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Multiple myeloma occurs when the bone marrow begins to produce abnormal forms of white blood cells. They build up in the body, forming tumours. Myeloma accounts for about 10% of all cases of blood cancer. The main problem in treating multiple myeloma is its frequent recurrence.
 
The treatment of multiple myeloma has improved dramatically in recent decades. Patients can live longer and better due to new drugs: proteasome inhibitors, immunomodulatory drugs, monoclonal anti-CD38 antibodies, selective inhibitors of nuclear export (SINEs), bispecific antibodies that redirect T cells, etc. In this article, we will talk about one of the newest and most promising drugs against multiple myeloma – CAR-T therapy.

 

 

What is CAR-T therapy?

car-t procedure

CAR-T therapy is a type of immunotherapy – a method of treating cancer by targeting the patient’s immune system. It involves modifying the patient’s white blood cells (T cells, hence the name of the drug) and ‘training’ them to recognise and destroy cancer cells. Multiple myeloma tends to develop rapidly and aggressively precisely because the patient’s body continues to recognise the cells affected by the disease as “its own” and does not fight it.

 

The advantage of immunotherapy compared to standard treatment regimens for multiple myeloma is that it has a targeted effect on cancer cells. This makes it different from chemotherapy or radiation therapy, which affects diseased and healthy tissues, causing different side effects – nausea, weakness, hair loss etc.

 


CAR-T therapy achieves long-term remission of myeloma disease in cases when standard treatment regimens have failed.


How can CAR-T therapy help with multiple myeloma?

After doctors modify a patient’s T cells, they begin to “track down” and destroy cancer cells in the body. The latter have a protein called BCMA, which is virtually absent in healthy tissue. The modified cells attach to it and destroy the pathogenic formations.

 

    To date, the FDA has approved two CAR-T drugs to treat myeloma disease. Abecma became available in 2021 and Carvicti became available in 2022.

 

The course of treatment results in remission – a period when doctors find no trace of cancer in the body. Unfortunately, in multiple myeloma, remission usually ends in relapse, and CAR-T therapy is no exception. There is still no possibility to completely cure the disease, and the doctor’s task in such cases is to achieve a long remission and improve the patient’s quality of life. Despite frequent relapses, the modern approach to myeloma treatment has allowed to achieve an average survival rate of +10 years, and for some people – more than 20 years. This is even though at the beginning of this millennium the average survival rate with this diagnosis was just over two years.

car-t therapy for multiple myeloma

 

    The main advantage of CAR-T therapy is that it can achieve long-term remission even when standard protocols have stopped working. This gives hope to patients who have no other treatment options left.

    Due to the selective effects of CAR-T therapy, patients have a more stable remission period. In contrast to standard treatment, there is no need to continue maintenance treatment during remission after CAR-T therapy.

 

Dr James Kochenderfer, lead researcher at the NCI Cancer Research Center, shares his experience of treating multiple myeloma patients with CAR-T therapy: “During remission, patients do not need to take any other treatment for multiple myeloma, which allows them to avoid certain side effects and ensure a high quality of life. Patients are usually very happy as they have a lot of energy for the first time in a long time.” One of Dr Kochenderfer’s first patients was able to achieve a 39-month remission thanks to CAR-T therapy after several unsuccessful attempts to treat multiple myeloma.

 

CAR-T therapy is considered one of the most promising areas in the treatment of multiple myeloma, and by far the greatest amount of research is being conducted in this area. Potentially, future drugs will make it possible to achieve longer and more stable remission. One interesting option, which is already in the trial phase at the renowned Sloan-Kettering Cancer Centre, is allogeneic CAR-T therapy. This is the same type of immunotherapy, but it is not made individually from each patient’s cells but from healthy donor T cells. When a patient with myeloma disease needs treatment, doctors will simply pick up ready-made modified CAR-T cells from the closest donor. This method of treatment requires only a few days rather than weeks, saving valuable time.

 

How effective is CAR-T therapy?

Chemotherapy for synovial sarcoma

The first large study that gave Abecma FDA approval showed a positive effect in 72% of patients. Among them, 28% managed to completely get rid of all tumours. Subsequent trials conducted at individual medical centres have achieved success rates of up to 90%.

 

The length of expected remission after CAR-T therapy depends on various factors, such as the patient’s age and stage of disease, as well as the results of certain tests. On average, various studies, including those published in the prestigious medical journal Lancet, show remission durations ranging from 8 to 19 months. However, for some patients, the remission period can be longer, up to 2-3 years.

 

Unfortunately, due to the nature of the disease, most patients relapse.

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Indications and contraindications for treatment

    CAR-T therapy is used only for the treatment of relapsed multiple myeloma after a minimum of 4 previous cycles of treatment using standard protocols have been completed.

 

Official international guidelines include the following criteria for patients:

 

    иконка галочкиConfirmed diagnosis of multiple myeloma. 

    иконка галочкиA minimum of four previous unsuccessful courses of treatment, or 

    иконка галочкиThe disease has relapsed after a minimum of four previous courses of treatment. 

    иконка галочкиPrevious therapy must have included proteasome inhibitors, immunomodulatory drugs, and anti-CD 38 monoclonal antibodies. 

    иконка галочкиThe disease must be stable enough for patients to remain in good enough condition to receive infusions after the end of the production period. The European Society for Blood and Marrow Transplantation recommends a predicted survival of more than 6-8 weeks. 

    иконка галочкиAdequate cardiac, respiratory and renal function. 

 

Acute infections, recent surgery and vaccination within the last 4 weeks are temporary contraindications to CAR-T therapy.

What should a patient expect from the procedure?

