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The Future Of Myeloma! The Beginning Of The End Of The Death Sentence!

9/25/2016

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What is the future of myeloma? I believe the future is much brighter!   We know myeloma patients who are found in stage 1 have a survival advantage twice that of a patient found in stage 3.  In addition, a patient who is found at 49 years of age or before has a survival advantage of  twice that of a patient found  when greater than 70 years old.  Finally, if found early at the time of high risk of progression smoldering myeloma, a clinical trial with treatment of Lenalidomide and dexamethasone showed only 5% of patients had died in the treatment group at 7 years, and 45% of the watch and wait group had died.  New trials are in the works (CESAR and ASCENT) designed to cure 50% of the high risk smoldering myeloma patients, and obviously if found before stage 1 will extend the life of those not cured.  One might also expect the devastating effects of CRAB (hypercalcemia, renal impairment, anemia, and bone pain and damage) conditions will be minimized.

So finding myeloma in its earliest stage is the key to improving overall survival, early treatment and myeloma cure!  And how is this done?  The answer may just be in the small country of Iceland.  A new clinical trial called iStopMM may be one of the most important events in modern day myeloma care. As part of the iStopMM study, all 140,000 Icelanders over the age of 40 will have their blood samples tested for the precursor to multiple myeloma, or MGUS (monoclonal gammopathy of undetermined significance), as well as find those who are smoldering or who are active but yet to be diagnosed.  Dr. Sigurdur Kristinsson of the University of Iceland discussed this exciting and groundbreaking study with us on September's Myeloma Cure Talk and you can listen to the rebroadcast if you CLICK HERE.  Below Dr. Kristinsson explains the program, and how it fits into the International Myeloma Foundations new Black Swan Initiatives.  

The most important question to be answered is whether this is a viable and cost effective approach?  Can this program be scaled up to where it is not 140 thousand people tested, but 148.6 million people like it would be in the USA?    I say the answer is a resounding YES!   I truly hate the methodology of ICER where they determine the cost for one additional year of life of a patient.  ICER computes a year of life should not cost more than $50,000 to $100,000 per life year, and each myeloma patient's year is only worth .7 years of that for a person without cancer.  All of the new drugs for myeloma like Kyprolis, Pomalyst, Elotuzumab, Ninlaro,and Daratumumab failed this test and had cost per year of life (QALY - quality adjusted life year) of  between $200,000 to $500,000.

I will not bore you with the detail (which is at the end of the post),  but my calculation would show this program will provide an ICER based cost per QALY of just $16,312 per QALY.  Or if I assume a myeloma patien'ts life has the same value as someone without cancer, the cost per QALY is $11,404.  So as you can see this project would be way below the ICER targeted cost per QALY.  However, because in the beginning all people over 40 would have to be tested in the first year, and thereafter just those who turn 40 need to be tested, I made this a 10 year project life.  After the 10th year the cost per QALY goes way down to just  $3521 per QALY.   So as you can see that even by ICER standards the cost per QALY is OUTSTANDING.  The numbers are big, but the payoff is huge as well.  If you want to go though the minutia of the analysis I have included it at the end of this post. 


Good luck and may God Bless your Cancer Journey.   For more information on multiple myeloma survival rates and treatments CLICK HERE and you can follow me on twitter at: https://twitter.com/grpetersen1










The analysis of cost

Data:

US population - 318.9 million
US population over 40 years of age - 46.6%
Percentage of the population who turns 40 each year - 1.25%
Cost for the light chain and M spike test per patient - $150
Number of myeloma cases each year - 30,330
Current life expectancy of a myeloma patient - 5 years
Average age of a myeloma patient - 69 years
Average life expectancy of an American at age 69 -16 years
If treated early 50% of patients are believed to be cured or live an additional 11 years
If treated early the other 50% will live twice the current average or 5 additional years

10 year project cost

First year cost - 318,900 x .466 x $150                  =    $22,291,050,000
Year 2 thu 10     318,000 x .125 x $150 x 9            =        $ 598,000,000
Total 10 year cost                                                          $27,673,000,000


Life years saved

Cure (30,330 x .5 x 11 x10years)                               =           1,668,150
Double life to 10 years (30,330 x.5 x 5 x 10)              =              758,250
Total 10 life years saved                                                           2,426,400

QALY's   (2,426,400 x .7)                                                          1,696,480

Cost per QALY  ($27,673,000,000/1,696,480)             =            $16,312    
Cost per Life Year ($27.673,000,000/2,426,400)         =            $11,404


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The Rosseta Stone For A Myeloma Cure?   Early Treatment Of High Risk Smoldering Myeloma!

