Multiple myeloma, an insidious form of bone marrow cancer, has lost an important battle. New drugs are now showing an effect where no help was available just a short time ago and up to 90% of myeloma patients stand to benefit.
"Twenty years ago only 40% of our patients responded to our therapy. Now we have a range of drugs that are effective individually or in combination in more than 90 percent of the people treated," says Professor Heinz Ludwig, director of the First Medical Department for Oncology and Hematology at Wilhelminenspital, a major hospital in Vienna, Austria. "Patients who could no longer be helped by any other means were able to get back out of bed with these new drugs and lead a normal life. That takes us a big step closer to getting the once so feared multiple myeloma under control."
Professor Ludwig is the President of the 2007 Congress of the European Hematology Association, yet another event with which Vienna confirms its reputation as the leading conference city on the continent. No fewer than 7.000 experts in blood and bone marrow diseases will be gathering at this event to share new findings.
Among the various advances in treatment being presented at this mega conference, the one on multiple myeloma is probably the most impressive. Well into the 1950s, this form of bone marrow cancer was untreatable and resulted in death within a few months. Then suitable cortisone and chemotherapeutic preparations began to show the first effects ever against myeloma cells. Another major step forward came with the development of autologous bone marrow transplantation, i.e. transplanting the patient's own healthy bone marrow cells back into the patient. Yet dramatic improvements in the situation for patients first began in very recent years, with the introduction of drugs that attack both the myeloma cells and the bone marrow environment that promotes tumor growth.
Insidious mechanism
Myeloma is referred to as "multiple" because its foci often form concurrently at several places in the skeleton. The initial steps of malignant transformation occur in B-lymphocytes, the precursors of plasma cells, which are capable of forming antibodies against viruses, bacteria and other microorganisms, and thus constitute an essential element of the adaptive ("learning") immune system. Myeloma cells produce only a single type of identical ("monoclonal") antibodies instead of the usual broad range of antibodies needed. These identical antibodies are known as paraproteins, and in 15 to 20 % of the cases, only fractions of these proteins are formed, so-called "light chains".
These paraproteins are often generated in large numbers resulting in high protein concentrations and sometimes even in symptoms from hyperproteinamia. Multiple myeloma also involves a shift in the balance between bone-building and bone-destroying stem cells in favor of the latter, called "osteoclasts" causing an decrease in bone density (osteoporosis) and frequently also in the formation of osteolytic bone lesions or bone fractures. Patients with excessive production of light chains are at risk of renal dysfunction, because these paraproteins can severely damage cells of the renal filter system.
Intelligent modes of action against cancer
Professor Ludwig: "In the active ingredient Bortezomib, we now have a substance that can kill off malignant plasma cells with a completely new mode of action. It inhibits the degeneration of important regulatory proteins in cancer cells, thus preventing signals that stimulate cell growth. Bortezomib also inhibits vascular growth, repair mechanisms in tumors and the interaction of tumor cells with their environment. Moreover, this drug is the only one that promotes the rebuilding of bony tissue."
The second therapeutic milestone is called lenalidomid. Professor Ludwig: "This substance belongs to a new class of what are referred to as immunomodulating drugs. They are relatively small molecules with a number of different modes of action operating simultaneously. Among other effects, they inhibit inflammation, retard the spread of degenerated cells in the body and prevent the formation of blood vessels important to tumor growth."
Complete disappearance of tumor cells for up to 40% of the patients
Multiple myeloma is not yet curable with these methods, but it can be brought largely into remission. Unfortunately, the risk of reoccurrence continues to prevail. All the same, enormous progress has been made. The survival period of earlier times was a matter of one to three years. Now median survival after stem cell transplantation may reach 5 to 6 years, with about 20% of patients being still in remissions 10 years after initial therapy. Earlier generations of drugs were capable of temporarily bringing about a nearly complete disappearance of the symptoms of this disease, a symptom-free state, in only five percent of the patients. The potent methods of today's hematologists do so in an average of 30% of patients and in certain constellations, in an astounding 44%.
Present advances by no means signal the end of the horizon. "More than 80 new drugs are now being developed to treat multiple myeloma. Of this total, more than 30 are already being tried in clinical trials on patients," noted Professor Heinz Ludwig. "We can certainly look forward to further major advances."
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