While the discussion below offers no profound "solution" for those with multiple myeloma, it does offer a good discussion of medical alternatives and potential new drug treatments for this form of blood cancer.  It is also a good discussion for anyone having a friend or family member with this disease to get a better understanding of treatment options.

The major problem with what is being discussed below is that there is no mention of the cost of the drugs.  Because MM is relatively rare - about 18,000 new diagnosis per year, the big pharmaceuticals have not had a financial incentive to pursue drugs for it.  I am to begin my treatment in another few weeks and one of the options I've been given is a relatively new drug which costs $1,000 for 28 (one cycle) pills.  My insurance will pay about $800 of that which still leaves me paying a hefty prescription bill.  If I don't choose that option it means that I have to go in on a weekly basis for infusions which Medicare will pay.  

For MM there are no easy alternatives.

http://www.medpagetoday.com/clinical-context/MultipleMyeloma/31653?utm_conten...

Multiple Myeloma: Relapsed and Refractory Patients, a Clinical Context Report

By Michael Smith, North American Correspondent, MedPage Today

Published: March 18, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

Transcript:

SMITH: I'm Michael Smith of MedPage Today, and I'm here with Dr. Stan Gerson, Director of the Seidman Cancer Center at University Hospitals Case Medical Center in Cleveland. Dr. Gerson, welcome to MedPage.

GERSON: Thank you.

SMITH: We're going to talk today a little bit about multiple myeloma and, in particular, a tough group of patients, those with relapsed or refractory disease -- the difficulties of choosing appropriate therapies for those people, some of the complications that they might run into, and then some of the new drugs coming down the pipeline. It's an interesting time in multiple myeloma because there have been a number of new agents and there are a number of combinations available, but let's begin by talking about the kinds of challenges, disease-related, regimen-related, and patient-related. What sorts of things must a clinician be aware of, I guess?

GERSON: Well, everyone with myeloma will relapse, and everyone with myeloma will end up with some sort of level of refractory disease. Even patients who go through a stem cell transplant often will relapse, so this is a very common issue. Many of the issues in the management relate to the age of the patient, how much therapy they've had and how much they can take, the types of complications they have -- in addition to the diagnosis of being relapsed -- and what they have received before. On the other hand, the optimism is that, for almost all of those patients, there's always a treatment that can be delivered.

SMITH: And that's actually a relatively new thing. We've had a number of agents come down the pike in the last eight to 10 years, that in some sense have changed the face of multiple myeloma. There's thalidomide, bortezomib, and lenalidomide, which is of course a thalidomide variant. Tell me about those. What do we know about those drugs? What sorts of results can they deliver?

GERSON: Well, they are just phenomenal. There's about a 40% response rate with any one of the individual drugs. That response rate is improved simply by taking one of the chemotherapy drugs that you've described and adding a steroid, such as dexamethasone, and then adding combinations increases the response rates to 50, 60, 70, or even 80%. So the initial response rate is terrific. What's really interesting about myeloma is that, even at relapse, these patients will respond to the other agents. Sometimes they'll even respond to the initial agent that was given.

SMITH: That's fascinating. So what you're saying is that if I, for instance, have multiple myeloma and I fail a course of treatment with one of the thalidomide derivatives, I can go to another one; I don't burn the class.

GERSON: That's absolutely correct. And so, very meaningful responses can be observed for years in patients who go from thalidomide to lenalidomide, for instance.

SMITH: It used to be that the treatment was largely chemotherapeutic. What's happening with chemo? Is that being used at all now or what's the state of play?

GERSON: Well of course. Myeloma had been managed with melphalan, and melphalan alone or melphalan with vincristine, and those drugs are still useful, not as first-line, because these other agents are actually more effective. But when there's a difficult time, using and reconsidering the use of melphalan and vincristine is important. On the other hand, there's a drug called bendamustine, which was originally developed and is actually used and approved for use in CLL [chronic lymphocytic leukemia], and now can be used in relapse of myeloma. A number of studies have shown 30, 40, 50% response rates, again in clinical trials, with the use of bendamustine.

SMITH: So chemo is not off the table either.

GERSON: No it isn't.

SMITH: A lot of drug options for patients. What about the old standby? If people have failed therapy, presumably someone who had tried a transplant, can transplants be done again?

GERSON: It's pretty rare for us to consider double transplants. On the other hand, I've just taken a patient through who had a transplant in 2003, and she just went through a second autologous transplant, and now we are eight years later. And so, the answer is yes, and so we don't want to use transplant in the active phase of disease. We want to make sure people have a good response first, and then when, if you will, minimal disease is left, then consider a stem cell transplant.