9/18/2016

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PictureDr. San Miquel, Ponce de Leon Family Resemblance?
Dr. Irene Ghobrial of Dana Farber Cancer Institute has said a clinical trial must show an OS(Overall Survival) advantage to justify the treatment of myeloma in the high risk of progression smoldering patient population.  Many trials on the smoldering population had been conducted with no OS advantage, until Dr. San Miguel's group in Spain implemented a trial utilizing LD(Lenalidomide and Dexamethasone) vs. watch and wait(the previous standard of care).  The LD arm  showed a significant survival advantage.  This was the study we all hoped would one day provide the key to improved survival and potentially cure.  This study was the key to improved overall survival and cure and is the equivalent of a myeloma Rosetta Stone.

We recently had the honor of having Dr. Jesus San Miguel, the  Medical Director of the Clínica Universidad de Navarra, Navarra, Spain on the Myeloma Cure Panel.  You can hear this exceptional panel discussion if you CLICK HERE.  Some of the key observations from this broadcast include the following.

The trial was called the QuiRedex trial, and enrolled 119 high risk of progression Smoldering Myeloma patients separated into two groups.  One half of the patients utilized the current standard of care, which is to watch and wait until the myeloma becomes active myeloma before treatment is applied.  The second group was treated with Lenalidomide and Dexemethasone.

The results for the LD group was OUTSTANDING.  The time to progression(TTP) for the watch and wait group was 21 months and 85% of these patients had progressed.  In the LD arm 25% of patients had  progression and the average TTP had not been met.  Overall Survival for the watch and wait group at the 7 year mark was 64%.  In the  LD group 95% of patients are still alive.  So if you are High Risk of Progression Multiple Myeloma (HRSMM) and choose to watch and wait, you are 7.2 times more likely to die than if you chose LD treatment.  A significant and outstanding  improvement for HRSMM.

Smoldering patients fall into three different categories, low risk, intermediate risk and high risk of progression.  There are two major classification methods. The main classification for smoldering myeloma is more than 30 grams per liter of M component  and 10% or more of plasma cells in the bone marrow.  The Spanish group uses multiparametric flow cytometry and  when all the plasma cells are clonal, this is considered high risk. Dr. San Miquel believes there is no need to have one consolidated definition, but can have several individual different measurements all of which show risk of progression of 50% within two years.

For a long time there was no rational for treatment because most of the treatments were not effective.  In addition, we could not distinguish between low, medium, and high risk smoldering myeloma, so all smoldering patients were included in the trials. Now there are ways to determine patients with a high risk of progression to active myeloma.  These patients have between 50% and 80% probability to progress within two years.  These patients will not want to wait for treatment if they will progress in two years.  Like breast caner they need to be treated as early in the disease development(HRSMM) as apposed to waiting for it to metastasize. 

New trials are designed to increase the percentage of patients who achieve a cure.  Cure is defined as being in CR(complete response) for 10 years, or MRD (minimum residual disease) negative for 5 years. There are currently two trials for high risk of progression smoldering myeloma, CESAR and ASCENT which are aggressive treatment approaches but with slightly different drug treatment regimens. The CESAR trial is a Spanish study, utilizes the Kyprolis/Revlimid/dexamethasone regimen. The ASCENT trial is a US study which adds daratumumab. Both use stem cell transplant and maintenance.  The prediction is 50% cure for the patients in both trials. In the LD trial there was little genetic information for most of the participants, however in the CESAR trial patient cytogenetic features will be available and followed. The CESAR trial will include MRD tests after induction, SCT, consolidation, and once each year during maintenance.  The MRD test will be by next generation flow and next generation sequencing.

Even though the LD trial had MRD negative patients, Dr. San Miguel  believes the addition of K(Kyprolis) and SCT(stem cell transplant)  will increase the number of patients who achieve cure.  In addition, he believes new myeloma treatments which include targeted therapies should be part of combination regimen.  Myeloma is not a monogenetic disease, and requires more than a single treatment modality.   Myeloma has a complexity of the clones.

Most of smoldering patients have not developed high risk genetic features as is found  in active myeloma currently.   Even in MGUS,  many of the  genetic features are now present in very small quantities as subclones without the capacity to progress, which  are being controlled by the immune stem cells.  Genetics is not the only explanation of  progression and the immune system is a key part of this.  Progressing from MGUS, smoldering, to active myeloma is not only caused by new genetic  abnormalities but includes  proliferation of one of the clones that was there from the very beginning.  The immune system and immune response is a key component in the progression. Mutations will accumulate with time.  So that is why early treatment is important.

For smoldering patients who are low or intermediate risk, Dr. San Miquel would recommend they delay treatment and watch and wait.  The science will advance quickly.  If high risk he recommends treatment, and patients should consider an open clinical trial for treatment. 

Dr. San Miguel's work is what I believe will be the first step required to make myeloma a disease which is Found Early, Followed to when it becomes HRSMM, and Fought with a treatment regimen with a goal of CURE.  So let's F Myeloma, Find, Follow, and Fight it. 

Good luck and may God Bless your Cancer Journey.   For more information on multiple myeloma survival rates and treatments CLICK HERE and you can follow me on twitter at: https://twitter.com/grpetersen1






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    Gary R. Petersen
    [email protected]
    CLICK HERE for my myeloma journey

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