KSTP Channel 5 Story

Last week KSTP TV, the Twin Cities' ABC affiliate, interviewed me and my gals for a 2-minute piece about our running, 50 states, cancer, and whatnot. That story showed on the news Sunday morning, June 17, and is now on the internet here.

One of the reasons we run is to raise money for Team Continuum and Tackle Cancer Foundation. If you feel inclined.

Highlights from ASCO 2012

According to me. I'm not a doctor, I'm an impatient patient, and pretty choosy about my highlights. They have to be about myeloma in some way, and should have the potential to affect my own myeloma journey.  Here are three:

• Carfilzomib and Pomalidomide continue to star: Carfilzomib is a new proteasome inhibitor, similar to Velcade, but without the neuropathy and with the ability to help some people for whom everything else has failed, including Velcade. Pomalidomide is a new immunomodulatory drug, like thalidomide and Revlimid, but with fewer side effects and with the ability to help some people for whom everything else has failed, including Revlimid and thalidomide. Studies also show that these two drugs together are amazing with newly-diagnosed patients. Both drugs are on track for possible FDA approval yet this year. Two more arrows in the quiver, possibly better than any of the other arrows.
  
  
• Elotuzumab: This strange duck is a monoclonal antibody, similar to the antibodies that our own body creates. It specifically seeks and destroys goofy plasm cells (myeloma cells). For some reason, though, it doesn't work by itself. It wants company. When added to Revlimid, it can often turn the disease around even in patients for whom Revlimid is failing. So far it has been used mostly with patients whose previous treatments have failed, but the work goes on.
  
  
• Zometa isn't so bad after all: The pendulum has clearly swung again, from Aredia (pamidronate) back to Zometa (zoledronic acid). Yes, it causes more osteonecrosis of the jaw (ONJ), in as many as 4% of patients compared with 1% for Aredia, but it has advantages: (1) The infusion time for Zometa is far shorter than the infusion time for Aredia; (2) Fewer infusions are needed; and (3) Most important, Zometa has an anti-myeloma effect of its own, and in a recent study people on Zometa actually lived longer than people on Aredia. So go for the Z, but get your dental work done first, and brush and floss like crazy.

For more, visit the other five posts from ASCO:

• ASCO Post # 1 Saturday morning, the Rajkumar tutorial - how to treat new patients.
• ASCO Post # 2 Sunday morning, the other really good myeloma stuff.
• ASCO Post # 3 More from Saturday morning.
• ASCO Post # 4 Monday, Immunotherapy.
• ASCO Post # 5 Monday, big myeloma poster session.

That's it from ASCO. We're riding the train home.

A new park along Chicago's Lakeshore Trail just south of McCormick Place, site of ASCO:

ASCO 2012 - Blog Post # 5

Monday Posters
Revlimid and Stem Cell Collection:

Dr Divaya Bhutani performed a retrospective review of 310 consecutive patients, and discovered that patients who had been on Revlimid may require one more collection session that patients who had not. However, there was no difference in recovery after their stem cell transplant.

Second Primary Cancers in Myeloma Patients:

Dr Giampaolo Talamo, Penn State University, performed a retrospective analysis of the records of 320 consecutive MM patients between 2006 and 2010. Two conclusions:

• Most patients had already experienced some form of cancer before their myeloma. For them, myeloma was the second cancer.
• Their data did not indicate that Revlimid could be a carcinogenic factor in most of the second cancers they found among their patients.

Rescue by Second Autologous Transplant

Dr Wilson I. Gonsalves, Dr Shaji Kumar, and others at Mayo Clinic examined the outcomes of 105 patients who underwent a second auto transplant for relapsed myeloma. Five percent died, but the rest achieved a median survival of 33 months. Those who had a long-duration response to their first transplant fared best.

Prognostic Value of LDH in Myeloma:

Dr Krina K. Patel examined records of 1247 myeloma patients all the way back to 1974 to determine the correlation between lactate dehydrogenase (LDH) at diagnosis to their length of survival. A value of 300 IU/L was the threshhold. She found that those with LDH greater than 300 IU/L lived just 16 months, while those with HDL under that mark lived 47 months, about three times as long. I don't know if this is really news, but it does appear that LDH can be used as a poor-man's cytogenetics, flagging those patients who are now called "high-risk."

Revlimid/Dex Long Term:

Dr Geetika Srivastava and others at Mayo Clinic studied 286 consecutive patients who received Rev/dex as initial therapy. The overall response was 86%, and, for those, the median time to first disease progression (for those who did not follow with an immediate transplant) was 25 months. Median overall survival was 7.4 years for those 65 and under, 6.2 years for those over 65. Conclusion: It works.

