InternatIonal MyeloMa FoundatIon
ASCO 2008
Highlights
for Patients
Compiled by Lynne Lederman, PhD
This publication is sponsored by unrestricted educational grants from Celgene Corporation and Millennium: The Takeda Oncology Company.
ASCO 2008 Highlights for Patients
News from the 2008 ASCO Meeting
Side effects. Therapies that include thal and lenalidomide (len)
have a higher risk of causing blood clots in large veins (deep vein
New and updated data on novel and conventional therapies for
thrombosis) than other therapies. All combination therapies except
patients with newly diagnosed or relapsed/refractory multiple
len/dex carry the risk of nerve damage (neuropathy).
myeloma were presented at the 2008 meeting of the American Soci-
ety of Clinical Oncology (ASCO), May 30 through June 3, in Chicago,
Patients with kidney (renal) failure. Dr. Rajkumar pointed out
Illinois. Presentations included reports of data from clinical trials of
that lenalidomide leaves the body through the kidneys, so it may
novel agents in combination therapy, discussions of the role of stem
not be the best choice for patients with kidney (renal) failure. Two
cell transplantation (SCT), including the effects of novel agents on
clinical studies looked at the effects of therapies containing either
stem cell collection, and continued research into how best to deter-
lenalidomide or bortezomib in patients with kidney failure (renal
mine risk factors and to personalize therapy in an age of increasing
insufficiency) who had relapsed/refractory myeloma. These studies
use of gene expression profiling (GEP) and other techniques. This
are discussed in the section on relapsed/refractory myeloma.
year's educational session covered controversies surrounding the
How to choose a treatment. To assist in the choice of treatment,
initial treatment of multiple myeloma, timing of high-dose therapy
Dr. Rajkumar suggested considering the route of administration (by
in myeloma, and risk-adapted therapy of myeloma.
mouth or through a vein) and the patient's risk for dangerous clot
Newly Diagnosed Myeloma
formation (DVT). Both MPT and VMP can cause neuropathy; how-
ever, both of these combinations can be used in patients with kidney
Issues affecting the initial treatment of multiple
failure. VMP has no DVT risk but is given intravenously. The use of
myeloma
MPT requires that patients take some medication to prevent clots
In the educational session, S. Vincent Rajkumar, Mayo Clinic, Roch-
(DVT prophylaxis). Results of trials have shown that the combina-
ester, encouraged physicians to consider the patient as a whole, and
tion of lenalidomide with low-dose dex is effective. These results
to take into account supportive care, quality of life, the side effects of
should apply to the use of low-dose dex in other combinations. Dr.
therapy, and the disease itself. The choice of initial therapy should be
Rajkumar suggested that high-dose (HD) dex may be appropriate
guided by whether or not a patient is a candidate for transplant.
for patients with relapsed/refractory disease. Trial results for patients
with relapsed/refractory disease are discussed below.
Patients who are not transplant candidates. Dr. Rajkumar
believes that lenalidomide (Revlimid®) plus lower-dose dexametha-
Goals of therapy. Dr. Rajkumar believes that the goal of treatment
sone (Rd), bortezomib (Velcade®, btz) plus dexamethasone (dex),
should be complete response (CR). CR may predict a better long-
other bortezomib-containing regimens, e.g., bortezomib with tha-
term outcome. However, he cautions that patients should not be
lidomide (Thalomid®, thal) plus dex (VTD), may offer equal or
harmed by receiving more drugs just to achieve CR. The response
better response rates and fewer side effects than thalidomide plus
rate is important, but so is overal survival.
dexamethasone (thal/dex). He noted that thal/dex provides conve-
Duration of therapy. According to Dr. Rajkumar, controlled clinical
nient oral (by mouth) dosing, whereas bortezomib, which must be
trials should be used to decide which treatments can be given easily
administered through a vein (intravenously), may not be an option
on a long-term basis with the fewest side effects. There is a limit to
for patients in remote areas who can't travel to receive treatment.
how long some treatments can be given. Len with low-dose dex (Rd)
Patients who are transplant candidates. Combinations such
lends itself to long-term treatment. Btz/dex and thal/dex should be
as bortezomib, cyclophosphamide (Cytoxan®), and dex have high
limited to induction therapy before transplantation or until a maxi-
response rates yet do not interfere with stem cel col ection. Dr.
mum response is reached.
