Book Review

Myeloma: Biology and management

N Engl J Med 1995; 333:672-673September 7, 1995

Article

Myeloma: Biology and management
Edited by James S. Malpas, Daniel E. Bergsagel, and Robert A. Kyle. 581 pp. New York, Oxford University Press, 1995. $98. ISBN: 0-19-262480-6

The study of multiple myeloma has fascinated and challenged a multitude of workers in basic science and clinical medicine. Nevertheless, progress in treating this disease has been slow. The cause is unknown, and because the ancestral myeloma cell is unknown, biologic and molecular aspects of the disease are difficult to study. A major consequence of our ignorance is that therapeutic advances have been minimal.

Indeed, when I entered medical school in 1967, the sixth and last single-authored edition of Maxwell M. Wintrobe's Clinical Hematology (Philadelphia: Lea and Febiger) stated that the cause of multiple myeloma was unknown. As for treatment, melphalan held the greatest promise, cyclophosphamide induced a substantial number of remissions, and prednisone was useful when these agents failed. There was no evidence that the administration of immune globulin was helpful for a complicating infection. In 1974, the seventh edition stated that the cause of plasma-cell dyscrasias was “obscure,” melphalan and cyclophosphamide still held great promise, and intermittent high doses of prednisone were a useful alternative. Immune globulin therapy was ineffective, and the median survival was 24 to 50 months.

Few would be more qualified than Drs. Malpas, Bergsagel, and Kyle, leaders in myeloma research, to edit a book on multiple myeloma. Their multiauthored textbook consists of four sections, “Pathophysiology,” “Clinical Features,” “Therapy of Myeloma,” and “other Disorders Associated with Paraproteinaemia.” There are adequate numbers of clear and simple figures and tables. The book provides a traditional description of the structure and function of immunoglobulins, the development of normal antibody-secreting cells, and the process by which molecular lesions may lead to malignant transformation. The importance of cytokines, notably interleukin-6, and their receptors in regulating cellular proliferation is an interesting story. It has been evolving in recent years and now has therapeutic implications. The chapter on molecular biology is brief (13 pages) as compared with that on morphology (42 pages) and does not adequately discuss the contribution of apoptosis to the pathogenesis of myeloma. The thorough chapter on epidemiology is an excellent review, but unfortunately epidemiologic studies of myeloma have been unable to draw consistent conclusions.

The chapter on prognostic factors suggests that myeloablative treatment is the preferred alternative for high-risk patients; however, the literature indicates that only low-risk patients, if any, benefit from this procedure. Dr. Bergsagel's thorough presentation of chemotherapy and interferon therapy points out the frustrations of physicians who treat patients with myeloma. The various multiagent regimens have no major advantages over melphalan and prednisone; few treatments are more effective for second-line therapy than high doses of steroids; and the median survival remains 24 to 50 months. Clinicians will find Bergsagel's chapter to be a useful guide to management. The chapter on bone marrow transplantation provides a balanced view of a highly controversial subject and is one of the standouts of the book.

The chapters on radiotherapy, hematologic abnormalities (primarily anemia), the renal and calcium-related disorders, and the psychosocial aspects of myeloma will interest physicians working in those specialties. A notable omission is a chapter on infectious complications, their causes and management, and the controversies surrounding treatment with intravenous immune globulins and hematopoietic growth factors. The book concludes with well-written chapters on monoclonal gammopathy of undetermined significance, plasmacytoma, amyloidosis, heavy chain disease, and Waldenström's macroglobulinemia.

Most who open this book with the intention of reading it in its entirety will find it too formidable; neither is it intended as a source of guidance for future research. On the other hand, it is an excellent compendium for those interested in hematologic cancers in general and multiple myeloma in particular. Perhaps sufficient progress will be made toward characterizing the malignant cell in myeloma and manipulating the biology of that cell to therapeutic benefit to merit an expanded section in the next edition.

Bruce D. Cheson, M.D.
National Cancer Institute, Bethesda, MD 20892