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Wednesday, April 23, 2014

Jet Setting

Tonight Gretchen and I are flying off to Dublin, Ireland to attend a wedding on Saturday.  Son Jeff and his girlfriend Christine are joining us on the flight over.  We will then drive from Dublin to Shannon tomorrow to pick up daughter Holly and her boyfriend Ryan, who will be coming in from San Francisco.

The bride is one of Holly's childhood friends.  The wedding will be in a quaint resort town called Coolbawn Quay, in Co. Tipperary, not far from where my paternal ancestors lived.  All of us will get in some touring of Ireland both before and after the wedding.  From there, Jeff and Christine are headed off to Turkey, while the rest of us go on to Barcelona, Spain for a few days before returning home on May 4.  We're all really excited about this trip!

This is our first major trip since Gretchen's accident, so we will have to take it a bit easy.  Despite my MM and her head injury, we are both fortunate to be able to travel and see the world.  We want to get as much of this in as we can while we are still able.

Needless to say, I won't updating this blog until I get back.  My next visit to the Farber is on Monday, May 5, so I should have some updated news to report then.  

Our house is going back on the market today.  We have hired a "stager" to change things around to make the house "pop".  This will all occur while we are away, so the house will have a new look when we get back home.  We're glad to have the house shown in our absence.  It's a real pain to have to keep everything in show condition while trying to live a normal life.  Hopefully, we'll get some nibbles while we are traveling.

Friday, April 18, 2014

Immunotherapy Research

I've been doing a little more research on the exciting new research direction of harnessing the body's own immune system to fight cancer.  One of the most promising areas of research involves activating the body's T cells.  I'm going to try to give a layman's explanation of this, which I hope is not full of you know what.  Bear with me here.

electron microscope photo of T cell
T cells are a type of white blood cell that are the immune system's strike force against foreign invaders and diseased cells.  Antigens from the cancer cells are collected by antigen-presenting cells (APCs) and then transmitted to the T cells, along with a trigger protein, B7, which tells the T cells to attack.  The T cells are then sent on a search and destroy mission against the cancer cells.  T cells have a protein receptor, PD-1 (aptly named Programmed Death-1), which allows them to destroy cells that they contact.  In order to keep the T cells from destroying healthy cells, all healthy cells have a protein co-receptor, PD-L1.  When PD-1 is bound by PD-L1, this turns off or deactivates the T cell, thus saving the healthy cell.

The T cells also have another protection against destroying healthy cells. A receptor called CTLA-4 on the T cell itself can prevent B7 from doing its job in order to “keep the brakes on” the immune system.

Now I'm going to turn to literature.  I just recently read John LeCarre's famous spy novel, Tinker, Tailor, Soldier, Spy.  In it, the British spy, George Smiley, battles his Russian spy nemesis, Karla, who has planted a high-level mole in the British spy network, MI5.  In this story, Smiley tries desperately to uncover the secret mole who is undermining Britain's defenses.

Here, the cancer is Karla, and the cancer researchers trying to unravel this mystery to protect the immune system represent George Smiley trying to protect Britain.  The cancer, like Karla, is brilliant, resourceful, and difficult to beat.  The cancer mole managed to penetrate the immune system.  It has essentially stolen the PD-1/PD-L1 mechanism from normal cells in order to evade attack by the immune system!  However, as with Smiley, cancer researchers are ingenious, dogged, and determined.  They have recently discovered this mole in our cancer defenses and are now mounting a counter attack.

PD-1 inhibitors have been developed and are now in clinical trials.  The graphic below shows the mechanisms for breaking the bond between PD-1 and PD-L1, allowing the T cells to continue on their search and destroy mission.  Other antibodies are also in testing to inhibit the CTLA-4 receptor on the T cells, allowing them also to proceed to attack the cancer cells.
How PD-1 inhibitors activate T cells against cancer cells

There is an interesting discussion of these research approaches along with some of the ongoing clinical trials at this website:  Some of the monoclonal antibodies, such as Nivolumab and Ipulimumab, are showing promising results in clinical trials.  So far, the most dramatic results have been for melanoma, non-small cell lung cancer and kidney cancer, but these results should be encouraging for MM research as well.