Rajkumar believes that high-dose dex as a single agent and the
Trial results
combination therapy VAD (vincristine/doxorubicin [Adriamycin]/
dexamethasone) should not be used any more. Dr. Rajkumar
lenalidomide with high- or low-dose dex
believes the options are changing for patients who are not candi-
Dr. Rajkumar presented data from the study entitled "Randomized
dates for transplantation. Until recently, MP (melphalan plus predni-
trial of lenalidomide plus high-dose dexamethasone versus lenali-
sone) has been the standard of care for this group of patients. MPT
domide plus low-dose dexamethasone in newly diagnosed myeloma
(MP plus thal) is better than MP or MEL100 (a lower than standard
(ECOG E4A03), a trial coordinated by the Eastern Cooperative Oncol-
dose of melphalan), according to the French myeloma group study.
ogy Group: Analysis of response, survival, and outcome with primary
The recently reported VISTA trial showed that btz plus MP (VMP) is
therapy and with stem cell transplantation." (abstract 8504) This
also better than MP.
study looked at data from the trial in newly diagnosed myeloma
3
in which patients received lenalidomide plus high-dose (HD) dex-
that there are trial data that both support and fail to support this regi-
amethasone (RD) or len plus low-dose dexamethasone (Rd). After 4
men. Younger patients and those with better kidney function may
months of therapy, patients could stop therapy and receive a stem
benefit more, and more recently diagnosed patients appear to have
cell transplant (SCT) or continue to receive the trial therapy. The
a higher 10-year survival rate because of the introduction of novel
results show that len/dex is effective in newly diagnosed myeloma
therapies (bortezomib, lenalidomide, and thalidomide). Dr. Fermand
regardless of the patient age or transplant eligibility. The survival
does not think there are sufficient trial results to support the risk and
rate at 2 years for patients who received continuing Rd was similar
cost of performing two transplants rather than one, and states that
to the rate for patients who received SCT after either RD or Rd for
further study is needed. Other studies that Dr. Fermand suggested
4 months.
that are still needed include adding btz to HDT with MP, confirming
Dr. Rajkumar suggested that the most important question patients
high-risk factors previously associated with poor outcome now that
face today in the era of new drugs is whether they still need a trans-
newer agents like btz, len, and thal are available, and determining
plant. This is something that can be tested in the future. Madhav V.
the role of thal for maintenance therapy.
Dhodapkar, Yale University, discussed this presentation and pointed
Two studies looked at various combination therapies and regimens
out that this trial was designed to determine response rate and side
prior to and after SCT in newly diagnosed patients.
effects, not survival, and most patients received treatment for a short
Jean-Luc Harousseau, CHU Hôtel-Dieu, Nantes, presented "Bort-
period of time. He found the study interesting because although Rd
ezomib/dexamethasone versus VAD as induction prior to autologous
has a better survival rate, the response rate is lower. However, side
stem cell transplantation (ASCT) in previously untreated multiple
effects are also lower with Rd than RD, which could allow patients to
myeloma (MM): Updated data from IFM 2005/01 trial." (abstract
take Rd for a longer period of time. Dr. Dhodapkar agreed that the
8505) This phase 3 study compared induction therapy of btz/dex
effect of Rd on survival with and without early SCT needs to be tested
with VAD in patients who were younger than age 65 years. The
in a trial specifically designed to address this issue, which will require
study also evaluated consolidation therapy with two cycles of dex,
a longer fol ow-up.
cyclophosphamide, etoposide, and platinum (DCEP). All patients
Bortezomib-based therapy
received MEL200 (high-dose melphalan) followed by SCT. Patients
Craig B. Reeder, Mayo Clinic, Scottsdale, presented "Efficacy of induc-
could receive a second transplant if they did not have at least a
tion with CyBorD in newly diagnosed multiple myeloma." (abstract
very good partial response (VGPR) after the first SCT. Btz/dex was
8517) This phase 2 study in patients with newly diagnosed myeloma
superior to VAD for al stages of myeloma and for high-risk disease.