 

Before treatment, each patient must undergo a thorough diagnostic evaluation to ensure that the treatment will be effective and safe. The examination package usually includes an extended blood test with biochemistry and an assessment of heart and lung function. The patient must be in a stable condition before starting treatment.

    T cells are taken from the patient’s blood through a process called apheresis. The patient is hooked up to a machine that filters the blood, selecting the white blood cells needed and sending the rest back into the bloodstream.


    The collected blood cells are sent to a laboratory where they are genetically modified to “train” them to recognise myeloma tumours.


    During this period, the patient’s immunity is weakened, and myeloma disease can enter a phase of rapid progression. For this reason, patients necessarily remain in hospital under so-called “bridge” treatment to prevent such a development.


    CAR-T cells take 3-4 weeks on average to modify, mature and multiply.


    When the drug is ready, it is administered to the patient. Once in the body, CAR-T cells continue to multiply, while recognising and attacking myeloma cells.

 

After this stage, patients need to stay in the cancer centre for approximately two more weeks as an inpatient. CAR-T therapy can cause dangerous side effects. To avoid and control them, 24-hour medical supervision is necessary.

 

The most dangerous of the possible complications of CAR-T therapy is cytokine release syndrome, which can be fatal. However, this scenario is very rare. The treatment can also lead to:

 

    иконка галочки“Macrophage activation syndrome” (accompanied by fever and high blood pressure); 

    иконка галочкиThrombocytopenia (vulnerability to severe bleeding); 

    иконка галочкиBrain disorders (confusion, seizures, tremors, loss of speech and delirium); 

    иконка галочкиNeutropenia (vulnerability to infections). 

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Patient story

Diamantis Sinis was one of the first people to have the opportunity to be treated with CAR-T therapy for multiple myeloma, even before the drug became widely available. As of 2018, he has managed to undergo several courses of standard treatment with a variety of treatments, including several chemotherapy and targeted therapy protocols. The man even underwent an autologous bone marrow transplant, but even this did not help – the disease relapsed again and again.

 

Finally, in 2020, at the age of 59, he asked his doctor to find a solution and the doctor suggested that he take part in a clinical trial of CAR-T therapy. And it turned out to be the right choice. After the previous 2 years of heavy and exhausting treatment, Diamantis managed to achieve a two-year remission. Without the constant exhaustion of chemotherapy, he was finally able to regain his strength, enjoy life again and devote his time to his family.


“This disease mowed me down and for a long time nothing helped me at all. Thank God that there are doctors among us who are developing medicines against myeloma. Thanks to them, I have a second chance.”


multiple myeloma patient's story

Clinics and treatment prices

CAR-T therapy is individually created for each patient with multiple myeloma. This treatment requires a high-quality, state-of-the-art laboratory and special certification for cell engineering.

 

In addition, multiple myeloma treatment involves a multidisciplinary team of specialists, each of whom must have sufficient experience with the disease to effectively manage it and prevent severe complications of treatment. The composition of this team may vary but should include haematologists, neurologists, cardiologists, intensive care unit specialists, infectious disease specialists, pharmacists, nurses, blood transfusion specialists and a CAR-T coordinator.

The approximate price of CAR-T therapy for multiple myeloma abroad is as follows:

 

CountryCost
флаг турцииTurkey$120,000-$150,000
флаг кореиSouth Korea$180,000-$240,000
флаг израиляIsrael$80,000-$150,000
флаг испанииSpain€380,000-€440,000
флаг китаяChina$60,000-$120,000

 

Among the foreign clinics offering this treatment method, we primarily recommend those with the best value for money:

 

 

 

 

    Summary

    иконка галочкиCAR-T therapy is one of the treatment options for multiple myeloma, used for the recurrent form of the disease after a minimum of 4 failed courses of the standard treatment protocol. 

    иконка галочкиCAR-T therapy involves modifying the patient’s immune cells to recognise and destroy tumours. The drug is made individually for each patient. This process takes an average of 3-4 weeks. 

    иконка галочкиAbout 70-90% of patients with myeloma disease respond positively to CAR-T therapy, achieving long-term remission. About a third of these patients succeed in completely eradicating all tumours. 

    иконка галочкиCAR-T treatment does not require maintenance therapy for the remission period. It does not come with the same debilitating side effects as some chemotherapy protocols; however, it does have its own set of possible complications. 

    иконка галочкиThe cost of multiple myeloma CAR-T therapy treatment abroad starts at $60,000. Among the clinics we recommend are Acibadem (Turkey), Souraski (Israel), Quironsalud (Spain), SoonChunHyang (South Korea), and Fuda (China). 

 

Stay with MediGlobus and keep up to date with the latest news about medical advances abroad. If you need oncology care abroad, please submit a request. Our coordinators will help you find a clinic that will offer you a treatment programme that will help you.

CAR-T therapy for multiple myeloma

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Sources:

  1. 1. FDA Approves BCMA-Targeted CAR T-Cell Therapy for Multiple Myeloma
  2. 2. American Cancer Society
  3. 3. Frontiers in Immunology
  4. 4. Blood and Lymphatic Cancer: Targets and Therapy
  5. 5. Off-the-Shelf CAR T Cell Therapy for Multiple Myeloma Shows Promise
  6. 6. The CAR T-cell therapy from the Hospital Clínic-IDIBAPS for multiple myeloma is effective in patients with refractory disease
  7. 7. MyelomaUK
  8. 8. CAR T-cell Therapy: Multiple Myeloma
  9. 9. CA: A Cancer Journal of Clinicians
  10. 10. Hematology, Transfusion and Cell Therapy
  11. 11. Lymphoid Neoplasia
  12. 12. The Lancet
  13. 13. Cancer Epidemiology


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