A Patient in Paris

Revlimid Maintenance Overall Survival Benefit Shown

2011-05-10T16:58:32Z

Hi Folks,

I've 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:

1) Revlimid maintenance showing an Overall Survival benefit after two years; and

2) Secondary 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.

Both of these conclusions also need longer study times in order to confirm results.

Regarding 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.

I 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.

Finally, 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 decisions?

And 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.

Getting 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.

Here 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.

Best wishes for all of our good health.

IMW 2011 Topics: Declining Mortality Rates, New Drugs

2011-05-07T02:20:51Z

Day 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.

From 85% 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.)

Deep 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!

Bone 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.

Various 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).

Finally 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 novel drugs.

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.

I 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 discussed.

Let 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.

Determining MM Treatment by Risk Category

2011-05-07T01:45:55Z

Additional news from Day 3 of the International Myeloma Workshop in Paris:

I 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.

"Try 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.

However, 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 opinion."

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, or placebo's.

Overall Survival Gains on Revlimid Maintenance

2011-05-06T05:51:24Z

Day Three of the International Myeloma Workshop arrived bright and early this spring day in Paris.

The schedule was filled with important discussions: Secondary Malignancies in Myeloma; Optimizing Patient Outcomes; Newly Diagnosed Patients Over 65; and New Drugs and Therapeutic Approaches.

But 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 placebo.

Further, when folks on the placebo switched to Revlimid maintenance, they also experienced OS gains.

That 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.

Many 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.

In 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."

And 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 respectively.

As 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.

The last day of meetings begins at 7:45 a.m. In the afternoon, I'll be at the IMF patient-family seminar.

Au Revoir

Considering the Future of Myeloma Treatment

2011-05-05T00:39:20Z

Day 2 of the International Myeloma Workshop

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 management.

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 maintenance.

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.

As No Two People Are Alike, No Two MM's Are Alike

2011-05-04T06:22:57Z

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).

Did 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.

Today's 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.

We're 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.

At 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."

That's 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 techniques.

I 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."

Bone 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 recommended.

There 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.

Finally, 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 2.

Issues That Matter to Myeloma Patients

2011-05-02T22:44:30Z

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 session.

Leading myeloma specialists, procedural specialists (e.g. orthopedic back specialists), and representatives from companies talked about issues important to myeloma patients.

The 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.

For 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 versus tolerable?

2) How does treatment and safety effectiveness of kyphoplasty compare with vertebroplasty and non-surgical management of back pain?

3) What are the best imaging techniques (bone survey, MRI, PET and CT scans) to determine treatment decisions while considering insurance reimbursement?

Roundtable 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.

Finally, 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.

It was such a busy day, and yet the actual International Myeloma Workshop officially kicks off tomorrow (Tuesday).

Whew!

Greetings from France!

2011-05-01T19:04:38Z

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.

I've 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!

Au Revoir

Jack

Packing and Prepping for Paris

2011-04-30T17:52:23Z

During the last few days before leaving for the International Myeloma Workshop in Paris, I started prepping for these meetings. That meant going to the IMW website and reviewing the agenda and examining abstracts that might be available.

I'll attend all of the meetings, which begin Tuesday, May 3, but I'm sure some presentations and results will be more interesting and relevant to patients who are looking for near-term answers.

For example, Tuesday's meetings will focus on molecular pathways, genetics, cell biology and animal models. While that research is critical to successful drug and treatment development for personalized medicine, I don't know if information presented will make a difference in our decision-making today.

Yet, I'll bet that if I had attended the first IMW 13 years ago, I would be able to point to available treatments today that came from laboratory research presented back then.

I'm really looking forward to hearing presentations Wednesday, Thursday and Friday that focus on topics such as optimizing patient outcomes, treatment protocol comparisons, new drug--as well as maintenance--results, and minimizing side effects.

We always ask questions about transplants (sooner, later, or not at all), whether or not to treat early stage myeloma, what's the best treatment for me, how long should I continue treatment/biophosphonates/maintenance, and can dosages be reduced.

So now, I'd better start packing.

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Eagerly Anticipating News from the IMW Conference

2011-04-22T22:37:43Z

As a 16-year survivor of multiple myeloma, when I was given the opportunity to attend the May 3-6, 2011 International Myeloma Workshop in Paris and blog about it from a patient's perspective, I said "absolutely."

After all, the ASH (American Society of Hematology) conference was only five months ago, but so much has happened since then. I'm looking forward to passing along that news to you in this blog.

For example, one of the studies the IMF is excited about shows overall survival on maintenance for the right myeloma patients. Other news we'll be hearing from presenters in Paris are updated results from trials using Carfilzomib, Pomalidomide and many more drugs.

A bit of background about me: Sixteen years ago, I was diagnosed with Stage 3 multiple myeloma. In 1998, I had a full allo transplant using my sister's stem cells. While I battled graft-versus-host disease and had three plasmacytomas radiated during the next two-to-three years, I've been in a complete remission with no treatment for the last eight years.

However, I believe that one day my myeloma will return. While I'm not medically trained, I've stayed in close contact with the myeloma community and seen amazing research and treatment results over the last 10 years.

I've been fortunate enough to have attended the last five ASH conferences and shared results with our S.F. Bay Area myeloma support group and others around the country.

The Paris presentations, according to the agenda, will start before 8 a.m. and continue until at least 7 p.m. I am excited to share what I learn from this jam-packed event with you!

Stay tuned...