One of the interesting things about immunotherapy is that the results seem to last longer than the therapy itself.  Once the T cells have been armed with the immunization, the results seem to be be very durable, even after the treatment has been discontinued.

I hope I haven't bored you or overwhelmed you with technical stuff.  But I like to have a picture of what is happening in MM research and I'm very encouraged by this approach.  I was happy to notice that Dana Farber has been on the forefront of this research.  Dr. Gordan Freeman of DFCI led the discovery of the PD-1 protein.

It's all good.

Wednesday, April 16, 2014

Iron Deficiency

As many of you probably know, I have been anemic for quite a while now, long before my MM diagnosis.  I first noticed my weakness and shortness of breath on our family vacation in Switzerland in December 2008.  I could barely ski, and I found myself lagging the rest of the family walking up the hill to our rented condo.  After that, I saw my PCP, who prescribed iron pills.  After about 6 months, I was still anemic and I was referred to a hematologist, who prescribed Vitamin B12 instead of iron.

All of this persisted for another couple of years, during which I was often tired.  I finally got diagnosed with Lyme disease, and after several months of high-dose antibiotics, I felt better.  But my anemia never went away.  My hematologist never figured out the source of my anemia.  When I was diagnosed with MM in July 2011, I exhibited only one of the four standard CRAB symptoms (elevated Calcium, Renal problems, Anemia, or Bone lesions).  In my case, it was anemia.

I am recounting this background to put my current situation into perspective.  In January, I was found to be iron deficient, so I have been taking Ferrex iron pills since then (250 mg, 2x a day).  In March, my iron levels were about the same, which puzzled me.  After 300 mg/day of iron pills for two months, shouldn't things have gotten better?  I don't know, I'm not a doctor.  I brought this up to Dr. Richardson's nurse, Mary, at my last visit and told her I was a bit concerned about it.  She didn't think it was anything to be concerned about, but she agreed to bring it up with Dr. Richardson.  I also agreed to have a fecal occult blood test done with my PCP to see if there was any internal bleeding.

On Tuesday, Mary called me to say that Dr. Richardson had no explanation for the results, so he suggested that I get checked out by the Benign Hematology Group at the Farber.  So I now have an appointment in June to meet with one of their physicians during my normal monthly visit.

In the meantime, I obtained a fecal occult blood test kit from my PCP, Dr. Guidi,  and sent it in early this week.  I just got a call from Dr. Guidi's nurse today saying that the results were normal.  Phew!  That's good news.  I was concerned that there might be a source of bleeding somewhere in my digestive system that was depleting my iron level, but that seems to be ruled out now.

Maybe I'm supposed to just keep on taking iron pills for an indefinite period and hope everything is OK, but that just doesn't seem right to me.  There must be some underlying cause, and I would like to get to the bottom of it.  Maybe I'm being overly concerned, but I want to take control of my situation and not just let things dawdle along.  I'm happy that Dr. Richardson suggested getting another hematologist involved.  I'm also glad that I am being proactive in pushing for answers.  After being anemic for over 5 years, I'd really like to know why.  Maybe it has to do with the MM or the Revlimid side effects, but then again, maybe not.  I'm looking forward to finding out. 

Monday, April 7, 2014

Maintenance Cycle 21

Today was my Farber day.  Fortunately, my numbers continue to look good.  My neutrophils were at 1.76, a little below normal but still well in the range for me to continue on the Rev maintenance.  My hematocrit (HCT) actually went up to 37.9, the highest reading since I was diagnosed back in 2011!  That's good news.  Last month it was at 34.8.  Maybe the iron pills I've been taking for the last three months are having a salutary effect.  I'm still anemic, of course, but other than getting tired easily, I feel really good.  I'm not ready to run the Boston Marathon, mind you, but I can still take a fast walk to my mailbox.

