Truth or Myth? CAR-T treatments are changing the fate of multiple myeloma patients

For years, multiple myeloma was considered a chronic disease that could only be controlled, not cured. In recent years, biological drugs, innovative immunotherapy treatments, and CAR-T technology, which recruits the patient's immune system to fight cancer cells, have been added to the treatment basket. Even when the disease returns after treatment, patients now have options that did not exist in the past. The results do not guarantee a cure for every patient, but they mark a turning point: for the first time, the medical community is speaking cautiously, but explicitly, about the potential for a cure in some patients.

Against the backdrop of these changes, Professor Yael Cohen, Director of the Myeloma Unit at the Tel Aviv–Sourasky Medical Center (Ichilov) and Chair of the Israeli Myeloma Group, sorts out myths from facts and explains which perceptions about the disease no longer stand the test of reality.

Myth 1: Myeloma is an incurable disease

Not true. Professor Cohen:

"For many years, multiple myeloma was defined as an incurable disease. In fact, almost every professional article about the disease began with this sentence. If in the past we almost never used the term 'cure' in the context of myeloma, today it is already part of the scientific discourse. We see deep and prolonged responses in some patients that were not observed before, and therefore for the first time it is possible to speak cautiously about the potential for a cure in some patients. As we continue to integrate innovative treatments at earlier stages of the disease, we estimate that this potential will continue to grow."

Myth 2: If the disease has returned after treatment, there is nothing more to do

Not true. Professor Cohen:

"Disease recurrence is part of the expected course of myeloma for many patients, but it is definitely not the end of the road. In recent years, new treatment options have been added that allow for control of the disease even after several lines of therapy. Among the advanced approaches are bispecific antibodies, which connect T-cells of the immune system to myeloma cells, and CAR-T treatments, in which the patient's immune cells undergo modification and are engineered in the laboratory so that they can identify and attack cancer cells. This is a change that we see as dramatic. The earlier advanced treatments like CAR-T are given in the early stages of the disease, the deeper and more prolonged responses we see — a finding that strengthens the hope that we will be able to expand the number of patients who will enjoy long-term remission in the future. But even in advanced stages of the disease, studies have shown that the treatment led to a high response rate, with over 90% of patients achieving a response to treatment. Today, there are patients who remain without any evidence of disease activity even after three and even five years of follow-up after CAR-T treatment. These data allow us to hope that a one-time treatment may lead to a cure in some patients."

Myth 3: Multiple myeloma is a disease that attacks only elderly people

Not true. Professor Cohen:

"Multiple myeloma is more common in older age. The median age at diagnosis is about 70 years, meaning half of the patients are younger than this age and half are older. However, it is definitely not a disease of the elderly only. We also meet patients in their 40s and 50s. Therefore, it is important to be aware of the symptoms and not rule out the possibility of myeloma just because of age, as even at a relatively young age, early diagnosis can affect further treatment."

Myth 4: Unlike other oncological diseases, there is no personalized treatment for myeloma

Not true. Professor Cohen:

"Of course, we adapt the treatment to the characteristics of the patient himself, for example, age and background diseases, but when we talk about personalized medicine, we mainly mean adapting the treatment to the biological characteristics of the myeloma in each patient. Personalized medicine is one of the main directions in the development of myeloma treatment, and it is expressed on several levels. The most prominent example is CAR-T treatment. This is a one-time treatment in which T-cells collected from the patient's blood are used, undergo genetic engineering in the laboratory so that they can identify myeloma cells and destroy them, and are then returned to the patient's body. This is a treatment that is produced individually for each patient. In addition, today we know how to identify genetic changes and biological characteristics of the disease in some patients that may affect the choice of treatment. There are also genetic tests that allow us to assess the risk level of the disease and its degree of aggressiveness, and accordingly adapt the intensity of treatment already at the early stages. Another area that is developing rapidly is the in-depth characterization of myeloma cells and the immune system of each patient. In our laboratory, for example, we study the biological characteristics of myeloma cells and the state of the immune system to understand which treatments or combinations of treatments will be most effective for each patient. The better we understand the biology of the disease, the more accurately and informedly we can adapt the treatment for each person."

Myth 5: For patients whose disease progresses quickly, there is not much to offer

Partially true. Professor Cohen:

"Despite the great progress in myeloma treatment, there is a group of about 10%–15% of patients whose disease returns within about a year to a year and a half after the first treatment. These are patients who are considered high-risk, and for years treatment options for them were limited and disease control was relatively short. In recent years, we have seen a change in these patients as well. Advanced immunotherapy treatments, and especially CAR-T, manage to achieve deep responses and more prolonged remissions in a large part of them than we have seen in the past. In many cases, the results are already approaching those of patients who are not defined as high-risk. Therefore, even when the disease progresses quickly, it does not mean that there are no treatment options. On the contrary — precisely for these patients, innovative treatments open up possibilities that did not exist in the past and give real hope for achieving longer control over the disease. We hope that in the near future these treatments will be available to as many patients as possible already at earlier stages of the disease."

Myth 6: Even with CAR-T, it is impossible to talk about a cure

Partially true. Professor Cohen:

"It is important to be cautious when using the word 'cure'. In medicine, it can be determined that a disease has been cured only after many years of follow-up, so it is still too early to say that CAR-T treatment cures all myeloma patients. However, the data accumulated in recent years are very encouraging. In studies with a follow-up of about five years, we see patients who received CAR-T treatment and remained without disease progression for years. In some of them, even using very sensitive methods, it is impossible to identify residual disease (MRD) — that is, no myeloma cells are found remaining in the body even after treatment. The absence of residual disease is considered a very important marker of deep remission and may also indicate a cure in the future. This is also the reason why a discussion is currently taking place at international scientific conferences on how it is correct to define a cure in myeloma and what are the criteria that will allow saying this with confidence. It is still too early to make promises, and we have a responsibility to be cautious, but for the first time we have data that allow us to be optimistic and think that this goal may be possible at least for some patients in the coming years."

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Professor Cohen, what is your main message to multiple myeloma patients?

Professor Cohen: "Multiple myeloma is still a complex disease that requires the accompaniment of expert hematologists and personalized treatment adaptation for each patient. However, in recent years there has been a dramatic change in treatment options and disease control, which can allow many patients a better quality of life and a return to daily routine. If you or a loved one are dealing with multiple myeloma, it is worth talking to the treating hematologist and finding out what treatment options might be suitable for your condition, whether there are treatment options that might be suitable, and when it is appropriate to consider advanced treatments as part of the disease treatment path."