May 2011 Archives
returned to California and wanted to offer a few final thoughts from the
International Myeloma Workshop concluded May 6, 2011. If you're a patient or
caregiver who really stays current on MM developments, you might say there was
not much new presented at this conference beyond the ASH conference five months
ago. The notable exceptions were:
maintenance showing an Overall Survival benefit after two years; and
cancers studies of several Revlimid maintenance trials appear to add 3 to 4% to
normal risk for patients getting another cancer. This 3 to 4% number seems similar to the potential of ONJ
resulting from Aredia/Zometa treatments.
In my humble opinion, the benefits of both outweigh the risks, but as
patients we need to pay attention to potential side effects.
of these conclusions also need longer study times in order to confirm results.
new drugs, Carfilzomib and Pomalidomide continue to lead the pack in terms of
safety and efficacy results from clinical trials as they progress toward FDA
application for approval. But
there are many other drugs such as HDAC Inhibitors (e.g. Vorinostat,
Panobinostat), Monoclonal Antibodies (e.g. Elotuzumab, CNTO328), and AKT
Pathway Inhibitors (e.g. Perifosine) showing successful trial results and
synergies with current treatment.
also appreciate that safety factors, both hematological and non-hematological,
are carefully measured in these trials along with response levels for different
risk groups as well as patients relapsed/refractory to different drugs.
these conferences always reconfirm the complexity of MM as it's currently
understood. When MM experts
disagree on "best" treatments, I wonder how we patients can possibly make best
then I remember that our goal is to manage our disease for as long as possible,
and if a particular treatment doesn't work or stops working, we need to be
ready to try another treatment.
second and third opinions for MM experts can be very valuable. However, we're the ones who need to be
our own best advocates and should take advantage of the many excellent MM
publications, teleconferences and on-line presentations available.
on the IMF website, for example, you can already check out summary remarks and
some of the actual presentations made by MM experts at the IMW workshop. You can also view the archived webcast of the IMF Journalists Workshop, which was live-streamed during the meeting in Paris, for a great overview of the event.
wishes for all of our good health.
4 wrapped up at the International Myeloma Workshop with the following topics: 1) supportive care; 2) diagnostic criteria for treatment and retreatment; and 3) a catch-all of some additional abstracts.
to 90% of MM patients 60 and older experience anemia. While blood transfusions are only temporary, something like
Epogen infusions are recommended if your hemoglobin is below 10. (Yet in some
cases, a patient needs to be on therapy in order to be reimbursed.)
vein thrombosis (DVT) prophylaxis (e.g. Warfarin or daily aspirin) is
certainly recommended for IMIDs treatment, but other
DVT risks include catheter or pacemaker placement, surgery such as kyphoplasty,
and prolonged immobilization. The latter could happen on a long flight home...hmmm, I'd
better remember that!
disease and vaccinations were other topics of discussion but nothing surprising
(e.g. no live viruses for MM patients, which we've known for a while).
"The Diagnostic Criteria" was a presentation for oncologists to make certain they do
all the correct tests to verify MM.
For example, just because a person might have renal failure or bone
disease does not mean that they have MM.
And when to treat (symptomatic MM) and re-treat (clinical or protein
relapse) is standard.
trials were updated showing the benefits of Velcade consolidation after a stem cell transplant; Pomalidomide dosage tests (I suspect they'll go to FDA with 4mg but 2mg may
also work); and Carfilzomib continued good results. What's particularly appealing about Pomalidomide and
Carfilzomib are the lower toxicity levels compared with their predecessors
(e.g. minimal peripheral neuropathy).
there was an interesting presentation on MM mortality rates, which have been
declining (-2.3% annually) for the younger set (<65 yo) since 1995 due to
transplants, as well as for the older set (-1.8% annually) since 2002 due to
That's certainly the
right direction for all of us!
The International Myeloma Workshop in Paris ended with an IMF Patient/Family seminar. Since most of it was in French, I
didn't understand a lot. Yet I
was able to determine that French MM patients and caregivers have many of the same
concerns we have in the U.S. They also wonder where to find MM oncologists. Fortunately, this country has a number
of MM experts.
suspect when I get home in a few days I'll put up one last post
on this blog summarizing my final thoughts. I'll also check out some of the poster announcements while
on the plane, and incorporate any new information that I haven't already
me know if you've got any questions about the workshop and I'll do my best to
answer them, or point you in the right direction.
