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October 2000 Volume 4, Issue 1:
Myeloma Today Profile: Professor Régis Battaile
Dr. Battaile is a Professor of Hematology at the University of Nantes and Head of the central laboratory of hematology at the University Hospital
Myeloma Today: Please tell us a little about yourself. Where did you go to medical school and how did you become interested in myeloma?

Prof. Bataille: I went to the Medical School of Clermont-Ferrand in the center of France. Then I moved to the Univer-sity of Montpellier for my internship. I worked for 15 years as a medical doctor at the University Hospital in the Department of Immunology and Rheumatology. In 1991, I moved to the University of Nantes as a Professor of Hematology, Head of the central laboratory of hematology at the University Hospital. This is my current status. 

I became interested in multiple myeloma at the beginning of my internship in 1972. My M.D. and Ph.D.
theses were devoted to the clinical and biological features of multiple myeloma respectively. My interest in multiple myeloma was strengthened during my early stays in Tucson at the University of Arizona, when I worked with Sydney E. Salmon and Brian G.M. Durie. My first works were published with them. 

At the present time, besides the central laboratory of hematology, I coordinate a myeloma research group involved in basic research. Senior scientists, experts of myeloma, are presently working full-time on the molecular and cellular biology of myeloma: M. Amiot (CNRS1), S. Barille (INSERM2), S. Minvielle (CNRS) C. Pellat Deceunynck (CNRS) and H. Avet-Loiseau (Univ. Hospital). This research is performed in close collaboration with J.L. Harousseau and his colleagues in the Department of Clinical Hematology in Nantes. A lot of patients with myeloma are directly referred to this department. Prof. Harousseau, myself and our colleagues are very active in the work of the IFM3, our national myeloma study group and in the development of its clinical trials. The central laboratory of Nantes is the laboratory of reference for the IFM and collects all myeloma samples for FISH and molecular studies.

MT: You've had a special interest in myeloma bone disease. Is that still a major area of your research? If so, what is the most exciting research into the causes and treatment of bone disease?

Prof. Bataille: Myeloma bone disease remains a major area of our research. This topic is more particularly studied by one of our senior scientists, S. Barille (Inserm). With regard to the causes of myeloma bone disease, our most interesting data show the potential involvement of an imbalance between OPG ligand (a potent osteoclast differentiation factor) and OPG (its natural inhibitor in the occurrence of bone disease). Myeloma cells induce this imbalance through their interactions with bone cells. These data could have some interest to develop new therapeutic strategies. OPG could be used to inhibit OPG-L. Disruption of myeloma-bone cell interactions with specific antibodies could also be planned. Bisphosphonates, especially new bisphosphonates, are also of major interest for us. We are more particularly interested in the potential anti-myeloma effects of some of them.

IL-6 has also been of interest for you. Can you update us on this area of research and why you feel it's important? 

Prof. Bataille: We continue to work a lot on the role of IL-6 and its soluble receptor in the pathogenesis of myeloma. As it is confirmed in mice, in humans the IL-6/SIL-6R complex play a major role in the occurrence, survival and expansion of malignant plasma cells through transcription factors like stat-3 and anti-apoptotic molecules like BCL-2, BCL-XL, MCL-1... In our group, this topic is more particularly studied by M. Amiot (CNRS). We believe that targeting these factors and molecules represent interesting therapeutical strategies. In a Phase II study, we have shown that anti-IL-6 treatment significantly improved the efficiency of steroids and high dose melphalan. We have recently carried out a randomized study within the IFM to confirm these data. Furthermore, we plan to investigate anti-IL-6 receptor and BCL-2 antisense.

MT: IFM is often in the news and referred to at major research conferences. What it so unique? What are the major initiatives that have earned IFM recognition and what new studies are in the works?

Prof. Bataille: It is clear that IFM is now a major myeloma study group. Please note that IFM is not simply a French group any more, since teams from Belgium and Switzerland joined us. I think that the strength of IFM is its capacity to quickly recruit many new myeloma patients. (In France, there are about 2,000 patients diagnosed with myeloma every year.) IFM can also count on the quality of participating centers and the competence of its myeloma experts (M. Attal, T. Facon, H. Avet- Loiseau, B. Grosbois, J.J. Sotto, J.L. Harousseau, and myself). Finally, IFM can count on some research labs working on myeloma, such as those in Nantes. Thus, IFM is now supported by the French Ministry of Health. Many new studies are in the works about tandem transplants, bisphosphonates, thalidomide, mini-allo transplants, and anti-IL-6 strategies.

MT: What areas of research do you see as the most important with the advent of sophisticated molecular technology? Do you foresee new molecular treatment strategies for myeloma emerging soon?

Prof. Bataille: I think that the use of DNA chips and the definition of myeloma chips are very promising. The discovery of new genes involved in the biology of myeloma, including tumor antigens could allow definition of new targets for chemotherapy and immunotherapy. In our group, three senior scientists (H. Avet-Loiseau, S. Minvielle and C. Pellat-Deceunynck) are working on that. More recently, our lab has been selected to coordinate a national project on this topic. 

MT: As you know, the National Cancer Institute will be conducting a Progress Review Group for myeloma. If you were to make recommendations for new areas of research, what would they be? Are there any areas that you feel are no longer relevant? Do you see international collaboration as helpful in making progress?

Prof. Bataille: Obviously, I will recommend all the previous emphasized topics, each of them being promising. However, there are some other very interesting topics like myeloma induced angiogenesis and the development of new anti-angiogenic drugs. In the same way, all the new approaches in immunotherapy are very exciting. It is always difficult to say that some areas of research are not relevant anymore. I can only say that some areas of research have been disappointing until now (e.g. MDR, interferon) but this could change. I think that for the future, the biology and management of MGUS and smoldering myeloma have to represent a major area of research. MGUS allows access to the early steps of myeloma oncogenesis and to early diagnosis of myeloma. International collaboration could be helpful in different domains – sharing adequate biological tools, sharing rare events in a single center (such as transition from MGUS to myeloma), sharing knowledge about clinical trials in the works to avoid redundancy and save money, etc.

MT: For patients coping with myeloma, what treatments or new therapies do you see as offering the most hope?

Prof. Bataille:
As detailed previously, there are now several new therapies to be evaluated. To help save time and money and, more importantly, to be efficient and effective in attaining our goals, the efforts of myeloma experts, NCI, national governments, and myeloma foundations should be coordinated. Myeloma foundations could support specific roundtables and workshops to accelerate the process.

MT: This is the 10th Anniversary for the IMF. You've been a part of the foundation for many years. What accomplishments of the IMF are you most proud of? Do you see the IMF taking a more active role in France? The IMF plus the IFM could be a very formidable coalition - do you agree?

Prof. Bataille: I think that the best accomplishments of the IMF were its fast organization to collect money, help patients and researchers, especially in the USA. I think that everybody would be pleased if IMF was more active in France to support IFM clinical trials and/or basic research. Recently, I discussed with IMF the idea of supporting “myeloma centers” for 3 or 4 years rather than single projects. I think that this could be an interesting point. 

MT: Any final comments of thoughts you would like to share with our readers?

Prof. Bataille: I have been working on myeloma for more than 25 years. I have managed many patients. Today, for the first time, I am optimistic for the future.

1. CNRS (Centre National de la Recherche Scientifique) 
manages the overall scientific research, including Life Sciences;

2. INSERM (Institut National de la Santé et de la Recherche Médicale) is the French equivalent of the NIH;

3. IFM (Intergroupe Francophone du Myélome) is a Myeloma Study Group 
that include more than 100 medical centers from France, Belgium and Switzerland. 

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