Chapter 08: A Breakthrough Myeloma Treatment with Thalidomide

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Chapter 08: A Breakthrough Myeloma Treatment with Thalidomide

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Description

In this chapter, Dr. Alexanian talks about the treatments he innovated using thalidomide. He explains that thalidomide can inhibit angiogenesis, and Dr. Barlogie used it on dying patients with good results. Dr. Alexanian explains that he was looking at the next step: to use thalidomide in combination with Velcade and dexamethasone, supported by stem cell transplantation. He notes that over forty years of working with drug combinations, the treatment of myeloma at MD Anderson has gone from no remissions to remissions that last an average of six years. He also notes that he has been following patient for twenty years and there are some who have not relapsed in twelve years.

Identifier

Alexanian_R_01_20140415_S08

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; Collaborations; Multi-disciplinary Approaches; MD Anderson and Government; Critical Perspectives on MD Anderson

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:

+ So anyway, but still we carried on here. It turns out that the double transplants were not any better than the single transplant. Then the notion was, well, how about giving a double transplant with the first transplant your own cells and the second transplant from a matched sibling donor, so you can get a graft versus tumor effect. There are all kinds of variations on that, and that didn't turn out to be successful. CLIP Research Successes The next big breakthrough came with the two drugs, the Thalidomide group of drugs and the Velcade or Bortezomib group. Now, you should probably read a little bit on how Thalidomide became discovered. Have you heard of that?

Tacey A. Rosolowski, Ph.D:

Tell the story for the record. (laughs)

Raymond Alexanian, MD:

Dr. Barlogie had a patient who was otherwise dying and wanted to offer a new drug to try something on him, so he asked a specialist in-let's see. What is the research area? And I can't remember his name either. Oh, my memory. Anyway, a specialist at Harvard who was doing work related to small-capillary development around tumors, and he found that Thalidomide, which is a drug that caused birth defects, could inhibit the development of this vascular network, and why don't you give it a try? Of course, Thalidomide had become an orphan drug, but it was still available through sources in Europe and other places, and it was available because it was effective in treating a group of patients with HIV who got various skin ulcers, and I cannot recall the details of that, but it was an effective drug in healing. So Dr. Barlogie gave a patient Thalidomide. It didn't work in the first one, and he gave it to a next one. One of these first two patients had-there was an article in New York Times about the evolution. I should bring that clipping to you, because it was such an interesting journalistic story. The wife of the patient begged him to try anything on her husband, and so he found the Thalidomide and gave it, and I don't know if it was to her husband or the next patient, it was effective in controlling the myeloma-

Tacey A. Rosolowski, Ph.D:

Wow.

Raymond Alexanian, MD:

-just out of the blue. And a whole new development of Thalidomide and analogs of Thalidomide developed, and there were very rigorous controls in terms of avoiding pregnancy and so on. So the Celgene company, that was virtually nonexistent and operating out of a closet, you might say, sort of had manufactured this for the HIV patients and became a huge profit-making company because of this single drug and other drugs to follow and then-

Tacey A. Rosolowski, Ph.D:

So were there difficulties with dosage? I mean, how-were you involved in this as well?

Raymond Alexanian, MD:

So once it was effective, I said, "Well, what do we do next?" We put it in combinations, right?

Tacey A. Rosolowski, Ph.D:

Yeah, yeah. Right. Mm-hmm.

Raymond Alexanian, MD:

So, therefore, we were first to do a combination of-I forget the first combination, Thalidomide with Dexamethasone, and somewhere in here Dr. Weber has a paper on that. Then the next drug that came was Valcade that Dr. Orlowski was instrumental, who is now head of myeloma, developed when he was at North Carolina, and this drug was also, as it was being evaluated in Phase 1 trials in cancer, different cancers, found to be effective in myeloma, one patient or two patients, and says, "Oop, we got another one." So, the next round of combinations. So the current standard of care is a combination of Velcade first with Thalidomide and Dexamethasone, and then with its analog, R_____ and Dexamethasone, followed by transplant. So that over a period of forty years we have evolved from no remissions and an average survival of a year and a half in myeloma to a combination of drugs that can control and transplant that induces remission in 95 percent of patients, of whom 40 percent are complete remissions and where the average survival is six years, median survival, with about 3 percent probably being cured. I have a paper on curability in here, the last paper-

Tacey A. Rosolowski, Ph.D:

Mm-hmm. That's the most recent one.

Raymond Alexanian, MD:

-where we followed patients for up to twenty years. This is from the old file, carried on, that about 3 percent of patients have not relapsed. They're in complete remission beyond twelve years. In other words, between twelve and twenty years, still in complete remission.

Chapter 08: A Breakthrough Myeloma Treatment with Thalidomide

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