Additional news from Day 3 of the International Myeloma Workshop in Paris:
always appreciate listening to Dr
S. V. Rajkumar from the Mayo Clinic. He talked about his practice of putting patients into one of three categories: High risk (about 15%); intermediate risk (10%); and
standard risk (75%). This allows him to treat each group differently. (Check out www.msmart.org for specific details.)
Dr. Rajkumar does not
use Melphalan, Thalidomide, High-dose Dex, or Velcade twice/week; and he
definitely follows the recommended standard to NOT treat mgus or smoldering MM.
So what does he do? He treats patients in the standard-risk category with Revlimid and low-dose Dex. That practice drew immediate disagreement from another
MM expert. Many doctors believe that more treatment up front is better, and that patients should be getting at least a three-to-four drug cocktail, e.g RVd or VMPT.
your best bullet at the beginning of the disease," says Dr. A. Polumbo.
For patients who fall into the intermediate-risk category, Rajkumar believes in a Velcade regimen, because Velcade overcomes
translocation (4;14) and chromosome 13q deletion, part of Mayo's "intermediate"
definition. Velcade is
only given once a week and sub-q to minimize side effects.
Rajkumar says he really doesn't know the best treatment for those who fall into the high-risk category, given lack
of successful protocols for high-risk patients, but he probably does RVd.
Length of treatment is determined by category as well, says Rajkumar: 18
months for standard-risk patients, then "discuss" maintenance; one year for intermediate-risk patients, then Velcade
maintenance once every other week for two years; and for high-risk patients, do whatever is needed
to get into a CR, then Velcade until progression.
as precise as this may sound, Rajkumar also says: "If anyone says 'xyz is the
standard of care,' they are wrong. Rather, they can only offer their
And in fact, for the rest
of the session I listened to descriptions of alphabet soup trials using
VMP, VTD, RVD, MPR and more, many followed by maintenance treatments Rev, Vel,
Three of the International Myeloma Workshop arrived bright and early this spring
day in Paris.
schedule was filled with important discussions: Secondary Malignancies in
Myeloma; Optimizing Patient Outcomes; Newly Diagnosed Patients Over 65; and New
Drugs and Therapeutic Approaches.
no doubt, Revlimid maintenance was the Number One topic of interest because it
had previously shown success in extending EFS (Event Free Survival). And today, the IMF announced that a U.S.
trial using Revlimid following a stem cell transplant resulted in improved OS
(Overall Survival) of 90% at two years, compared to 83% at two years on the
when folks on the placebo switched to Revlimid maintenance, they also
experienced OS gains.
great news was tempered by a discussion of secondary cancers following
long-term maintenance with Revlimid that was first mentioned at ASH 2010 as
part of a French study.
large studies were analyzed for secondary cancers, and of course, one also
needs to remember that as we get older our chances for cancer also
increase. Some studies depicted
some tendency for Revlimid maintenance arms to show a few more secondary
cancers: 1) 8% (Revlimid) versus 2% (placebo) in the French study; 2) 8% versus
2% (U.S. study); 3) 6% versus 3% (Italian study). But in other studies, the
numbers were closer to being the same.
the end, when the panel was asked, "What does all this mean?"
I interpreted their responses to be: "There appears to be a small difference--and
we'll certainly know more in a year--but at this time it appears the benefit of
Revlimid maintenance far outweighs the risk."
still more drugs are in the pipeline, providing patients more options. Carfilzomib and Pomalidomide are farthest
along in Phase 3 trials. HDAC
inhibitors (e.g. Vorinostat, Panobinostat) don't seem to work alone, but appear
to be synergistic with Velcade and Revlimid. Monoclonal antibodies such as
Elotuzumab and Siltuximab are entering Phase 2 trials with Revlimid and Velcade
Dr. Kenneth Anderson said today: "When we meet again in two years for the IMW, I'm
hoping we can say that myeloma is a chronic illness with sustained CR's in a
significant number of patients."
I attended the IMF press conference, which was streamed live to the IMF website, and was designed to help put some of the new data in context. The webcast is archived on the site so that those who missed it can view it at their convenience.
last day of meetings begins at 7:45 a.m. In the afternoon, I'll be at the IMF
Day 2 of the International Myeloma
Presentations started at 7:45 a.m. Just imagine if you had been given the
8:15 p.m speaking slot more than 12 hours later!
