I took off from writing my column in January while under­going treat­ment and try­ing to sort through other treatment options.

Since my donor (allogeneic) stem cell transplant in August 2012, my multiple myeloma had recurred again with aggressive extramedullary disease (myeloma outside of the blood and bone marrow).

This progression occurred despite several cycles of a regimen of Kyprolis ^[1] (car­filzomib), Pomalyst ^[2] (pomalidomide, Imnovid), cyclophosphamide ^[3] (Cy­toxan), and dexamethasone ^[4] (Decadron), leaving me in a very bad situ­a­tion.

Fortunately, my disease responded to a couple of cycles of high-dose chemotherapy with Velcade ^[5] (bortezomib), thalidomide ^[6] (Thalomid), and dexa­methasone plus cisplatin, doxo­rubicin ^[7] (Adriamycin), cyclophosphamide, and etoposide (known as VTD-PACE).

The question now is what to do next?

I have exhausted all of the standard approved multiple myeloma drugs many times over.  What does a multiple myeloma patient do when all conventional treatments have failed?

Since I do respond, at least for now, to more traditional high-dose chemotherapy, some type of “main­te­nance chemo” regimen has been discussed; I am not sure what that would look like yet, though.

Another option is off label use of a drug currently approved for other cancers.  There are a few drugs ap­proved for other cancers that may be effective in multiple myeloma.

For example, based on genetic testing, a small percentage of multiple myeloma patients have the BRAF mu­tation found in malignant melanoma and may respond to a drug currently approved for that cancer. I have had the genetic testing done, but that’s a whole other discussion.

The other obvious option is an investigational drug.  By far the easiest way to get access to an investi­ga­tion­al drug is to enter into a clinical trial.

There are a few problems with that from my standpoint.

The main one is that all clinical trials have specific inclusion and exclusion criteria.  My specific cir­cum­stances – particularly my having had a donor transplant and having nonsecretory disease – exclude me from almost all trials.

The potential to be randomized to receive treatment not including the investigational drug, and the inflexibility to combine the investigational drug with other drugs not included in the study, are other problems.

Whenever I write a column like this, people always respond with suggestions about what to try.  It’s not that I don’t appreciate it, but, believe me, I’ve looked.  I don’t think there is too much out there that I haven’t re­searched or looked into.

The other option for obtaining an investigational drug outside of a clinical trial is through a program called “compassionate use.”  There is no Dallas Buyers Club for unapproved multiple myeloma drugs that I know of.

First a little background.

In 1938, the U.S. Food and Drug Administration (FDA) was given the authority to oversee the safety of drugs in this country and to prevent unapproved drugs from entering interstate commerce. Under FDA regulations, drug companies must obtain approval for any investigational new drug before beginning human testing.  The company must tightly limit and monitor patients who use the drug, usually under a clinical trial.

Over the last two decades, the FDA has allowed companies under certain circumstances to expand access to investigational drugs to individual patients outside a clinical trial through the “compassionate use exemption.”

The patient’s doctor must apply to the drug company for the drug and agree to monitor its use.

The patient must have advance disease, have failed standard treatment, not be eligible for a clinical trial, have no other treatment options, and have some expectation of the drug working with the benefits out­weigh­ing the risks.

Sounds like me.

There are few important things to know about getting a compassionate use exemption.  First, it is a long, sometimes daunting, process. Most importantly, and often misunderstood, is that this is not primarily an FDA decision.  It is up to the individual drug company to decide if they want to allow access through compassionate use.  They have no obligation to do so. The FDA cannot compel them to do so.  If the company agrees to make their drug available for compassionate use, the FDA approval in reasonable circumstances is fairly routine.

There are several reasons the drug company may not approve compassionate use.  There may be limited drug supply.  They can be concerned about compassionate use taking patients away from clinical trials. The drugs may be used in less-controlled settings on sicker patients, setting them up for more side effects be­ing reported.  The company does not gain much useful information.  The data from compassionate use is not included when going for FDA approval, but any side effects have to be tracked and reported.  So in fact, it is often not in the company’s best interest to allow compassionate use.

We decided to apply for compassionate use of elotuzumab ^[8].  It’s fairly far along in clinical testing.  As a mono­clonal antibody, it’s a completely different category of drugs than anything I have been on. Combined with other myeloma drugs, elotuzumab is showing some good, durable responses.  Elotuzumab is likely to be the next multiple myeloma drug approved by the FDA, but that could be a year or two off.

My doctor sent the appropriate paperwork to the maker of elotuzumab, Bristol-Myers Squibb (BMS).  It took over two months to get an answer: “The senior medical group of BMS met to review compassionate use of elotuzumab.  New compassionate use requests will not be considered at this time.”

Denied! Are you kidding me? The thing to understand is that compassionate use is not necessarily about compassion.  These are carefully calculated business decisions being made by the drug companies.

BMS is getting ready to go for FDA approval for elotuzumab and does not need any reports of new side effects.

So now what?  One more last ditch appeal? More chemo? Other drugs through compassionate use? Using genomic testing information?

I am exploring all options and not giving up yet.

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Update (Feb 14, 2014) - After The Beacon published the above column, the Beacon staff contacted Bristol-Myers Squibb to make it aware of the column and to see if it wished to make any statement in regard to it. A BMS representative responded, saying that the company does not comment on individual patient cases, but that it did have the following statement:

Bristol-Myers Squibb is committed to developing medicines in areas of high unmet medical need. In many cases, our medicines are being studied as potential treatments for patients with limited to no viable treatment options. It is exactly with these patients in mind that, through regulatory approval, we work to ensure broad access to our medicines as quickly as possible, while also remaining mindful of protecting patient safety.

In the long term, the best way to ensure the broadest access for patients is to successfully register a medicine with health authorities through the conduct of well-controlled clinical trials.

In certain cases, Bristol-Myers Squibb has offered investigational medicines in late stage development to healthcare providers for the treatment of patients outside of clinical trials, after evaluating the degree of unmet medical need, the availability of other treatment options, and the extent of available safety and efficacy data on the compound at the appropriate dose.

We empathize with patients who have limited treatment options and are committed to establishing the benefit / risk profile of elotuzumab as quickly as possible. Our Phase 3 program for elotuzumab is on­going and we are closely collaborating with health authorities.