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Is CAR T-cell therapy a boon for multiple myeloma patients??

Multiple myeloma (MM) or Kahler’s disease is a disorder seen in the spine, skull, pelvis and ribs. The disease usually occurs in the bone marrow due to the overproduction of abnormal proteins from plasma cells, a type of white blood cell that plays a crucial role in the immune system. Symptoms include anemia, hypercalcemia, renal dysfunction, bone pain, and sometimes amyloidosis( a rare disease that occurs due to the excessive deposition of protein in the body) [1].


What is the need for advanced treatment in mm?


The conventional treatment for multiple myeloma consists of:

  • Chemotherapy: Cyclophosphamide, doxorubicin, and etoposide are the commonly used chemotherapeutic agents in multiple myeloma. They can be given along with corticosteroids to control the inflammation in the disease.

  • Autologous stem cell transplant: Induction therapy with chemotherapeutic agents is given before stem cell transplantation, to necrotize the tumor cells. Stem cells from either the bone marrow or blood of the same patient or other family members are transferred to the damaged site to stimulate the formation of new bone in MM patients.

  • Radiotherapy: It can be given along with or before or after chemotherapy as an adjuvant therapy to necrotize the tumor cells.

  • Surgery: Surgery is the oldest method used to remove a single mass of tumor in multiple myeloma. When compression of the spinal cord occurs due to the overgrowth of the tumor mass, surgical removal of the tumor is the immediate mode of treatment.

According to the literature all these modes of conventional treatment resulted in recurrent cases of multiple myeloma. So to minimize the recurrent/refractory cases advancements in drugs like immunomodulatory drugs, stem cell therapy, targeted therapy, gene therapy, and monoclonal antibodies, and CAR T-cell therapy were considered. Additionally, they have fewer side effects compared to conventional methods [2].


What is car t-cell therapy?


  • CAR T-cell therapy is a type of targeted therapy.

  • It is a technique where T–cells (type of white blood cells) are modified in a way that will cause them to combat cancer by destroying cancer cells.

  • Because CAR T-cell therapy involves changing the genes inside T-cells to enable them to fight cancer, it is often referred to as cell-based gene therapy.

  • This CAR T-cell therapy is useful in the treatment of many cancers including multiple myeloma.

  • It is particularly beneficial in refractory/recurrent cases and drug-resistant cases of multiple myeloma.

  • T-cells used in CAR T-cell therapy are extracted from the blood of the patient and altered in a laboratory by adding a gene for a receptor (known as a chimeric antigen receptor or CAR), which modifies the T cells to adhere to a particular cancer cell antigen. These modified T-cells are then injected back to the patient [3].


How CAR T-cell therapy affect mm?


FDA approved two CAR T-cell therapies for multiple myeloma till now:

  • Idecabtagene vicleucel available under the trade name Abecma® was approved on March 26, 2021. This is the first cell-based gene therapy for multiple myeloma that the FDA has approved.

  • Ciltacabtagene autoleucel available under the trade name Carvykti® was approved on February 28, 2022. This is the second treatment approved by FDA for MM.

The mechanism of action of these drugs is it contains the T-cells that are extracted from MM patients, which are altered in such a way that they act on B-cell maturation antigen-BCMA gene(a gene that is essential in the pathogenesis of MM) T his will make these drugs to fight with MM. These two CAR T-cell therapies are used for the treatment of adult patients who are reported with recurrent cases of multiple myeloma even after administering four or more prior lines of therapy. This therapy contains three major classes of myeloma drugs including immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies.


Multiple myeloma

However, this therapy also has some disadvantages which can result in long-lasting remissions in advanced cases of cancer. Also, neurological side effects including speech difficulties, tremors, psychosis, and seizures are reported in some cases. One major side effect of this therapy is cytokine release syndrome (an acute systemic inflammatory syndrome characterized by fever and multiorgan dysfunction) which makes this therapy contraindicated in older people due to their low immunity status [4].


CAR T-cell therapy ought to be tried!


Despite of its disadvantages, CAR T-cell therapy is an effective regime in recurrent/refractory cases of MM where other treatments have failed. The new drugs in this therapy are approved by FDA based on the results of the clinical trials conducted. So further studies are required for the emergence of newer drugs in this therapy, which have fewer side effects and more clinical benefits for MM patients.


References


1. “FDA Approves Carvykti CAR T-Cell Therapy for Multiple Myeloma - NCI,” Mar. 30, 2022. https://www.cancer.gov/news-events/cancer-currents-blog/2022/fda-carvykti-multiple-myeloma (accessed Feb. 14, 2023).

2. C. for D. E. and Research, “FDA approves idecabtagene vicleucel for multiple myeloma,” FDA, Jun. 2021, Accessed: Feb. 14, 2023.Available: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-idecabtagene-vicleucel-multiple-myeloma

3. “CAR T-Cell Therapy for Multiple Myeloma: Effectiveness vs. Risks.” https://www.webmd.com/cancer/multiple-myeloma/car-t-cell-therapy-multiple-myeloma (accessed Feb. 14, 2023).

4. “CAR T-Cell Therapy for Patients with Multiple Myeloma: Current Evidence and Challenges - PMC.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9439649/ (accessed Feb. 14, 2023).

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Collaborators

IIT Guwahati
University of Manchester
Rhenix Lifesciences
American university of Sharjah
IIT Delhi
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