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April 2012 Archives : Myeloma Voices

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"It's a journey I would have never chosen."

For most of us, that is true. It's true for me. It's true even though, frankly, some of the gifts from being on this path have been huge. I wanted to write a bit about some people I have met in my six-plus-year odyssey as a myeloma caregiver wife, who DID choose this journey. 

My husband, Alan, was diagnosed in September 2005. I jumped on the research and searched for resources quickly. The IMF was one of those resources. I remember ordering the large bag of pamphlets about multiple myeloma, and the arrival of the card for a Patient and Family Seminar in San Francisco. That seminar happened to hit on the day of my 50th birthday. We traveled from Portland to San Francisco, and were like sponges absorbing information. I remember the rush of calm when a patient panel included a 28-year survivor. 

At a cocktail party that evening my extremely introverted husband whispered to me "Don't make eye contact!" He was shy in a room full of strangers. But Alan married an extreme extrovert, so of course I made eye contact, and invited a couple looking for a place to sit to join us. 

It was Ms. J and Mr. J from Medford. They were delightful. Alan was immediately fascinated with Mr. J's extensive notebook of years of lab results. They both "engineer" types, and Alan started keeping similar spreadsheets of his lab results when we returned to Portland.   

I've held onto this couple's story for years.  They were several years older than us and had been dating for a long time before Ms. J said "yes" to a marriage proposal. The wedding was just weeks away when the myeloma diagnosis came. There was a lot of pressure from her family to call it off and to avoid a marriage as a caregiver to a myeloma patient. But she didn't back out. 

How hard it must have been to choose to say "yes," not knowing what the future might be, and with well-meaning family trying to dissuade you. By the time Alan and I met them, things had developed into a pretty nice routine of golf and clinic appointments, and the marriage was a treasure to both. 

We threw ourselves into our local myeloma community. Because of this, when friends of friends had a family member who had been diagnosed with myeloma, we often found ourselves connected with them to "show them the ropes." This was how I met Ms. C, who was gathering information after her fianc� was diagnosed with myeloma. She was in her 40s and finishing a medical program, and he was approaching 50. She wanted to talk to someone about what it was like to marry someone with a myeloma diagnosis.  I shared what I could about choices and obstacles.  

Ms. C also chose to be the wife of a myeloma patient.  In the brief window before her new husband began Revlimid treatment, she became pregnant. The couple's little son has the widest smile I have ever seen on any human being, and is the center of their universe.  

Two weeks ago, I was at the IMF's patient and family seminar in Seattle, and met Ms. S, whose boyfriend of almost five years was recently diagnosed. She is selling her house, and he is packing up his, to move to the East Coast together, where they have decided his treatment will be handled. Her sweetheart asked Ms. S not to share his diagnosis with friends and family, partially, I think, out of worry over the judgments they might make on her choosing to accompany him on his challenging future. But she is smart, loves him, and is choosing with her eyes open. 

I hope all three of these caregivers find gifts along the way that exceed the challenge of choosing to accompany someone with myeloma on this uncertain path. If your story is similar, you, too, have my extra admiration.


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A recent publication in New England Journal of Medicine brought to attention the fact that tumors do not have a single genetic type or signature.  Multiple biopsies revealed diverse genetic patterns within the same cancer samples in the same patients.  No longer can we rely upon a single biopsy to tell the whole story.  Perhaps even more sobering, we need to get used to the notion that planned therapies must encompass considerable genetic diversity and not target a single mutation, which most likely will be only one of a host of mutations.  Commentaries in the Wall Street Journal and from Reuters (London: Kate Kelland) emphasize the same points.

So what does this mean for developing new and better therapies for myeloma?

Firstly, multiple genetic abnormalities (or mutations) are a characteristic feature of myeloma.  When myeloma bone marrow samples are checked, typically numerous chromosomal (or genetic) changes are found.  The potential for multiple genetic subtypes has been known for many years.  In 1984, I questioned whether it was helpful to describe myeloma as a "monoclonal disease" when obviously many genetic subclones were evident at the molecular level (Brit J. Haematology, 1984, 57, 357-363) What is confusing is that the subclones frequently continue to produce the same monoclonal protein, thus masking the underlying heterogeneity.  In a follow-up paper in 1985, I showed that new subclones with additional genetic features are responsible for relapse, and that these new genetic features are part of what can be called "sequential clonal evolution" or stepwise changes that produce myeloma cells resistant to treatment.

So myeloma is sneaky: it can evolve over time.  Multiple pathways within the myeloma cell are involved.  The end result is that no single drug is likely to shut down myeloma cell growth because too many side or back-up pathways can work around any blocked path. In addition, the pathways are going to vary from myeloma cell to myeloma cell and from patient to patient.

This is why combinations of drugs are so important to block off escape routes to renewed myeloma cell growth and further mutations and evolution.  Targeting key pathways is crucial--but not just one pathway!  Some drugs, such as IMiDs (eg. Revlimid), we know are multifunctional.  This means they have effects upon multiple pathways, and that may be a major aspect of the benefit of these agents.

As far as the exact chromosome abnormalities found in myeloma, such as loss of chromosome 13, loss of part of chromosome 17 (17p-), and translocation t(4;14), there are not as yet drugs that target specific pathways affected by these chromosomal changes.  Nonetheless, it appears that Velcade� has particular benefit in patients with t(4;14).  It may turn out that using drug combinations that shut down multiple pathways may be broadly effective for a majority of patients.  Of note, the combination of Velcade (or carfilzomib) plus Revlimid plus dexamethasone (VRD) has substantial benefit for >95% of newly diagnosed patients.  So, without knowing exactly why it works so well, the strategy of multi-pathway blockade seems to be unusually successful.  Studying patients who fail to have success with VRD (or CRD, Cytoxan + Revlimid + dexamethasone) should prove to be especially revealing.

Thus, although the idea of personalized medicine is instantly appealing, it may be that broader strategies to include a majority of patients will prove to be both simpler and more effective.

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