ASCO 2012 - Blog Post # 4

Immunotherapy for myeloma - three papers
All three describe studies with agents having names ending in "mab," which means monoclonal antibody.

Siltuximab with Velcade:

Dr Robert Z Orlowski. In this Phase II study, siltuximab did not provide benefits sufficient to outweigh its side effects. However, Dr Orlowski is still hopeful that siltuximab might be of benefit in different in combination with other agents. Such a study is currently underway with high-risk patients.

"There is no failure, only feedback." - Robert Allen

Daratumumab:

Dr Torben Plesner described the results of a Phase I study with a small number of patients who had received at least two prior therapies, most of them including a stem cell transplant. The early data showed a good response, and the maximum tolerable dosage has not yet been found. This is a good one to watch.

Elotuzumab:

Dr Philippe Moreau. Elotuzumab is a humanized monoclonal antibody targeting a protein which appears almost exclusively on myeloma cells. In this Phase I/II study with patients having 1 to 3 prior therapies, elotuzumab was added to Revlimid/dex and the combination produced a very good overall response rate of 84% with only modest side effects. This drug shows no benefit when given alone, but substantially increases the effectiveness of Revlimid, and quite likely other drugs. Further, there is an optimum dosage; the study showed that a dose of 10 mg (per meter squared) actually produced better results than 20 mg. Makes you wonder if 5 would be even better.

ASCO 2012 - Blog Post # 3

Yesterday (Saturday), Dr Rajkumar from Mayo Clinic presented a tutorial on the treatment of newly-diagnosed myeloma patients. Here are a few more interesting nuggets from that day's presentations and poster sessions:

Transplant Eligibility:

Would you transplant this man? Clint Eastwood is 82 now, but Dr Amrita Krishnan thought perhaps he might nevertheless be a candidate for transplant. Her point was that numerical age is not itself a factor. Rather, the physical issues ("comorbidities") that often come with age are factors, by themselves, including kidneys, heart, liver, and other diseases such as diabetes.

Pomalidomide and Dex with Clarithromycin:

Clarithromycin (Biaxin) is an antibiotic, available by prescription since the 1970s. Since at least 2001, researchers have known that it has an anti-myeloma effect when added to dexamethasone or other standard myemoma therapies. In this study, Dr Adriana C. Rossi demonstrated a significant and sustained response to this 3-drug combination in heavily pretreated patients, better than pomalidomide/dex without clarithromycin.

Baseline Sensory Deficits Predicting Neuropathy in Treatment:

Dr Elisabeth G. Vichaya measured patients' sensory detection before treatment with chemotherapy, and compared that with the neuropathy that patients experienced in chemotherapy. She found:

• Patients who were initially less able to detect sharpness (e.g. a pin) experienced LESS pain and numbness than others;
• Patients who were initially less able to detect warmth experienced MORE pain and numbness; and
• Those with lower initial skin temperatures also experienced MORE pain and numbness.

She thought perhaps that information could be a factor in helping doctors choose the best therapy for a patient.

ASCO 2012 - Blog Post # 2

ASCO deals with all cancers, not just blood cancers, and many sessions are taking place at once. However Sunday, June 3, was "Myeloma Day." That session ran from 8:00 am to 11:00 am and included 12 talks. Some were rather researchy (new word) but several were of immediate interest.

Carfilzomib/Revlimid/dexamethasone (dex):

At the ASH conference in December, Dr Andrzej J. Jakubowiak had showed that the combination of carfilzomib, Revlimid, and dexamethasone was extremely effective for newly-diagnosed patients. Today Dr Jakubowiak showed that extended treatment produces even better responses, with over 64% achieving a "stringent" complete response, where no myeloma cells can be identified by the best measurement techniques. Further, responses appear to be very durable over time.

Bendamustine/Velcade/dex:

Dr Philippe Rodon of France described a study demonstrating that bendamustine, an alkylating agent, can help some heavily-pretreated patients when added to a Velcade/dex regimen. This may be true even when the patient's disease no longer responds to Velcade/dex.

Panobinostat/Velcade/dex:

Dr Melissa Alsina described a Phase II study showing that panobinostat, added to a Velcade/dex regimen, can rescue some patients whose myeloma has proven resistant to most treatments, including Velcade/dex. The overall response rate was 31%.

