Chapter 07: Myeloma: Breakthroughs with Transplant Supported Chemotherapy

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Chapter 07: Myeloma: Breakthroughs with Transplant Supported Chemotherapy

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Dr. Alexanian discusses the transplant supported program in myeloma. He sketches the history of the program and the rationale of the treatment: administering extremely high doses of melphalan and then "rescuing" the patient from toxicity with stem cell transplants, a procedure resulting in 25 - 30% complete remission lasting four years. He explains how willing patients were to participate in these studies and he describes his interactions with patients as he explained procedures. Dr. Alexanian next talks about the challenges of obtaining insurance coverage for experimental therapies. He then goes on to note that this chemo-transplant procedure is still the standard of treatment for some patients. Dr. Alexanian then explains how Dr. Barlogie left MD Anderson.

Identifier

Alexanian_R_01_20140415_S07

Publication Date

4-15-2014

Publisher

The University of Texas MD Anderson Cancer Center

City

Houston, Texas

Topics Covered

The Interview Subject's Story - The Researcher; The Researcher; The Clinician; Discovery and Success; Patients; Professional Practice; The Professional at Work; Collaborations; Multi-disciplinary Approaches; Fiscal Realities in Healthcare

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

Disciplines

History of Science, Technology, and Medicine | Oncology | Oral History

Transcript

Raymond Alexanian, MD:

Anyway, but also that doctor-the major influence then, the next thing was when Dr. Barlogie joined me. Dr. Barlogie was a very important scientist who worked in Dr. Freireich's department in the laboratory, but he was also interested in clinical matters and was a very inspiring person to work with, who thought of a number of imaginative things and felt that if we could exploit a-there was an Englishman named McElvain, M-c-E-l-v-a-i-n, who presented a paper that showed that if you gave Melphalan in very high dose, very high toxic dose, severely toxic doses, you could recontrol the myeloma in patients who would otherwise be dying of myeloma, but with a high mortality of about 25, 30 percent. So Dr. Barlogie said, "There's something there that we need to look into."And I said, "Great."So he said, "Why don't we just see if we can use the high doses and rescue the patient with a transplant so they would survive the procedure."So he then persuaded our transplant service. The gentleman's name I'm thinking is from Holland. Why can't I think of his name? So we decided, "Okay, let's find some patients who would otherwise be dead in a few months, and let's do the same procedure on them."So I said, "Well, you can't do it on them, because their marrow is filled with tumor, and how are you going to get your stem cells?"Remember stem cells, that's my old field. (laughs)

Tacey A. Rosolowski, Ph.D:

Mm-hmm.

Raymond Alexanian, MD:

"How are you going to get your stem cells?"So I said, "Well, maybe there are enough in there that we can use, or maybe we can work out a way of purifying it or something like that."Well, to make a long story short, there were enough even in patients-enough stem cells.

Tacey A. Rosolowski, Ph.D:

Oh, really?

Raymond Alexanian, MD:

But at the time you drew the marrow, then there weren't enough in everybody. In other words, you couldn't tell who had enough stem cells to save them and who didn't. So we could collect the marrow, calculate if we had enough, give them the high-dose therapy, give them their marrow back, and hope for the best.

Tacey A. Rosolowski, Ph.D:

My god.

Raymond Alexanian, MD:

They're otherwise dying, though, so they sign consents.

Tacey A. Rosolowski, Ph.D:

Sure.

Raymond Alexanian, MD:

So it turned out that more than 90 percent had enough stem cells, but in the early phases, we did lose a small number because what we thought were sufficient were not, and it turned out to be effective in half of the 90, half of those. In other words, we were able to do what McElvain had done without the transplant with the transplant and pull 90 percent of them through it successfully. So then it was apparent pretty early on that even though it worked, it only worked for a few months, six months. So I said, "Well, this doesn't make sense. We've got to do this earlier in the disease, before they relapse."So then we said we have to take patients who are in remission, who are healthy and not relapsing, and who could be healthy for five years, and then take their stem cells, hope we had enough, and hit them hard then. Of course, no one had done these things before. (laughs)

Tacey A. Rosolowski, Ph.D:

Right, right.

Raymond Alexanian, MD:

So then we started to do that, and it turned out that we began to see instead of what we call partial remissions, which is where you have remission but you still have residual disease left, from the tests that we do, we began to see a higher number of so-called complete remissions, there was no sign of disease, that we rarely ever saw with just Melphalan and Prednisone. Melphalan and Prednisone may have a 5 percent complete remission rate, but with the transplant-supportive therapy, it had become 25 percent or 30 percent. So I said, "Something's happening here, and maybe that'll last longer."Well, it does last. Complete remissions do last a lot longer, but then there was, again, recurrence.

