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August 2000 Volume 3, Issue 10:
Myeloma Today Profile
Professor Hakan Mellstedt
Myeloma Today: Prof. Mellstedt, please tell us where you did your training and how you became interested in myeloma?

Prof. Mellstedt: I had my training at the Karolinska Institute in Stockholm, Sweden. I received my M.D. degree in 1969 and completed my Ph.D. thesis in 1974. The thesis was on myeloma and was also done at the Karolinska Institute. I also have a certificate in internal medicine, and hematology and oncology. In 1969, Raymond Alexanian published his report on treatment of myeloma using melphalan and prednisone and I was asked to introduce this regimen at the University Hospital at Karolinska Institute. I was just starting my career – I didn’t even have my certificate yet. I became interested in myeloma. The head physician of the department was a tumor immunologist and we realized that a lot of the immunology studies could be done in myeloma.

MT: The Karolinska Institute is a highly regarded center. Please tell us about it.

Prof. Mellstedt: The Karolinska Institute is an umbrella organization for all medical education in Stockholm with a medical faculty of its own. There is a campus with mainly pre-clinical research and there are two large university hospitals, the Karolinska Hospital and the Huddinge Hospital, which are the clinical research facilities of the Karolinska Institute.

MT: You have a particular interest in immune regulated myeloma growth. How did you become interested in this area, why do you think it’s important and what is the latest progress?

Prof. Mellstedt: I am a tumor immunologist who started doing immunological studies in myeloma. My main interest has always been immunology in myeloma. I was the first to describe the existence of precursor myeloma B cells – a report published in 1974. I soon realized that there was a unique structure on the surface of the myeloma cell that could be utilized as a target for therapy. At that time, I was not really aware of T cell regulation. As we acquired more knowledge in immunology, we realized that T cells could regulate the growth of tumor cells. I realized that there might be a specific regulation of the tumor clone in myeloma. At the end of the 1970s, I was the first to describe abnormalities in T cells in myeloma. I didn’t know how, but the T cell population was in some way connected to the disease. In the 1980s, we acquired more information on T cell function. Were there specific T cells that could spontaneously recognize the tumor clone in myeloma? There were several reports of this in animal (mouse) models. At that time I was the only one who worked with T cells in myeloma in humans. We demonstrated that there were specific T cells that could recognize the tumor cells. An attractive hypothesis was that this might regulate growth, that the human immune system could spontaneously recognize myeloma cells and a vaccination approach could be successful. We were the first to recognize idiotype reactive T cells but we didn’t yet know in detail what these cells did with regard to regulation of the tumor clone. Since then, we have developed a lot of technologies for therapy but we have not been fully successful. At present, we might be able to cure some patients with myeloma but I’m not quite sure of this yet. We can induce complete remission but the disease comes back. And gene therapy treatment has no effect. We have to develop other treatment modalities.

We are very interested in early stage myeloma. Such patients will develop myeloma, even if it takes a long time, and that means you should not give them chemotherapy regimens, which are toxic. If we could find non-toxic regimens, then we could start treatment very early and prevent progression. Here, vaccination might have a role. Developing vaccination strategies in early disease is what we are aiming at. I think that this approach is most favorable because during the early stage of the disease, the immune system is comparatively well preserved. The immune system is compromised by the progression of the disease and by chemotherapy and transplantation. It becomes extremely depressed. Theoretically, it should be more likely to have effective immunity induced early during the disease.

MT: You were one of the first to investigate the role of interferon. Is it still an important part of myeloma therapy?

Prof. Mellstedt: Interferon has a statistically proven effect in myeloma but the gain in survival is maybe 4 to 6 months. I developed interferon therapy at the end of the 1970s and at that time there was no other effective treatment. Since then, there has been great progress in developing different therapies and interferon has become less important. In medicine, there is constant progress whereby old therapies are replaced by new ones.

MT: The progression from MGUS to active myeloma is different in Scandinavia than elsewhere. Can you explain this?

Prof. Mellstedt: This has to do with the health care community in Sweden. Patients tend to see their doctors more often and we are more likely to detect MGUS early. Therefore, we have a broader knowledge of prevalence of MGUS in our society. It is more a reflection of the diligence of the Swedish health care system in general.

MT: You recently hosted the VII International Myeloma Workshop. You were also an attendee at the first Workshop held. How has this meeting changed over the years? Do you feel that Tim McElwain's original intent is still being carried out?

Prof. Mellstedt: At the first Workshop, there was a select group of approximately 40 doctors with a very devoted interest in myeloma research. Now we have 800 attendees who are interested in learning about the disease but are not necessarily actively involved in myeloma research. Mostly, they are hematologists and oncologists interested in acquiring knowledge. Clearly, the format has changed. At the first meeting, highly knowledgeable individuals gathered around a table to have very constructive open discussions about myeloma. This cannot be done with 800 participants. Both meeting formats are very important but their goals cannot be the same.

MT: What are the goals of the myeloma group you have established at the Karolinska Institute?

Prof. Mellstedt: We have two myeloma groups at the Karolinska Institute. We have a Myeloma Group of Central Sweden – a large group of 9 to 10 hospitals in the Stockholm area collaborating on different treatment protocols. Then there is my research group, with 12 to 15 people dedicated to myeloma research. Our goal is to study immune biology, especially with regard to T cell function in myeloma, and to develop a vaccination strategy for myeloma.

MT: What do you see as the most hopeful area of research for patients coping with myeloma today?

Prof. Mellstedt: Currently, developing immunotherapies is one of the important strategies. We know much more about tumor immunology compared with 10 years ago. We have information from various other tumor systems about how a vaccination strategy might be developed. In myeloma patients, you have spontaneous T cell immunity and I think there is a good hope of developing a clinically effective vaccination strategy. We have excellent results from animal models, and the resources and the background are in our hands.

MT: The IMF has been awarding research grants since 1994. This year, you were one of the recipients of a Senior Grant. What has this award enabled you to do?

Prof. Mellstedt: With the help of the IMF award, we have been able to develop a position in the laboratory entirely devoted to studying T cells. In studying myeloma, it is important to understand how T cells function at the general level. We know that cancer patients, including those with myeloma, have various defects in T cell function and this is one of the reasons why vaccination strategy might fail. We are the first group – maybe the only group at the moment – trying to characterize in detail and understand in general T cell immune dysfunction in myeloma. When we have a good overview of this, we might be able to enhance immunity by vaccination. There are two options: we can select patients who are more likely to respond to treatment because of their well-preserved T cell function and, I believe, we will soon have drugs which might reverse T cell dysfunction that can be added to the vaccination protocol. Then we will have the possibility of inducing more effective immunity. The IMF grant has enabled me to enlarge my research group with a highly competent person entirely devoted to this research.

MT: What do you see as the major role of the IMF in the myeloma community?

Prof. Mellstedt: IMF has a definite role in the myeloma community. Raising awareness of the disease is a very important goal, not only among physicians and patients, but also others. The IMF has done very well in this area. The IMF also raises funds to increase the capacity of myeloma reseach – money that only goes to study this disease.

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