Carfilzomib versus Velcade:

Both of these drugs are proteasome inhibitors - they target a particular part of the cell, especially plasma cells. The two drugs have not been compared in a head-to-head study, but Dr Robert Orlowski did his best to compare them anyway, using data from comparable studies. A study of carfilzomib/melphalan/prednisone, and another of Velcade/melphalan/prednisone showed almost equal efficacy, though Velcade caused more neuropathy. Carfilzomib is looking good, but all studies of Velcade have used intravenous Velcade. Modern comparisons should use sub-Q Velcade, and once-weekly at most.

Cyclophosphamide/carfilzomib/thalidomide/dex:

Ouch. Dr Joseph Mikhael presented the results of this 4-drug study, with newly-diagnosed patients. It achieved a high response rate, 83% "very good partial response," but at the cost of many Grade 3 toxicities. Grade 3 is severe enough to significantly interfere with a patient's health or comfort, and generally requires a dosage reduction. Dr Orlowski suggested dropping the thalidomide and trying just the other three.

Bisphosphonate Therapy:

Dr Gareth J Morgan described studies showing that Zometa, compared with Aredia, results in a significant improvement in overall survival (!). Zometa causes more osteonecrosis of the jaw (ONJ), however, almost 4% reporting it, compared with 1% for Aredia. Most of the ONJ occurs in the first 36 months of treatment. ONJ appeared to be less in patients being treated with thalidomide. Some of the ONJ events seemed to be related to dental procedures.

Pomalidomide/dex:

Dr Ravi Vij described a study comparing showing that pomalidomide can be effective in a population of heavily-pretreated patients whose myeloma is resistant to both Velcade and Revlimid. In one arm of the study, patients got pom/dex, while the other arm received pom alone. Response rate was 30% for the dex arm, and 9% for the pom-only arm. The difference in time of survival was not as dramatic. Bottom line - take your pom with dex. Sorry about that.

MLN9708:

This is an exciting new proteasome inhibitor, like Velcade and carfilzomib, but can be taken at home as a pill. Dr Sagar Lonial described a Phase I study with heavily-pretreated patients. A Phase I study is designed to find the maximum tolerable dose of a drug, and determine other safety factors, rather than to determine the drug's treatment efficacy. However, many of these patients did achieve good responses or stable disease. There was very little peripheral neuropathy.

ASCO 2012 - Blog Post # 1

Dr. S. Vincent Rajkumar, of Mayo Clinic in Rochester, MN, outlined what seems to be Mayo Clinic's current standard of care for newly-diagnosed patients. Title: Upfront Therapy for Myeloma - Tailoring Therapy Across the Disease Spectrum. This is a very significant talk. With it, he presented a flow chart for determining the best initial treatment for a newly-diagnosed patient.

He suggests first stratifying a patient's disease according to risk as determined by cytogenetic testing (wacky chromosomes) or by unusual espressions of disease:

• The highest-risk patients typically live only two to three years after diagnosis, and not much has been done to improve that. His description of treatments for these patients is beyond the scope of this blog post.
• Medium-risk patients are those with a specific genetic translocation (t4;14), which he says can be converted to standard-risk by the use of Velcade. Not some other novel drug, but Velcade.
• Standard-risk patients have a wide array of available treatments before them, and the real question for the doctor is, which should s/he recommend.

He then suggests classifying the standard risk patient once more, according to eligibility for transplant, determined not so much by age as by health factors such as diabetes, kidney disease, heart disease, and other "comorbidities." For those eligible for transplant:

• Use Revlimid/dexamethasone (Rd) or Velcade/cyclophosphamide/dex (VCd) as an induction regimen for four cycles. To reduce the risk of treatment- limiting neuropathy, Velcade should be given once weekly, not twice weekly, or given subcutaneously.
• If the patient achieves a good response after four cycles, then stem cells can be harvested and stored.
• After stem cell harvest the patient may be offered the choice of an immediate autologous stem cell transplant (ASCT) or continued treatment with the induction regimen.
• A transplant is an aggressive treatment approach by any measure, aiming for a complete response but carrying significant risks, while the continuing induction regimen can be thought of as the beginning of a "sequential disease control approach that emphasizes quality of life as well as survival." In this second approach, another regimen will be tried when the original one fails. At present there are no data showing clear superiority of one approach over the other.

Transplant ineligible patients are usually elderly and have medical complications. Some points:

• Rev/dex (Rd) is commonly used in the USA. The optimum duration is not clear, but dexamethasone is usually lowered to a minimal amount or discontinued after a year.
• Thalidomide/dex is inferior to melphalan/prednisone and should not be used for these patients.
• Melphalan/prednisone/Revlimid (MPR) is not more effective than MP without Revlimid, he says. However, melphalan/prednisone/thalidomide (MPT) is superior to MP alone. An improvement is also likely if Velcade is added to the MP combination, although neuropathy is a risk. Cyclophosphamide can be substituted for the melphalan to reduce side effects.
• Having said all of that, he believes that Rev/dex (Rd) or Velcade/cyclophosphamide/dex (VCD) may be the best choices for this group, just as they are for the transplant-eligible patients. VCD is preferred for patients with kidney issues.