tested the combination of cyclophosphamide, bortezomib, dexam-
The study is in an early stage of follow-up and hasn't yet shown an
ethasone (CyBorD) prior to SCT. Response rates were good. Serious
improvement in overall survival and disease-free survival in patients
side effects included abnormally reduced numbers of red and white
as a whole. More patients in the btz/dex arm needed a second stem
blood cel s and platelets, abnormal y high blood sugar, diarrhea,
cel col ection. A study of btz/dex vs. btz/dex plus thal has just started.
abnormally low potassium in the blood, neuropathy, and abnormal
Suzanne Trudel, Princess Margaret Hospital, Toronto, who discussed
clotting. A new group of patients was enrolled after the dose of btz
the presentation, agreed that failure to demonstrate improvement in
was changed from twice weekly to once weekly, and the dex dose
outcome may reflect the need for longer follow-up, although com-
was lowered after the first 2 cycles. CyBorD will also be studied in
plete response (CR) may not be the best predictor of survival for
a trial comparing it with lenalidomide/bortezomib/dexamethasone
patients who do not have high-risk disease. Also, it may be difficult to
(RVD) and with RVD plus cyclophosphamide.
demonstrate improvement in survival in the era of effective salvage
therapies. She didn't think that btz/dex should be considered the
regimen with both lenalidomide and bortezomib
standard induction treatment prior to SCT at this time. To become
Paul G. Richardson, Dana-Farber Cancer Institute, Boston, discussed
the standard of care, a clinically meaningful endpoint should be
"Safety and efficacy of lenalidomide (Len), bortezomib (Bz), and dex-
shown, e.g., improved quality of life, difference in cost-effectiveness,
amethasone (Dex) in patients (pts) with newly diagnosed multiple
and/or decrease in number of patients needing a second transplant.
myeloma (MM): A phase I/II study." (abstract 8520) This is an early-
She noted also that second transplant is not the standard of care in
phase trial to define the maximum doses of len/btz/dex that can be
the US and many other countries. Finally, an improvement in overall
tolerated, as well as the response rates, in patients who can receive
survival and disease-free survival wil be required to see an effect of
SCT. The results of the Rd vs. RD trial led to the inclusion in this study
this regimen on patient care.
of an additional dose level of len/btz/dex with reduced dex. The fol-
low-up time is short, but response rates were good and the side effects
Antonio P. Palumbo, University of Torino, presented "Bortezomib,
were as expected. The combination of len/btz/dex is being tested in
pegylated-liposomal-doxorubicin and dexamethasone (PAD) as
other studies.
induction therapy prior to reduced-intensity autologous stem cell
transplant (ASCT) followed by lenalidomide and prednisone (LP)
Stem cell transplantation
as consolidation and lenalidomide alone as maintenance." (abstract
In the educational session, Jean-Paul Fermand, Hôpital Saint-Louis,
8518) This study looked at PAD (btz, PLD, dex) compared with btz/
Paris, called HD therapy and SCT (HDT) the standard of care, noting
dex induction therapy prior to SCT. Len plus prednisone (LP) was
4
used for consolidation therapy, then single-agent len was tested as
studied to see if len affects the number of collections required or the
maintenance therapy. The study included patients aged 65 to 75 years
number of stem cells collected.
as well as younger patients who couldn't tolerate MEL200. This study
Ruben Niesvizky, Weill-Cornell Medical College and New York Pres-
used MEL100 with PAD. Responses, projected event-free survival,
byterian Hospital, New York, presented "Bortezomib, cyclophosph-
and overall survival were good. He suggested that age 70 years might
amide, and filgrastim leads to high-yield CD34+ stem cell collections
be the upper limit for PAD-MEL100, although longer follow-up times
in multiple myeloma." (abstract 8587) In this study patients received
are needed to determine this. LP increased the response rate after
btz/dex with or without PLD. The study is ongoing, and all patients
SCT, possibly because len is a new drug for the patients in this study.
who have undergone stem cell collection have had adequate num-
Dr. Palumbo also suggested that reducing the frequency of adminis-
bers of cel s col ected.
tration of btz to weekly may reduce the incidence of neuro pathy, and
concluded that this sequential regimen may become a new strategy,
Relapsed or Relapsed/Refractory
especially for patients who cannot tolerate full-dose SCT.