In other news, my knee is still feeling good from my meniscus tear and osteoarthritis.  The cortisone shot I got in September seems to be still working, which is great.  I have been a little lax about getting to the gym to follow through on my PT exercise regimen.  However, I had to get out of the house Saturday because Gretchen was hosting a "Goddesses" get together with her women friends.  Not a place I wanted to be, and the feelings were quite mutual.  I just had the excision surgery for the squamous cell skin cancer on my arm on Wednesday, and I was told not to do anything for a several days (like bend over, etc.) because of the stitches.  Yeah, right!  As a sop to Molly, the surgeon, I decided to forgo my upper-body exercises, but I did 30 minutes on the bike and then just worked on my leg muscles.  It must have been OK, because I didn't start bleeding to death afterwards.  Oh yeah, and I think I did bend over a couple of times.  Sorry, Molly.

There is lot of exciting recent news on alternative approaches to treating MM.  Up until now, the standard therapy approach consists of a multi-drug combination including a proteasome inhibitor, an immunomodulatory (IMiD) drug, and a steroid (dex).  While these classes of drugs are continually being improved (e.g., Kyprolis, MLN-9708, Pomalidomide), this new research is looking outside the box in the hopes of finding the Holy Grail of cancer treatment leading to a cure, not just remission.

Today's blog by Pat Killingsworth featured recent research results using T cell and vaccine immunotherapy.  Here is a link to his post:  T cell therapy is a way to use a patient’s own immune system cells to target and eliminate myeloma cells, either by waking up and empowering T cells through engineering (called CAR T cells)  or using a vaccine to stimulate the T cells to do their job.   One of the vaccines being studied is  nivolumab, which can release the brakes on an immune system attack on cancer. The drug blocks PD-1, a protein on the immune system T cells that restrains them from leading an assault on tumor cells.  (By the way PD stands for programmed death...great name!)  By interfering with the PD-1, nivolumab allows the attack to proceed.

In today's issue of "Inside the Institute" that I picked up at the Farber, there was a summary of a recent article in the "Journal of Clinical Oncology", which showed remarkable results using nivolumab in patients with advanced melanoma.  Hopefully, some of the clinical trials now underway for MM patients will show similar results.  By the way, considering my proclivity for various types of skin cancer, I'm heartened by the good results shown using nivolumab for melanoma. You never know.

It's a race against time.  Will they finally find an effective treatment for MM while I'm still around to benefit from it?  I'm very optimistic that they will.  Cheers.

Wednesday, April 2, 2014

This and That

This winter has been a bitch.  Snow still covers a lot of our yard.  Normally, I would have been out by now fertilizing and getting ready for spring, but the vestiges of winter still surround us.  Sigh.  Sometimes I wonder why we live here.  Anyway, the next few days are supposed to be somewhat more spring like.  Whoopeedoo!

Today I had the second surgery for my squamous cell skin cancers.  I'm used to being poked and prodded, so it was no big deal.  This one was on  my right forearm.  I just hope she found the right spot to remove.  The scar on my right cheek is healing nicely, so I presume this one will as well.  Thank you, Dr. Molly MacCormack!  And you know what?  If it doesn't, I really don't care, as long as the cancer is gone.  That's the only thing that matters.

I wonder if my recent spate of skin cancers might be related to my MM therapy.  The chemotherapy drug melphalin I took to kill all my bone marrow cells prior to my transplant has been linked to secondary cancers.  In addition, the Revlimid I've been taking has also been associated with an increased risk of secondary cancers.  Could my latest bout with skin cancer be caused at least in part by my MM therapy?  Who knows?  In any case, I will continue to be vigilant about any more of these.  I have another appointment in late July with my dermatologist, Dr. Reohr.  I plan to keep on top of this.