Challenges of Non-Secretory MM

The popular anti-Multiple Myeloma agent Bortezomib (Velcade) has just won FDA approval for subcutaneous injection. This means that it can be administered as a simple injection versus intravenous (IV) infusion. Velcade and it’s subsequent analogs work by being protein inhibitors. Abnormal proteins are a byproduct typical of Multiple Myeloma. However, I have to ask what value it might have for patients like myself. I’m what’s called a non-secretor, which means that my Multiple Myeloma doesn’t manifest any of the proteins common to the cancer. As such, it wasn’t a big surprise (in hindsight) that while I suffered the side effects of extreme fatigue and profound peripheral and systemic neuropathy, I took no benefit at all from the multiple cycles of Velcade prescribed by my oncologist. I’m not only in the tiniest category of Multiple Myeloma, I’m also a part of the component of patients whose side effect manifestations were as severe as they come. Non-secretors tend to suffer from neuralgia more quickly and severely.

What’s even worse, I am also sensitive to steroids, which help prepare the body to more effectively use the toxins employed in treatment. It causes a tremendous increase in heart rate and blood pressure, placing me at severe risk of stroke and cardiac issues. Any treatment considered for me has to forego the use of steroids, which drastically increases the likelihood I’d present the side effects of any of the anti-cancer agents, and that presentation would be more severe. This was proven true when the use of Doxorubicin produced both toxic shock and anaphylactic shock that was nearly fatal. Doxorubicin is a class of compound called anthracyclines and they work by binding to DNA and changing its construction, causing it to kill both healthy cells  and cancer cells. However, it is attracted to cells that are highly active, and so it kills more cancer cells than healthy. In my case, the balance wasn’t as prejudiced in ratio and attacked so many healthy cells the result was nearly fatal. This is what prompted the swing to Velcade as an alternative.

However, it would have been a better choice to switch me over to Thalidomide or Lenalidomide (Revlimid). The mechanism by which Thalidomide and its analogs works is actually a mystery. However, it is a known agent that slows bone cancers, likely by reducing the production of new blood vessels. It is believed that the reduction of vessel manufacture slows the production of cancerous areas, particularly tumors, and thereby slows the advance of the cancer. Thalidomide is also an immunotherapy, bolstering the body’s immune system which also benefits the body’s own protective mechanisms. Contrary to some opinion, Thalidomide does not kill cancer cells as Doxorubicin does, nor does it have the anti-protein mechanisms of Bortezomib.

Hindsight is 20/20 as the expression goes. Once affected severely by neuropathy, a pathway is set for a faster return to the exquisite agonies it produces. When I was finally changed to a regimen of Lenalidomide, it took less than a cycle for the disabling level of neuropathy to return, causing the abandonment of all treatment. In my case, the treatment was infinitely worse than the cancer. While my reaction to Doxorubicin was unexpected, still, my oncologist, a hematologist of 40 years experience, was right to suggest it. For a non-secretor, it was a good first line treatment. Had the next step been a reach to Revlimid to retard the cancer growth, I might have fared better. But I was agreeable to the use of Velcade because I understood that prevailing wisdom, then and now, says to treat Multiple Myeloma and non-secretory Multiple Myeloma the same way, with the same tools.

Non-secretor Multiple Myeloma victims constitute only 1% of those afflicted with the cancer. We tend to survive longer and because our cancer progression is slowed and we do not suffer the affectations of proteins damaging our kidneys and other organs. However, we are much more likely to suffer neurological issues afforded by treatment, and to a greatly higher degree. My own case stands testament to this assertion. My body tolerated Velcade well, showing little adverse effect, save for peripheral neuropathy. I lost the use of my feet and my hands at the peak of its manifestation. Attempts to use Gabapentin (Neurontin) to reduce the PHN was unsuccessful and I suffered the effects of the neuralgia full on. Only a small percentage of peripheral neuropathy sufferers gain benefit from Gabapentin and its ilk.

Sufferers of non-secretory Multiple Myeloma can be a bit more relaxed in their approach to therapy. With the slower progression and lack of collateral affect, more time is offered for the development of a treatment strategy. Using this time is wise, because once neurological complications arise, their return will be more immediate in subsequent treatment attempts. It is common at diagnosis for non-secretors to be staged higher than standard Multiple Myeloma victims. On diagnosis I was at stage three, the highest. This is because the lack of proteins permitted the cancer to grow to a great degree unnoticed. For us, it takes a lot longer to begin experiencing the symptoms which usually cause people to seek medical help. I thought I suffered a bad back because the pain created by the cancer was in my lumbar area, exactly where most people suffer back strain. I also suffered from chest pain, but only occasionally, and doctors I brought it up to attributed the discomfort to stresses because there was no real evidence of cancer to be found. Non-secretory Multiple Myeloma is only detectable through the damage it does to bone, seen via PET scan; with the best confirmation of its presence being bone marrow inspection, produced by aspiration or biopsy, sadly a very painful methodology. However, it will reveal the presence of Multiple Myeloma undeniably.

Non-secretors present a greater difficulty in diagnosis and treatment, and they’re more likely to suffer side effects most severely. This makes us a greater challenge to the medical community to diagnose our cancer, and equally difficult to treat us.