Myeloma
effects of lenalidomide and bortezomib on stem cell collection
The results of several studies in patients with relapsed or relapsed/
Some prior studies showed a decrease in stem cell numbers, a
refractory multiple myeloma were presented.
decrease in the average daily collection of stem cells, an increase in
the number of collections required, and/or failure to collect sufficient
Lenalidomide-based therapies
stem cells for even one transplant after treatment with lenalidomide.
Mohamad. A. Hussein, formerly of the Cleveland Clinic, Weston, and
Two poster presentations addressed this issue, and one examined
Moffitt Cancer Center, Tampa, presented "Final analysis of MM-014:
the effect of bortezomib on stem cell collection.
Single-agent lenalidomide in patients with relapsed and refractory
multiple myeloma." (abstract 8524) This was the final analysis of a
Harshita Paripati, Mayo Clinic, Scottsdale, presented "Impact of
study of the effectiveness and safety of lenalidomide as a single agent
lenalidomide therapy on stem cel mobilization in myeloma."
for patients with relapsed/refractory myeloma. The overall response
(abstract 8543) Nearly half the patients who received len-based
rate was 44%, and the duration of response was 13 months. Median
induction therapy experienced a failure to collect stem cells, which
overall survival was nearly 2 years, and over a third of the patients
was a significantly greater percentage of patients than that for those
were able to receive HD therapy and SCT. The most common seri-
who received other induction therapies. However, re-collection and
ous side effects included abnormal y low numbers of white blood
combination with the first collection gave the majority of len-treated
cells, platelets, and red blood cells, which were managed with dose
patients sufficient cel s for at least one transplant. In this study, G-CSF
reduction or interruption of therapy and growth factors. Dr. Hussein
(granulocyte colony-stimulating factor) was used to col ect stem cel s.
concluded that len monotherapy resulted in meaningful long-term
Dr. Paripati suggested that other strategies for collecting stem cells
benefit for patients with relapsed or refractory myeloma, and had a
following lenalidomide induction, such as using cyclophosphamide
manageable safety profile.
or a new drug, AMD 3100 (plerixafor), which is not yet approved,
along with G-CSF, may be considered in patients treated with lenali-
Paul Richardson presented "Long-term responses observed with
domide. A lenalidomide "holiday" prior to stem cel col ection may
lenalidomide therapy for patients with relapsed or refractory multiple
also be considered. Limiting the number of monthly cycles of lenali-
myeloma." (abstract 8525) This was a long-term follow-up of patients
domide prior to mobilization may also help.
remaining on therapy in an early study (MM-007) that formed the basis
of the phase 3 MM-009 and MM-010 studies. Although disease-free
Rachel I. Cook, University of Pennsylvania Abramson Cancer Center,
survival was short, overall survival was "impressive." This follow-up
Philadelphia, discussed "Lenalidomide and stem cel col ection in
was not originally planned. Dr. Richardson concluded that because
patients with multiple myeloma." (abstract 8547) This study com-
a subset of patients responding to len with or without dex could
pared collecting stem cells using G-CSF alone with collections using
remain on treatment for at least 4.1 years, len can be considered an
G-CSF/cyclophosphamide (cy), and focuses on whether initial treat-
effective, durable, and well-tolerated therapy for heavily pretreated
ment contained a len/dex-based regimen or not. In this study, where
patients with relapsed/refractory myeloma. This long-term therapy
side effect results were not available and some of the groups being
requires close observation for side effects. Dose adjustments where
compared were small, the number of cycles of len/dex did not seem
needed may allow patients to tolerate the treatment for long periods
to be related to the number of stem cell collections required or the
of time, which may al ow them to maintain a long-term response.