Final thought: The two endpoints that matter to the patient are length of survival and quality of life.


McCormick Place in Chicago is the largest convention center in the USA, and the ASCO convention brings to it over 30,000 clinical oncologists from all over the world.

Mark Fearing Died Today

Myeloma claims another one.  Mark and his wife Carol have been regulars at myeloma support group meetings in Minnesota.  Recently he ran out of treatment options, and entered hospice.  You can pass your condolences to Carol on Mark's Caring Bridge site.

We will miss him.

They Know Me on Sight

I walked toward the hematology desk at Mayo Clinic and was greeted by name before I got there. No one wants to be that familiar at that desk, though of course it's a compliment to the sweet technician who remembered me. Imagine how many people she sees in a day, not to mention a month. Good news again today, though, at the end of the 55th 28-day cycle on the pomalidomide study, my numbers are stable once more.  I'm going to write a country-western song about pomalidomide .. my secret love, takin' me to bed every night, keepin' me alive ...

Cancer markers:

IgG is down about 6%, from 1210 to 1140 mg/dL, but it goes up and down a bit, and the difference may be within the measurement accuracy of the test. M-spike is unchanged at 1.1 g/dL. Lambda and kappa light chains both dropped slightly, though the ratio is about the same and I don't really know what the light chains mean anyway.

For the second straight month every other blood marker of any significance was within the reference range, even the red blood cell count. I feel very good, too, and I'm running well, considering recent surgery. I had been concerned about calcium, but it's been well within the reference range for three months now, so I'm sure I have no dissolving bones.

ASCO:

The annual meeting of the Americal Society of Clinical Oncology (ASCO) will be held in Chicago this coming weekend, and my sweeties and I have been invited to attend. We will be helping to staff an advocacy booth supported by the International Myeloma Foundation, and blogging about new myeloma research. We might even go for a nice run on the Chicago Lakeshore Trail.

Advocacy Issues:

• Early Access to Emerging Treatments: Current rules often prevent doctors and their patients from trying new treatments, even if the patient is dying. We as a nation want to prevent patients from suffering unexpected side effects, of course, but for dying patients the side effect of NO treatment is worse.
• Oral Drug Parity: Some expensive, targeted cancer treatments are administered as infusions in a clinic, while others are pills, taken at home. Because prescription drug coverage almost always has a much higher co-pay and deductible than the medical insurance that covers in-clinic infusions, patients whose best treatment option is a pill can be faced with bills as high as $10,000 per month. Some states have passed legislation requiring insurers to cover oral treatments on terms no less favorable than in-clinic treatments, and federal legislation is proposed.  It can't come soon enough.

More to come ...

Most-Recent Test Results:

Test		Mar 08		Apr 04		May 04		May 29		Remarks
M-spike g/dL		1.0		1.1		1.1		1.1		\ Tumor marker
IgG mg/dL		1100		1290		1210		1140		/ Tumor marker
Lambda mg/dL		2.80		2.24		2.75		2.53		L Free light chains
Calcium mg/dL		10.3		9.6		10.0		9.7		OK
Creatinine mg/dL		1.0		1.2		1.0		1.2		Kidney, OK
HGB g/dL		14.2		14.6		15.6		15.7		Hemoglobin, OK
RBC M/uL		3.86		4.08		4.31		4.37		Red cells, not bad
WBC K/uL		3.7		6.1		5.3		4.6		White cells, OK
ANC K/uL		1.70		1.50		2.70		1.80		Neutrophils, OK

Related Links:

My Myeloma		A discussion of my myeloma, not very technical.
My Treatment History		Not technical.
My Test Charts		Graphic displays of several key test results over time.
My Test Result Table		Somewhat technical. Best with a wide browser window.
My Supplement Regimen		With links to where I buy them.

Everything here is organic except the oatmeal in the meat loaf (we don't know where to get oatmeal that is both organic and gluten free). Yes that's a dill pickle in a sweet potato:

Revlimid and Second Primary Cancers

Newly-diagnosed patients:

Last Monday, May 7, 2012, the FDA issued a Drug Safety Communication which says, in part, "in clinical trials of patients newly diagnosed with multiple myeloma, those patients treated with Revlimid had an increased risk of developing new cancers." These are also called "second primary cancers."

