Multiple myeloma remains an incurable disease, but advances in medicine are clearly improving patients’ outlook. Increasingly, doctors are speaking of remissions lasting many years and even of the possibility of a functional cure for some patients. Hematologists stress that access to modern therapies is crucial — both in first-line treatment and in the event of relapse.
“Treating myeloma is relatively complex. This is because it is an incurable disease and, by definition, requires multiple lines of therapy. Even after using the best possible first-line treatment, we must plan for further therapy in the event that it fails. This happens in most cases, so second-line treatment is then used, followed by third- and fourth-line options. The complexity of these treatment lines makes therapy relatively difficult both for the physician and for the patient,” Prof. Dominik Dytfeld, MD, PhD, President of the Polish Myeloma Consortium, said in an interview with Newseria.
Multiple myeloma is a cancer of the blood-forming system that originates in plasma cells in the bone marrow. The disease leads, among other things, to bone damage, anemia, immune disorders, and kidney failure. In Poland, around 9,000 to 10,000 people are living with multiple myeloma, and several thousand new cases are diagnosed each year. The disease mainly affects older people, with the median age at diagnosis being around 70.
“Despite the use of the most effective first-line therapy, remission can be achieved in most patients, and it often lasts for several years. Unfortunately, the disease biologically adapts to these conditions and over time becomes resistant to previously used treatment. When that happens, another line of therapy becomes necessary,” Prof. Dominik Dytfeld explains.
At the beginning of the 21st century, patient outcomes were far worse than they are today. Progress in treatment is mainly linked to the introduction of new classes of drugs, including proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. The use of multidrug therapies has made it possible to achieve deeper treatment responses and extend the duration of remission. As a result, average survival time has increased significantly.
“When I began working in the early 2000s, a patient with myeloma lived for two to three years. Now we are talking about the prospect of a functional cure, and survival may be measured in fifteen to twenty years. That is something extraordinary,” says the President of the Polish Myeloma Consortium.
Progress in treatment also results from the introduction of new drug combinations targeting different mechanisms of the disease. In recent years, four-drug regimens have played an increasingly important role, allowing for a deeper treatment response already in first-line therapy. Clinical studies indicate that this approach may significantly extend the duration of remission.
Complex therapeutic regimens based on several drugs acting on different disease mechanisms are playing an increasingly important role in the treatment of myeloma. They make it possible to control the disease more effectively and prolong the time to progression. This approach is currently one of the main directions in the development of hematological therapies, although access to the latest treatment regimens is not equal in all countries.
In the near future, new therapeutic regimens may be added to the drug program both in first-line treatment and in the management of relapsed disease. Clinical trials are increasingly using multidrug regimens that allow for deeper and longer remissions.
“Myeloma is a disease that is becoming a chronic condition before our eyes. Thanks to the introduction of new therapeutics in new combinations, we can speak not only about extending the time to subsequent progression, but also about prolonging patients’ total overall survival. We are also beginning, very cautiously, to say that perhaps some patients whose treatment will begin in the near future may be functionally cured,” says Prof. Krzysztof Giannopoulos, President of the Polish Society of Hematologists and Transfusiologists.
The development of more effective first-line therapies means that new mechanisms of drug action are needed in subsequent stages of treatment. In the case of relapse, it is often no longer possible to repeat previously used therapeutic regimens. That is why one of the key directions of research is the development of new targeted therapies that act on different biological mechanisms in cancer cells.
“In the case of relapse, we also need to use even more effective drugs, because if four-drug therapies are used in the first line, in most cases we cannot repeat them. We therefore need to look for new drugs, and ideally not one or two, but three drugs,” explains Prof. Krzysztof Giannopoulos.
One of the new therapeutic options being developed for relapsed multiple myeloma is belantamab mafodotin, an antibody-drug conjugate directed against the BCMA antigen present on myeloma cells. The drug works by delivering a cytotoxic molecule directly to the cancer cell. This approach makes it possible to increase treatment effectiveness while limiting the impact on healthy cells.
In clinical trials, the response rate to belantamab treatment was 30–35%, including in patients previously heavily treated with multiple lines of therapy. In phase III trials, belantamab-based combination regimens showed a significant extension of progression-free survival compared with standard three-drug regimens.
“Belantamab is also a very modern molecule that includes a monoclonal antibody, meaning a molecule directed against an antigen on the surface of the cancer cell. We already have such drugs, but we do not yet have a drug that contains a cellular toxin in its structure — and that is exactly what belantamab is. This design increases anti-cancer effectiveness,” emphasizes Prof. Dominik Dytfeld.
Belantamab mafodotin belongs to the group of so-called antibody-drug conjugates (ADCs). This therapy involves combining a monoclonal antibody with a cytotoxic molecule which, after binding to the cancer cell, is delivered into it and leads to its destruction. In clinical trials, treatment regimens using this drug demonstrated higher effectiveness than some of the therapies previously used in relapsed myeloma.
“These are, in fact, the three technologies that are most lacking today: stronger first-line therapies, belantamab in the second line, and CAR-T therapy,” lists the President of the Polish Myeloma Consortium.
CAR-T therapies are among the most advanced treatment methods currently being developed in hematology. They involve the use of a patient’s T lymphocytes, which, after genetic modification, are able to recognize and destroy cancer cells. In Europe, two CAR-T therapies are currently approved for the treatment of relapsed multiple myeloma. They are used primarily in patients whose disease has returned after many previous lines of treatment.