number of stem cells collected. The number of stem cells collected
Dr. Richardson also suggested that the role of len in maintenance
was lower for patients who had taken lenalidomide compared with
therapy may be important.
those patients on non-lenalidomide containing regimens, but the
difference was not clinically significant. Patients who received G-CSF
Effect of therapy on kidney function
were more likely to have a failure to collect compared with those
Donna M. Weber presented a poster on "The efficacy and safety of
receiving G-CSF/cy, regardless of the induction regimen. Dr. Donna
lenalidomide plus dexamethasone in relapsed or refractory multiple
M. Weber, MD Anderson Cancer Center, Houston, who discussed this
myeloma patients with impaired renal function." (abstract 8542)
presentation, suggested that larger numbers of patients need to be
5
This study looked at some of the patients in the recent phase 3 trials
of which confers a different prognosis. He emphasized that it is no
of len/dex compared with dex (MM-009 and MM-010). This part of
longer acceptable to think of myeloma as a single disease entity, nor
the study looked focused on patients who received len/dex. These
as a stable disease, because multiple changes in myeloma tumor cells
patients were divided into groups that reflected the degree of kid-
occur over time. Although patients can be classified as having high-
ney failure (renal impairment) defined by the results of a laboratory
or standard-risk disease, some therapies may work as well in patients
test called creatinine clearance (CLCr). Creatinine, a waste product
with either high- or standard-risk profiles. An example of this is
from protein in the diet, appears in the blood and is removed by the
bortezomib, which, as part of VMP, overcomes the high risk associ-
kidneys. Creatinine clearance is a measure of the rate at which crea-
ated with certain rearrangements of chromosomes (translocations,
tinine is removed, and reflects the health of the kidneys. The groups
the exchange of material between two different chromosomes) or
included patients with no renal impairment and with mild, moder-
deletions of parts of chromosomes. Dr. Stewart believes that patients
ate, or severe renal impairment. The patients with greater degrees of
with high-risk disease deserve to have their own clinical trials.
kidney failure were more likely to need the dose of their medication
Ariel Anguiano, Duke University, Durham, discussed "Gene expres-
reduced. These patients were also more likely to have lower levels
sion profiles defining molecular subtypes, coupled with signatures
of platelets, the component in the blood that allows it to clot to
of tumor biology and chemotherapy sensitivity, provide a novel
prevent bleeding. Dr. Weber suggested that platelet counts should
therapeutic approach to multiple myeloma." (abstract 8501) This
be checked carefully in patients with kidney failure who are taking l
study examined patterns associated with good and poor outcomes
en/dex. The combination of len/dex improved kidney function in
based on gene expression profiling (GEP). These patterns represent
68% of patients with kidney failure by at least one level; for exam-
abnormal functioning of cancer genes, abnormal numbers of chro-
ple, from severe to moderate, or moderate to mild. Nearly half of
mosomes, or alterations of chromosomes, such as translocations. He
all patients who had some degree of kidney failure at the beginning
presented 7 different subtypes that have been seen in patients with
of the study improved to the point that they could be classified as
myeloma, each of which confers a different survival rate. Several of
having no renal impairment by the end of the study. Lenalidomide is
these subtypes confer a higher risk of disease progression and death,
generally effective in patients regardless of the degree of kidney fail-
which points out the need for new therapies. Dr. Anguiano looked
ure. Dr. Weber said, however, that further trials are needed to define
at markers for altered cancer gene activity, altered myeloma cell
the effectiveness and safety of lenalidomide plus dexamethasone in
environment, and sensitivity to chemotherapy within these subtypes
patients with renal impairment.