SMITH: And the other question I think that arises is there are all of these agents and quite often, agents are used in combination. Is that becoming the standard approach in multiple myeloma?

GERSON: Most patients are receiving two or three drugs upfront and two or three drugs at relapse. After a transplant, maintenance is very commonly used now just with a single drug at much lower doses and, in fact, it's pretty rare for us to tell a patient with myeloma that the best thing is observation. We typically keep them on treatment for a prolonged period of time. There are often cases, however, in which a person with active myeloma will enter a more subdued phase and may stay in that subdued phase for an extended period of time.

SMITH: What about now, obviously, if people are on treatment for long periods of time and they still have active disease, there are likely to be treatment-related side effects and disease complications. What are the most common ones? This is probably a huge list, but what are the most common such events and how would you manage them?

GERSON: About a year ago, a publication came out showing the equivalency of using bortezomib, which is a newer agent, a proteasome inhibitor, either alone or in combination, and, instead of intravenously, using it subcutaneously. And the biggest difference was a marked reduction in the amount of neurotoxicity. Older individuals often have neurologic problems anyway. They develop peripheral neuropathy from either thalidomide, lenalidomide, or from bortezomib, and using the subcutaneous bortezomib is very effective at reducing that very significant clinical side effect. That's the most significant one of all that we have. Of course there's infection issues, which are very important, and so prophylaxis with antibiotics is critical in this population, often forgotten, but is absolutely critical, especially in combination and in patients who are receiving high doses of steroids.

SMITH: I see. The big question, I guess, is what can we look for in the future. I went online just earlier today and I looked for what kinds of agents are coming down the list, and I've got a paragraph here that's about three lines long; monoclonal antibodies, agents targeting mTOR, a whole range of them. Where are those in the process? Are we going to see some of those in the clinic soon?

GERSON: Well, I think in fact the most important message is actually that patients at that point in their treatment decisions really should be considered for a clinical trial, because it's important for us to evaluate. Some of these agents are going to be dramatic in their response, most likely in a small proportion of patients, because we know that there are such important pathways that regulate the disease. The problem with testing them late in the course of the disease is that patients with myeloma will develop multiple components of their resistance profile, and any new drug is unlikely to be that good. So we're likely to see, with these newer agents, 20, 25%, very significant responses, which is why a patient should participate in clinical trials, until we figure out how to combine them with agents much earlier in the course of treatment.

SMITH: And many of these drugs of course, are still in the phase I, II stage.

GERSON: Phase I and phase II, and they're going to have trouble getting out, because again, we have so many drugs coming up early, that most of the patients considered will be multiply relapsed.

SMITH: Right. That said, there are a couple that are fairly close to approval. There's another thalidomide variant, and I'm going to try and pronounce this, pomalidomide.

GERSON: Well, pomalidomide is actually very impressive to me because it's in the same class as lenalidomide and the parent compound if you will, so it's very similar to a drug called thalidomide, and those three drugs can be used sequentially with still having very good responses, and it teaches us a little bit that the drugs aren't really quite as identical as some other derivative drugs are in the chemotherapy world. But in this world, where they modulate the types of proteins that are produced and cytokines that are produced, they can be still very effective, and so there's some dramatic responses to pomalidomide for instance.

SMITH: And another one coming down is a small molecule and again, carfilzomib.

GERSON: So that drug has just been reviewed by the FDA, and so we're going to hear very soon, about the place that it will have. It will mostly likely come out as a drug that can be used for relapsed myeloma. And again, it has shown some very good responses in patients who didn't have many other options. It doesn't have that high response rate, but in that setting we need another drug.

SMITH: Right. And of course if people have failed multiple drugs, the more you have the better. Give me -- just characterize, just as we wrap up here -- characterize how a patient should feel if he or she is in this patient population of relapsed or refractory multiple myeloma. Optimistic, resigned?

GERSON: There are plenty of opportunities. Very few people are dying without an opportunity still left in the armamentarium of their physician with myeloma. So typically, patients have age-related problems or infections or other things, rather than having raging myeloma. So there are many, many treatment options and there are times when I'll come around and re-use a drug that I've used three, four, five, or eight years ago, and still find that the patient can be effectively treated. So there are many, many options, many more than there were even four or five years ago.

SMITH: So a good time if you have to have multiple myeloma.

GERSON: If you have to have myeloma, you're doing better than you did a decade ago, that's for sure.

SMITH: Great. Thank you very much for your time Dr. Gerson.

GERSON: Thank you Michael.

SMITH: I'm Michael Smith, MedPage Today.