As an avid follower of Google alerts for multiple myeloma and a reader of all things multiple myeloma on the Internet, a recent article caught my attention.

“Novel Therapies Put Multiple Myeloma on the Ropes” read the headline from the Oncology Report Digital Network.

The article led off with the statement “A sweep of new agents are poised to deliver what could be a knockout blow to multiple myeloma."

It then quoted Dr. Jeffrey Wolf, the director of the multiple myeloma program at the University of California, San Francisco, saying "We have made such tremendous headway in myeloma, except for those exceptional cases with ... adverse prognostic features."

"As a disease," Dr. Wolf added, "[multiple myeloma] seems to be on the ropes.”

Hum, really?  After seeing this article, I knew I wanted to write about this as it related to my own experience and situation, but it has taken a little while to get my mind around it.

The article goes on to describe some of the new novel agents in the pipeline, many of which we have been hearing about and were reported on by The Myeloma Beacon from the recent American Society of Hematology annual meeting. Carfilzomib ^[1] (Kyprolis ^[2]), the new proteasome inhibitor cousin to Velcade ^[3] (bortezomib); pomalidomide ^[4], the third generation of thalidomide ^[5] (Thalomid) and Revlimid ^[6] (lenalidomide); the histone  deacetylase inhibitors Zolinza ^[7] (vorinostat) and panobinostat ^[8]; the monoclonal antibody elotuzumab ^[9]; and others were all mentioned.

Don’t get me wrong, this is all exciting stuff and it’s great to see the amount of work being done.

But let’s be clear. In reading the results carefully, most of these developments seem to represent incre­mental changes at best.  I’m just not sure we are at the point of “on the ropes.”

I do think some clearer distinctions need to be made.

First of all, there is no question that the outlook for multiple myeloma patients has improved greatly over the last 10 years.  The use of novel agents has helped double survival during that period.

It seems the picture is especially good for patients who are diagnosed now.  Multiple drug combinations of novel agents, stem cell transplants, the trend towards pushing for better complete responses even after transplant and maintenance therapy do truly seem to be changing the landscape.  When and if these patients relapse, the drugs will only be better.

But what about patients who are further along in the treatment? People who have been treated with Velcade, thalidomide, and Revlimid and who are relapsing now?

The path is far from clear.  That is my situation now.

It has been almost six years since my diagnosis.  At various times during the course of treatment for multiple relapses, I have been on Revlimid, thalidomide, Velcade, and several combinations of these.  I have tried pomalidomide in a clinical trial.

All of these drugs worked for a period of time and have allowed me good quality of life during that time.

One year ago, after a bad relapse, I underwent a salvage second stem cell transplant, which I had written about in an earlier post.

Initially, the results were very good.  However, after about 10 months on maintenance therapy with thalido­mide and Velcade following the transplant, my M spike started going up again and I am now back in full relapse mode.

So now what?  As I said, the path becomes much muddier.

As I and others have said before, there are no right or wrong answers; however, I am not even sure there are any good answers.

Certainly, all the investigational drugs mentioned are available through clinical trials.  But even that is not that simple.

First of all, certain clinical trials are available only through certain treatment centers.  I am, of course, more than willing to go anywhere if it would help.

Secondly, many clinical trials involve randomization.  That means that even if you do travel for the clinical trial, you may wind up being randomized to the ‘standard of care’ arm of the trial and not receive the new drug, at least not initially.  Definitely not an option in my situation.

Most importantly, in heavily treated, Velcade- and Revlimid-refractory patients, most of these drugs seem to only be effective in about 20 percent to 30 percent of patients at best.  Additionally, the responses are not necessarily very long.

Carfilzomib, for example, which is available through an expanded access program called C-MAP until FDA approval, is only effective in about 20 percent of Velcade-refractory patients. Better than nothing, but I sure would be hoping for better odds than that.

Furthermore, under the C-MAP program, carfilzomib cannot be combined with any other drugs except dexamethasone ^[10] (Decadron).   There are some carfilzomib trials combining it with other drugs, but which one is no better than a roll of the dice.

As another example, Zolinza plus Velcade in Velcade-refractory patients worked in 11 percent of the patients.  Not very impressive.

I have what I feel are two of the best myeloma specialists in the country, Dr. Melissa Alsina at the Moffitt Cancer Center and Dr. Ken Anderson at the Dana-Farber Cancer Center, and they do not even seem to be sold on the next great idea.

After some discussion between them, the decision was to put me on a combination of the old drug cyclophosphamide ^[11] (Cytoxan), which is being revived in multiple myeloma; Velcade; and dexamethasone, abbreviated as CyBorD ^[12].

The decision was based on the need to do something quickly because of the rapid rise in my M spike and the fact that I had taken cyclophosphamide before my salvage stem cell transplant last year with a good response.

Unfortunately, this regimen was of no help.

So that’s where we are right now. The next step is inpatient chemotherapy again.

Right now, I’m feeling more like multiple myeloma has me on the ropes than the other way around.