The day's topics were: 1) treatment
for newly diagnosed < 65yo; 2) continuum of care; 3) high-risk entities; 4) whether or not to treat patients with smoldering MM; and 5) bone
Here were the discussions I found most interesting:
Transplants these days are being looked
at in phases of induction, harvest, SCT, consolidation and maintenance. And while "<65yo" was in the topic
heading, speakers recognize that physiological age is more important than
chronological, plus no co-morbidities and normal organ function (except a
transplant can be done for patients with compromised kidney function).
Many docs also recommend cytoxin before
harvest, with the goal of producing cleaner stem cells. If consolidation is done, it's
typically short term, say two months of Rev-Vel-dex before lower-dose Rev-dex
The role of CR (Complete Response) was
also discussed, with some saying the goal is to always get a CR (and this may
be even more important for high-risk patients). Dr. Bart Barlogie noted that duration of CR is more critical
and noted that many high-risk patients get into a CR but relapse quickly.
As much as we appreciate vacations from
treatment ("treatment holidays"), many MM experts believe that treatment should
be a continuum and that 2011 goals should be to extend survival rather than
symptom control. Others believe that prolonged therapy improves PFS
(Progression Free Survival) but we should construct clinical trials to determine
who benefits most by continuous therapy.
Dr. Ken Anderson noted that several new
drugs don't necessarily work on their own but offer a synergistic approach when
combined with current novel drugs, stressing again that combination therapies
are the future because MM cells seem to have so many
potential gateways for reproduction.
In addition, patients can acquire genomic mutations as a result of a
particular drug treatment, again stressing the need for combination therapies.
Trials are now in process to determine
if early treatment can delay the progression from Smoldering MM to full-blown
MM. It's hard to fathom the idea
of being treated when you have no symptoms (this is still the standard of care),
but it does appear that treating "high-risk" SMM does delay the onset of MM and
one would hope provides Overall Survival benefit.
Finally, the effectiveness of bone
scan techniques were reviewed. The
bone survey (x-rays) is least effective because there needs to be considerable
bone involvement (30%) for it to show up.
CT scan is more effective and easier on the patient but causes
significant more radiation exposure.
MRI (even over CT-PET scan) is preferred because it's non-invasive and
detects soft tissue disease resulting from bone disease as well as lesions.
Family Patient Seminar, Friday Afternoon
The sessions end here on Friday around
1 p.m., just in time for the folks from the IMF and local MM experts to conduct a
Family Patient Seminar in Paris Friday afternoon. I'm looking forward to attending as well and figure at least
I'll understand Dr. Brian Durie and
what's on the slides of other presenters.
I'm assuming everything else will be in French and it should be
fabulously informative for local patients and caregivers.
Well it's 2 a.m.
and I have a 6:15 a.m. wake-up call to get a good seat for the first presentation
at 7:45 a.m. But then again, I did
see the Eiffel Tower strobe lights twinkle at midnight, so all is ok.
Tuesday was Day 1--Opening Day for the International Myeloma Workshop. Presentations began at 10 am and ended
at 7:30 pm (the next 2 days begin at 7:45 am, so this was a "short" day).
I tell you that these meetings are being held at the Louvre? There are 2,000 MM researchers and
oncologists from 67 countries just a stone's throw from Mona Lisa.
presentations focused on myeloma genetics and cell biology, topics that are
typically over my head, and I know won't affect decisions we need to make today
or this year. That said, I'm glad
these topics are being investigated, and I usually end up with a few takeaways.
always told that myeloma is a very complex disease and that treatments work
differently for each of us because seemingly no two MM's and no two people are
alike. Today's presentation only
reaffirmed that. Researchers know
that MM needs to be further stratified and classified so that ultimately we
know which treatment is best for us. It may also make a difference in
establishing targeted clinical trials.
the moment, we know some differences among our fellow patients. Examples
include our stage--anything from MGUS to Smoldering, to Stages 1, 2, and 3. We probably know some folks are IgG or
IgA, kappa or lambda, some know they are "standard risk," some are "high risk."
where some of the difficulties begin.
Some researchers define "high risk" as factors determined by FISH and
cytogenetic tests, such as non-hyperdiploidy, chromosome deletions and
translocations. However, that seems very broad. Other classifications include
Gene Expression Profiling, SNP arrays and next-generation genomics sequencing
think one of the presenters summarized it best when he said, in so many words,
that "classifications today of MM appear to involve overlapping subsets rather
than distinct buckets."
disease was also discussed today.