in several different groups of patients. He showed that each of the
Joan Bladé, Hospital Clinic, Barcelona, presented a poster entitled
subtypes has its own distinct pattern of myeloma cel biology and
"Effect of pegylated liposomal doxorubicin (PLD) plus bortezomib in
sensitivity to chemotherapy. Dr. Anguiano concluded that patterns
multiple myeloma patients with renal insufficiency." (abstract 8562)
of cancer gene alterations and altered tumor environments may fur-
This was a study of patients with relapsed/refractory myeloma who
ther define subtypes of multiple myeloma. Looking at these subtypes
were in the phase 3 trial comparing pegylated liposomal doxorubicin
may reveal information about the biology of disease progression and
(Doxil®, PLD) plus bortezomib with bortezomib (btz) alone (DOX
treatment, allow selection of better therapy targets, and may help
IL-MMY-3001). An abnormal creatinine clearance rate was used to
guide therapy in multiple myeloma in the future. This presentation
define abnormal kidney function. Patients receiving the combination
was discussed by Wee J. Chng, National University Hospital, Singa-
therapy had a significantly longer disease-free interval and better
pore, who said that further studies and confirmation using other
responses than patients who received btz alone regardless of kidney
methods will be needed before these strategies can be used to guide
function. Patients with kidney failure who received either treatment
treatment.
had improved kidney function. Anemia (abnormal y low numbers of
Bart Barlogie, University of Arkansas for Medical Sciences, Little
red blood cells) and diarrhea occurred more often in patients with
Rock, presented "Total therapy (TT) for myeloma (MM) ­ 10% cure
kidney failure, but hand and foot syndrome, which is associated with
rate with TT1 suggested by >10yr continuous complete remission
PLD, occurred less often in this group.
(CCR): Bortezomib in TT3 overcomes poor-risk associated with
Risk-Adapted and Individualized
T(4;14) and DelTP53 in TT2." (abstract 8516) In this presentation, he
Approaches to Therapy
reviewed the history of total therapy (TT) treatments, which include
TT1, TT2 with or without thal, and TT3 with btz and thal. All of these
Several studies looked at how to better define risk factors,
treatments were developed with the idea of using all possible agents
the goal being to select the best therapy for each individual patient.
effective against myeloma to reduce the tumor burden maximally up
Risk-adapted therapy of multiple myeloma
front, rather than waiting for relapse to use second- and third-line
agents. Since 1989, 1200 patients have been enrolled in successive
Keith A. Stewart, Mayo Clinic, Scottsdale, discussed the need to con-
TT protocols, with steady improvement in outcomes moving from
sider unique features of individual patients to tailor therapy in prac-
TT1 to TT2 to TT3. GEP can be used to define low-risk myeloma in
tice, rather than just using these features to estimate prognosis. He
85% of patients. For these patients, TT3 gives better outcomes than
reviewed the high genetic variability of myeloma, describing at least
TT2. However, in the 15% of patients defined as having high-risk
9 genetic events associated with the development of myeloma, each
6
disease, despite high CR rates, TT3 and TT2 have similar poor out-
used as a predictor of long-term survival. He noted that the popula-
comes. Dr. Barlogie was surprised to see that among these high-risk
tion of patients with primary resistant myeloma is disappearing with
patients, the best survival is in patients treated with TT2, resulting
the advent of novel therapies. The results suggested that patients
in CR sustained for 3 years or longer. However, if CR is lost within 3
with primary resistant myeloma have a more urgent need for SCT.
years, the outcome is poor, and is worse than for those who never
For primary therapy alone with no SCT, patients whose disease was
had CR in the first 3 years. For patients treated with TT3, the risk of
in CR survived significantly longer than those with partial response
relapse declines more rapidly in high-risk than in low-risk myeloma.
