoming International Myeloma
Between Patients and Physicians (Heinz Ludwig, Univer-
Working Group (IMWG) publications, which will update
sity Hospital Vienna, Vienna, Austria, abstract #2928)
older guidelines and provide new ones in line with the
·A Phase 1 Study of Bendamustine and Melphalan Condi-
newly presented data. Among the new guidelines will be:
tioning for Autologous Stem Cell Transplant in Multiple
Myeloma (Tomer Mark, Weill Cornell Medical College,
·Dimopoulos and Terpos's update on imaging
New York, NY, USA, abstract #2042)
·San Miguel's analysis of the best of the new drugs, with
·BT062, An Antibody-Drug Conjugate Directed Against
reference to their mechanisms of action
CD138, Shows Clinical Activity in Patients with Relapsed
·Treatment of patients older than 75 years of age, piloted
or Relapsed/Refractory Multiple Myeloma (Sundar Jag-
by Palumbo
annath, Mount Sinai Hospital, New York, NY, USA,
abstract #305)
·GEP and High-Risk myeloma, by Chng and Munshi
·Vantage 088: Vorinostat in Combination with Bort-
·Risk stratification, by Chng, Durie, Lonial, and
ezomib in Patients with Relapsed/Refractory Multiple
Chanan-Khan
Myeloma: Results of a Global, Randomized Phase 3 Trial
·High-risk SMM and diagnostic testing, by Lonial, Kumar,
(Meletios Dimopoulos, University of Athens, Athens,
and Rajkumar
Greece, abstract #811)
·Secondary Primary Malignancies, by Durie and Crowley
·Vantage 095: Vorinostat in Combination with Bortezo-
·Balloon kyphoplasty and bone health, by Malloy,
mib in Salvage Multiple Myeloma Patients: Final Study
Kyriakou, and Durie
Results of a Global Phase 2b Trial (David Siegel, Hack-
ensack University Medical Center, Hackensack, NJ, USA,
·ISS and high-dose therapy, by Moreau, Crowley, and
abstract #480)
Durie
·Phase II Study of the Pan-Deacetylase Inhibitor Panobi-
·Role of supportive care agents, by Chanan-Kahn.
nostat in Combination with Bortezomib and Dexameth-
We thus anticipate a year of outstanding contributions to
asone in Relapsed and Bortezomib-Refractory Multiple
the guidelines for better understanding and management of
Myeloma (PANORAMA 2) (Paul Richardson, Dana-Farber
myeloma, and a year that will bring two new agents to the
Cancer Institute, Boston, MA, USA, abstract #814)
armamentarium of approved drugs to fight it.
·Update on a Phase III Study of Panobinostat with Bort-
ezomib and Dexamethasone in Patients with Relapsed
10
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