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By Marty Vanderlaan

Photo by: Dennis Schrader Photography | http://dennisschraderphoto.com

In previous blogs in this series I have described getting Rituxan for a rare non-Hodgkin’s Lymphoma variant known as Waldenstrom macroglobulinemia (WM). My manifestation of WM is complicated by light chain amyloidosis. In this case, my tumor cells (lymphoplasmacitic lymphoma [LPL] cells) produce a free immunoglobulin lamda light chain which precipitates in organ-destroying amyloid fibrils, and while damage to my critical organs has not yet occurred, that may only be a matter of time.  

Concurrently with the 18 weeks of Rituxan therapy (6 x 3 week intervals), I received weekly injections of Velcade, and oral dexamethasone and cyclophosphamide. Velcade has the potential to be a very appropriate therapy for those with amyloid disease because it targets the proteasome. In amyloidosis, the lamda light chains that precipitate are believed to be misfolded, denatured, or otherwise defective.  As such, they would be targets for removal by the cell proteasome before they ever are secreted.  Blocking the proteasome protein disposal pathway should “choke” the cells. Overall I tolerated this treatment well. There were injection site reactions that persisted for several weeks, and with weekly injections I was beginning to feel a bit like a pincushion.

The biggest systemic reaction to this combination of treatments was muscular soreness. One night I was convinced both kidneys were failing because of the sharp pain in my lower back. But rolling my back on a styrofoam cylinder rapidly reduced the pain and relaxed my back muscles. I recommend treating yourself to a professional massage on a regular basis while undergoing this kind of therapy.getting-rituxan

Another huge help was being taken to treatment by my network of friends. We used the lotsahelpinghands website to organize my support. This website allows one to schedule friends to offer services, like transportation or meals, and allows the patient to send out periodic announcements to their community, like health updates. Community support is essential for cancer therapy patients.

I, however, was only a partial responder to these treatments. My lung tumor dissipated and my lung function returned. I gradually was able to resume exercising and now routinely walk 5 miles a day. My hemoglobin level rose. Flow cytometry showed no peripheral blood B-cells or plasma cells. But, a bone marrow biopsy showed 5% WM cells remained, and my serum IgM and free light chain levels were not reduced.

At this point, I was started on ibrutinib, an inhibitor of Bruton’s tyrosine kinase (BTK). BTK is a key intermediate enzyme in the survival and activation of B-lymphocytes. WM patients usually have a genetic mutation in the MyD88 gene that leads to a constant state of “on” for survival signals (failure of normal apoptosis) which can be blocked by BTK inhibitors. While ibrutinib comes with a long list of potential side effects, the only one I have had is an occasional deep bone ache, which I hope reflects it killing the residual tumor cells in my marrow.

However, after 16 weeks on ibrutinib, my IgM level is only down by a factor of two (to 14 g/L) and my free lamda light chain is unchanged at (0.156 g/L). I have to wonder if I am really responding to ibrutinib.

The alternative therapy at this point is an autologous bone marrow stem cell transplant (ASCT). This is a formidable undertaking, but perhaps better undertaken now while my organs are not damaged by amyloid deposits, and I am otherwise fit. The promise is that ASCT is a “reset” on my bone marrow, as close to a cure as is available. The disadvantage is the risk of infection and slow recovery of one’s immune system once it has been completely ablated and must regenerate from stem cells. One goes back to being completely immunologically naive, and must receive all of one’s childhood immunizations again, for example.

Another option is to wait for a new therapy to come along. The field of cancer therapy is moving so rapidly that it is possible that within a year or two there will be other options. So, I will give ibrutinib a few more months to see if the serum markers improve, before making this decision.

Martin Vanderlaan, Ph.D. Analytical Chemist/Toxicologist from NYU Medical School. Recently retired after 20 years at Genentech, where he held a number of lab director positions, including head of Analytical Chemistry and Operations in the Process Development organization.