(PR) or no response (NR). For patients with PR after primary therapy,
If patients with high- risk disease survive 3 years, then their chance of
those who convert to CR after SCT have significantly longer survival
survival will be more like that of patients with low-risk disease.
than those who remain in PR. There are four pathways to CR: pri-
Dr. Barlogie is looking toward development and use of TT4 and TT5.
mary therapy alone CR, CR after primary therapy plus CR after SCT,
For patients with low-risk myeloma, it is difficult to improve upon
PR to primary therapy then CR after SCT, and NR after primary ther-
TT3; for these patients, TT4 is designed to reduce side effects. In a
apy then CR after SCT. CR is generally associated with longer survival
planned trial, patients will be separated by risk based on GEP, and
time, and the longer patients remain in CR, the longer they survive.
wil receive TT3 or TT3-lite (one induction, one consolidation, pulsed
CR vs. NR, PR vs. NR, stage I vs. stages II or III, and HD therapy vs. no
melphalan). For patients with high-risk disease, the goal is to sustain
HD therapy are all associated with longer survival. CR is the stron-
CR with a dose-dense but less dose-intense therapy (TT5). TT5 is
gest indicator for longest time of survival and represents the major
based on MEL80-VTD-PACE, that is, 8 drugs in lower doses, fol owed
marker for long-term survival. CR, however achieved, was associated
by alternating R-VD or M-VD as maintenance therapy to avoid bone
with longer survival than other response outcomes. SCT for patients
marrow side effects. Dr. Barlogie believes that duration of CR rather
with CR to primary therapy did not further prolong survival.
than CR rate is the best predictor of survival, although the most diffi-
In his discussion of Dr. Wang's presentation, Dr. Rajkumar said it
cult one to measure because of the time needed for observation. He
showed that CR is an excel ent measure of outcome. He cautioned
concludes that cure is a realistic outcome in myeloma, with greater
that even the best regimens available now give CR rates of only 30%
than 10 years of sustained CR for patients receiving TT1, although
to 40%, yet a lot of patients who don't have CR can have a long sur-
this may be shorter for TT2. Late relapse in some patients shouldn't
vival. Therefore, it is important to see how these patients can be
be an argument against curability, he says, because this happens in
identified. For any regimen, even if it is ineffective, there will be
all cancers, including childhood leukemia. Bortezomib has changed
responders who do better than non-responders. Although CR is
the outlook for some myeloma subgroups that have poor outcome
desirable, is predictive, and is needed for a cure, the way it is cur-
with other therapies. Kenneth C. Anderson discussed this presenta-
rently defined, CR does not indicate a cure. This is because, as Dr.
tion. He called it a landmark presentation, and agreed that the con-
Rajkumar pointed out in the educational session, the definition of
cept of talking about the cure of myeloma is here. The new studies
CR is not precise. CR may be a good predictor of overall survival in
mentioned will ask whether high-dose therapy is needed for patients
many but not all trials. Dr. Barlogie has made the point that myeloma
with low-risk disease when bortezomib is part of the therapy.
is often preceded by monoclonal gammopathy of undetermined sig-
Hervé Avet-Loiseau, Institute de Biologie, Nantes, discussed
nificance (MGUS), which is present in 3% of the US population. This
"Use of high-density SNP-array analysis to identify novel chromo-
represents 10 million people who are doing well. That suggests that
somal abnormalities that predict survival in multiple myeloma."
a subset of patients with myeloma don't need to be in CR; they could
(abstract 8522) This study looked at DNA from plasma cells from
be in VGPR (very good partial response) and still do quite well. They
newly diagnosed patients younger than age 65 years who received
won't benefit from reducing their myeloma protein to zero, and may
HD melphalan. The DNA was tested for abnormalities in chromo-
actual y be harmed by it.
somes and an analysis was done to determine how these related
Lynne Lederman, PhD, is a medical writer based in Mamaroneck,
to survival. New chromosomal abnormalities were identified.
New York.
Good outcome was associated with some of these abnormalities,
poor outcome with others. Dr. Avet-Loiseau concluded that use of
gene expression arrays should enhance the understanding of how
myeloma develops and ultimately lead to an individualized thera-
peutic approach.
Michael Wang, MD Anderson Cancer Center, Houston, presented
"Complete remission and survival in multiple myeloma." (abstract
8523) This study looked at the outcomes among newly diagnosed
patients age 65 years or younger who received primary chemotherapy
(dexamethasone-based induction therapies) followed by intensive
therapy (HD-melphalan-based intensive therapy supported by SCT)
within the first year. Dr. Wang was interested in seeing if CR could be
7
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Telephone:
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