It’s been said over and over that multiple myeloma encompasses a wide spectrum of diseases.

It includes people with the precursor diseases monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. It also includes newly diagnosed patients with active myeloma, those approaching their first stem cell transplant, some patients who are fairly stable on maintenance therapy, and those progressing after various treatments.

I think the different phases of the disease are reflected well by the diverse perspectives of the contributors to The Myeloma Beacon. I, too, have writ­ten over the years about my experiences at various stages of the dis­ease.

I am finding myself at a different stage now.

I have high-risk, relapsed, refractory disease that has progressed through treatment with all available stan­dard therapies, including two autologous (own) stem cell transplants and an allogeneic (donor) transplant.

It’s multiple myeloma on the far end of the spectrum.  I know I am not alone.  There are many others like me.  Having blown through transplants, chemotherapy, novel agents such as thalidomide ^[1] (Thalomid), Revlimid ^[2] (lenalidomide), and Velcade ^[3] (bortezomib) and now Kyprolis ^[4] (carfilzomib) and Pomalyst ^[5] (pomalidomide, Im­no­vid) in all sorts of combinations, the disease marches on.

Like many others, I’m not ready to through in the towel.  But where to turn to next?

We are inundated with the latest new drugs, advances, and “breakthoughs.”  Many of the new drugs are only available through clinical trials, which have confining inclusion and exclusion criteria that have ruled me out.

Some of the new drugs are variations of drugs we have seen. We also hear of highly touted new therapies in the popular media, yet they are actually too far off to be of use now.

I have been on something of a fact-finding mission recently to try to sort all of this out.

Through research, emails, phone calls, and doctor visits, I’ve tried to explore myeloma on the edge.

I’m not trying to find pie-in-sky ideas and solutions that are far down the road.  Instead, I'm searching for practical, immediately actionable solutions for my specific situation.  I’m currently on an individual patient protocol with elotuzumab ^[6], Revlimid, cyclophosphamide ^[7] (Cytoxan), and dexamethasone ^[8] (Decadron) which, for now, doesn’t seem to be working.

Thus, I’m actively looking for my next option.

Here are the observations that I have made in my search.

First of all, while there is a lot of information and options out there, it is not always easy to sort through them in a meaningful, orderly way.

Second, even your own doctor may not have all the information or be in a position to evaluate all the options.  Doctors have widely differing opinions, perspectives, and approaches in treating a disease.

I hate to say it, but not all doctors are equal.  To be blunt, some are better than others. Some tend to be more conservative, waiting for evidence to accumulate before embarking on a certain therapy.  That’s okay, but you have to recognize that approach.  I, on the other hand, am looking for the thought leaders -- the progressive, out-of-the-box thinkers.

In the process of reviewing potential options, I was also reminded of some important points that I some­times lose sight of.

One of them is to not to be too quick to start a new therapy.  Try to get as much mileage as you can out of a treatment regimen before switching.

In addition, everything doesn’t have to be a home run.  Even a treatment with which I can achieve stable dis­ease for a few months has value for me at this point.

From the standpoint of specific treatments, while there is overlap, I found it helpful to break the available therapies into four basic categories: traditional chemotherapy, novel agents, immunotherapy, and genomics.

Traditional chemotherapy includes options such as VTD-PACE, DCEP, and others. The University of Ar­kan­sas uses a protocol of a slow continuous infusion of chemotherapy over a 30-day course.

Traditional chemotherapy has in many ways been a very successful therapy for me.  At least for now, my disease still responds to it. I have been told by some that traditional chemotherapy is my best and only realistic route of treatment.

The problem is that the results are not long lasting. The only end game seems to be either slow de­te­ri­or­a­tion of my disease or some bad complication.

Immunotherapy seems to be one of the hottest areas of research right now and might very well hold the most promise.  Engineered T-cell trials being developed at places like the University of Pennsylvania, Ohio State, and the University of Maryland look like really exciting treatment options. Some of these options are available now through clinical trials.

Unfortunately for me, on drilling down, I found that immunotherapy protocols such as these – and most other ones – exclude allo transplant patients like me, at least for now.  I nevertheless think that these trials might be excellent treatment options for some patients.

Genomics was a hot buzzword, but it seems as though enthusiasm for it has waned a little. Genomics in­volves testing a sample of a patient’s tumor for specific genetic mutations and then using a drug known to tar­get that mutation to treat the patient.  The problem is that this approach is turning out to be very complex, and there are not too many drugs immediately available now (except for some of the repurposed melanoma drugs), and the responses to the treatments seem to be pretty short lived.

All of this brings me back to the novel agents. There are literally dozens of novel agents out there in various stages of clinical trials.

So how do I narrow the choices? I have specific criteria I am looking for when choosing a drug.

I need drugs that have a different mechanism of action than the ones I have taken before. I could be wrong, but it is hard to get very excited about a third-generation proteasome inhibitor. I also need drugs that have good activity against my type of aggressive, fast-growing disease.

Finally, I need a drug that is available through either a clinical trial without randomization and without in­clu­sion and exclusion criteria that would keep me out, or through compassionate use, single-patient pro­to­cols.

While all the details have not been worked out yet, the most promising drugs I have come across are a couple we have all heard about – the monoclonal antibodies daratumab ^[9] and SAR650984 ^[10] – and two we have not heard as much about yet, selinexor (KPT-330) and filanesib ^[11] (ARRY-520).

I have always been as cautious and skeptical as anyone one about breakthroughs on the multiple myeloma front.

Perhaps it’s just wishful thinking on my part, but I am encouraged that it really feels like significant progress is being made.  Options are available, but they are not always obvious and have to be actively sought.

Whether they will work is another matter.