For bisphosphonates, 50% of Aredia or Zometa ends up in the bone but 50%
gets flushed through the kidneys.
However, these have both been shown to reduce skeletal events by 50%,
and recently Zometa showed an anti-myeloma benefits of several months (probably
true for Aredia as well). ONJ
(osteonecrosis of the jaw) affects 3.5% of patients--something we need to be
aware of--but I still would (and did) take bisphosphonates when
are also studies indicating proteasome inhibitors like Velcade and IMIDS such
as Revlimid may also help reduce bone loss. However, when it was asked if patients therefore don't need
bisphosphonates, the MM experts agreed that patients diagnosed with bone
involvement should still start bisphosphonates early in their treatment.
in a prior blog I mentioned the IMF's International Myeloma Working Group
(IMWG). Near the end of tonight's
meeting, Susie Novis, IMF President, showed a 5-minute video about the IMWG.
It's a great video and if it isn't posted yet on the IMF website, it may very
well be there by the time you reach this, just as there are already a couple of
videos already posted from IMW.
Gotta get some sleep now
since it's a long day and early start to Day
Before the official conference starts on Tuesday, I sat in several Roundtable discussions Sunday
and Monday led by the IMF and consisting of 15 to 25 active participants at each
specialists, procedural specialists (e.g. orthopedic back
specialists), and representatives from companies talked about issues important
to myeloma patients.
roundtables were facilitated by Dr. Brian Durie with the objective of asking
and answering questions associated with a particular treatment or drug.
All the participants (including myself)
are under manufacturer's non-disclosure agreements and are not permitted to
discuss meeting details, but I can tell you that the vigorous discussions were
"spot-on" in reflecting patient concerns.
example, in the Medtronics meeting (kyphoplasty), I saw how experts are trying
to answer questions and update guidelines on kyphoplasty usage. For example:
1) How soon should
kyphoplasty be considered for back pain classified as severe versus significant
2) How does treatment and safety effectiveness of kyphoplasty
compare with vertebroplasty and non-surgical management of back pain?
are the best imaging techniques (bone survey, MRI, PET and CT scans) to determine
treatment decisions while considering insurance reimbursement?
meetings with Celgene (Pomalidomide, Revlidmid, Thalidomide) and Onyx
(Carfilzomib) reaffirmed good clinical trial results presented at ASH'10 last
December and plans for additional trials.
These trials are necessary to answer questions about drug efficacy and
safety profiles for usage in patient settings refractory/relapsed, first-line usage
and maintenance. Dosage amounts and scheduling, treatment duration and response, progression-free survival
& overall survival, and combination treatments were all areas of discussion
in these roundtables.
one other meeting took place early Monday morning -- that of the International
Myeloma Working Group (IMWG). This
is a group over 150 leading myeloma experts worldwide (seemingly all of the
"heavy hitters" from what I could tell) who tackle projects and publish papers
on subjects that help our local oncologists as well as patients. You can find published papers at www.imwg.myeloma.org on such topics as allogeneic stem cell
transplants and peripheral neuropathy.
Future papers may include recommendations and/or guidelines on topics
such as maintenance and high-risk treatment.
I, for one, will be watching this site more carefully.
was such a busy day, and yet the actual International Myeloma Workshop
officially kicks off tomorrow (Tuesday).
I arrived in Paris yesterday (Saturday)
and spent a bit of time walking in the city... mostly to make sure I stayed awake
to combat the time change.
been to Paris a few times before and I'm always amazed by looking up at the
facades of tall apartment buildings with their balconies contained by iron
railings and ornate decorations. I
remember remarking during my first visit that one could take almost any
"ordinary" Paris building and plop it in the middle of San Jose (where I live)
and it would be an incredible historical architectural landmark.
And, of course, eating is also important
to combat the time change. Parisian breads (baguettes, croissants) and cheeses are excellent
sources for "time-change" management. But I'm not sure how to explain my
continued inhalation of these several days from now (grin)!
Did you know that May 1 (May Day) is a
big holiday in Paris? Today, many
roads and stores are closed. Guess
I'll walk somewhere for my daily bread and cheese. I'll need to stay fortified for the upcoming back-to-back meetings of the International Myeloma Workshop!