Tacey A. Rosolowski, Ph.D:

How long did those remissions last?

Raymond Alexanian, MD:

Partial remissions lasted, on the average, two years, and complete remissions lasted, on the average, four years.

Tacey A. Rosolowski, Ph.D:

Now, let me ask a question. Here you have a patient who's in remission, they've gone through, you know, a very arduous treatment process. Was it difficult to convince patients to undertake another trial, to go through this kind of thing again? Raymond Alexanian, PhD Well, one of the things about a center like this, which, even before the patient comes here, has a big, strong reputation, and when they've come to see a specialist in that center such as myself, who has probably a lot more experience than their oncologist does in this disease, and I explain to them that, "This is where we are in our knowledge of your disease and that your likelihood of relapse is such-and-such after so many years, based on previous natural history."As I mentioned, every patient I see is a study, so I'm collecting all of this, hundreds and hundreds of patients in my database, that I can tell them with some accuracy, "This is what's going to happen if we don't do this with certain ranges, you know. And we're developing this new program, which involves this, this, and so on, and I can tell you, sir, that if it were me or my family, I would do it, because we have maybe done it ten and you may be the eleventh, and so far it's working out and they're getting through it. It's not easy, and you don't have to do this if you don't want to, but I think it's worth it. Plus it's going to cost you a lot,"because insurance had not approved these procedures, "but we can cover some of it at a center like ours."It's curious, we can cover the indigents, but we can't cover those with money. You know that.

Tacey A. Rosolowski, Ph.D:

Mm-hmm, mm-hmm.

Raymond Alexanian, MD:

So the indigents who come here get more-in those times, got more expert professional attention than those with resources, because they couldn't afford it, which is a sort of, I guess, kind of an irony, you might say. However, very quickly on, we lobbied hard to get Medicare approval, and then once they got Medicare approval, we got insurance approval, and this took a couple of years.

Tacey A. Rosolowski, Ph.D:

What years are we talking about here for this process?

Raymond Alexanian, MD:

Oh, gosh, I'd have to look at my-can I see this?

Tacey A. Rosolowski, Ph.D:

Yeah, sure. Let's see. I didn't have a date for those bone marrow transplants. I hadn't done a complete review of your-

Raymond Alexanian, MD:

I would say in the 1980s, somewhere in there. And Dr. Barlogie was very instrumental in working this out too.

Tacey A. Rosolowski, Ph.D:

Oh, really.

Raymond Alexanian, MD:

So then it's become the standard of treatment now so that-

Tacey A. Rosolowski, Ph.D:

And it's still the standard treatment?

Raymond Alexanian, MD:

Standard treatment.

Tacey A. Rosolowski, Ph.D:

Wow.

Raymond Alexanian, MD:

However, only about 80 percent of patients qualify for it. There are certain physical health requirements. You can't have severe heart disease or emphysema, and the transplant service likes to have people who are fit-looking. By that they mean if they can at least walk to the bathroom. And there are some patients who come from abroad who are unable to stay or you have to be physically here. So about 20 percent who might qualify don't receive that for various reasons, but almost all of them do, 80 percent. Then there were more complexities. [unclear] says, "Well, if one transplant is good, maybe two transplants are better."And that's what Dr. Barlogie developed when he moved to Arkansas. So the people who I work with always move on somewhere else, right?

Tacey A. Rosolowski, Ph.D:

Why did Dr. Barlogie leave?

Raymond Alexanian, MD:

He wanted to set up a Myeloma Center, which-I think he could have stayed here, and I begged him to stay and try to do it here, but I don't know the full-are you going to interview him some day?

Tacey A. Rosolowski, Ph.D:

I don't know. I haven't heard his name before, so I don't know.

Raymond Alexanian, MD:

Well, the University of Arkansas were willing to commit huge resources, a whole building, staff, money, multimillions, to develop a Myeloma Center in Arkansas. So it is called the Myeloma Cancer Center, and you could look up his résumé. It's very impressive.

Tacey A. Rosolowski, Ph.D:

Interesting.

Raymond Alexanian, MD:

And it turns out that his Center was so successful that he had some conflict with his Division of Medicine head, who wanted some of the money drained to his services that were coming into the Myeloma Center.

Tacey A. Rosolowski, Ph.D:

Very interesting.

Raymond Alexanian, MD:

So that's the reason he moved.

Chapter 07: Myeloma: Breakthroughs with Transplant Supported Chemotherapy

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