If you are considering Revlimid as initial treatment or as a maintenance treatment, you may wish to read on before you lean very heavily on that FDA statement:

• The FDA statement contains no new information. The facts on which the statement is based are from three well-known studies on newly-diagnosed patients, and are over a year old. If your doctor doesn't already know of these studies, it's time to get a new doctor.
  
  
• Since one year ago, new information about those studies has been made available, and it is not clear to me that the FDA used that information.
  
  
• The three studies are all different, with somewhat different objectives, and none was specifically designed to reveal the frequency of second primary cancers. They were meant to show the difference in progression-free survival and overall survival, comparing Revlimid maintenance with a placebo, after transplant or other initial treatment.  The Myeloma Beacon has a good description of the three studies.
  
  
• Analysis by FDA and others may be wrong, and this may be one reason:
  • All three studies demonstrated that Revlimid maintenance does extend the time to relapse.
  • In some cases the patients on maintenance had twice as much time, or even more, before relapse.
  • Therefore, patients on Revlimid maintenance had much more time to develop second cancers before relapse than did patients on the placebo.
  • It appears that some of the studies, if not all three, stopped looking for second primary cancers once a patient had relapsed.
  • Thus, we would expect patients in the Revlimid arm to collect more second primary cancers, just because they had more time to do so.
  
  
• Even if Revlimid treatment did result in more second primary cancers, that risk may be lower than the risks from not taking it.

Patients with relapsed/refractory myeloma:

The FDA also reviewed results from two clinical trials which supported the initial FDA approval of Revlimid. I find their description of the data to be confusing at best, but in the worst interpretation of it, patients on Revlimid with high-dose dexamethasone experienced fewer than four second primary cancers per 100 patients per year.

Bottom line:

I'm not a doctor, but I have opinions anyway, and in my opinion, the FDA Safety Communication should not be an occasion to change any decisions about using Revlimid, which is still one of the best treatment options available. Other very smart doctors are trying to make sense of this issue as we speak, and we should wait until better information is available.

I admit to a little bias on this issue, because: (1) I take pomalidomide continuously. It is a close relative to Revlimid, and I don't want to think about second primary cancers from that; and (2) I like Celgene, the makers of both drugs. However, I really don't think that we have enough information yet to even say for sure that Revlimid poses a greater risk of second primary cancers than no treatment at all.

Please comment, especially if you have any corrections or suggestions about facts or reasoning in this blog post. Please let me know. Thanks.

We Lost Another One

Mike Olson, from Menominee WI, participated regularly in the Stillwater, MN support group meetings, and was instrumental in starting a support group in Eau Claire, WI.  Mike's myeloma was aggressive, however, eventually overwhelming every treatment Mike's doctors could offer.  After a couragous and exhausting battle, Mike died at home Thursday, May 10, 2012.  We will miss him.

Here is the obituary.

Cycle 54, Still Stable

At the end of the 54th 28-day cycle on the pomalidomide study, I'm happy with the results once again. It's good stuff.

Cancer markers:

IgG is down slightly, from 1290 to 1210 mg/dL, but the difference may be within the measurement accuracy of the test. M-spike is unchanged at 1.1 g/dL. Lambda and kappa light chains did their usual dance, this time lambda chains are up slightly, but I doubt it means anything.

Every other blood marker of any significance was within the reference range, even the red blood cell count. I feel very good, too.

Anniversary:

Sunshine and I have recently begun the 50th year of our marriage. We're having a lot of fun running marathons in each of the 50 states, but 49 years of marriage is far more significant and satisfying.

Most-Recent Test Results:

Test		Feb 07		Mar 08		Apr 04		May 04		Remarks
M-spike g/dL		1.1		1.0		1.1		1.1		\ Tumor marker
IgG mg/dL		1280		1100		1290		1210		/ Tumor marker
Lambda mg/dL		1.99		2.80		2.24		2.75		L Free light chains
Calcium mg/dL		10.2		10.3		9.6		10.0		Normal
Creatinine mg/dL		1.0		1.0		1.2		1.0		Kidney, OK
HGB g/dL		15.2		14.2		14.6		15.6		Hemoglobin, OK
RBC M/uL		4.18		3.86		4.08		4.31		Red cells, not bad
WBC K/uL		4.5		3.7		6.1		5.3		White cells, normal
ANC K/uL		2.40		1.70		1.50		2.70		Neutrophils, normal

Related Links:

My Myeloma		A discussion of my myeloma, not very technical.
My Treatment History		Not technical.
My Test Charts		Graphic displays of several key test results over time.
My Test Result Table		Somewhat technical. Best with a wide browser window.
My Supplement Regimen		With links to where I buy them.

Normal Breakfast: