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Is Teclistamab effective for multiple myeloma??


Multiple myeloma

Multiple myeloma (MM), a hematological disorder is commonly seen in elderly people. Even though it is a rare occurrence, it is the second most common malignancy among blood disorders. It mainly arises due to the defective plasma cells (B lymphocytes get altered due to cancer antigen) due to which abnormal proteins (M-protein) are secreted into the blood. These proteins cause manifestations that range from anemia to amyloidosis. Other symptoms include kidney failure, hypercalcaemia and bone pain [1].


What is the scope of treatment in mm?

  • The traditional treatment for multiple myeloma includes chemotherapy, radiotherapy (either given after chemotherapy or in combination with it), stem cell transplant and surgery (for a single mass of tumor).Due to the unavoidable side effects and more cases of recurrence in conventional treatment, newer treatment options were developed for MM patients.

  • This includes immunomodulatory drugs, monoclonal antibodies, proteasome inhibitors, stem cell therapies, nanotechnology drugs, nutraceuticals (substances that have physiological benefits), and CAR T-cell therapies (T–cells are modified to fight against cancer).

  • All these drugs are shown to be more effective in MM patients compared to the traditional modes of treatment. But they are also associated with common side effects like nausea, vomiting, hair loss, low blood cell counts, and serious side effects like nerve damage and kidney failure [2].


What is Teclistimab?

  • Teclistamab available under the trade name Tecvayli® belongs to the group of monoclonal antibodies.

  • It can bind two different targets at the same time which is why it is also called bispecific antibody.

  • The underlying mechanism of action of this drug is that it modifies the T-cells to bind B cell maturation antigen (BCMA), a protein that is present on the plasma cells and is more evident in multiple myeloma patients.Additionally, it also has the capacity to bind to the CD3 (cluster of differentiation) protein present on T-cells.

  • Ø By bringing them together, this drug serves as a bridge between the myeloma and T-cells. It helps the T-cells to recognize the myeloma cells and destroy them [2].


How does Teclistamab work in mm?

  • Efficacy of Teclistamab in multiple myeloma is evaluated by the results obtained from the clinical trials.

  • In the trial, teclistamab (Tecvayli) was administered to patients with multiple myeloma that had not responded to at least three different cancer treatments that are routinely used or patients who had a relapse of MM.

  • Over two-thirds of trial participants experienced at least a partial response to teclistamab, and nearly 40% had complete relief from the malignancy. The study also discovered that patients receiving teclistamab had a median survival period of roughly eleven months without their malignancy getting aggravated [3].

  • Based on these trial results, teclistamab was approved by FDA on October 25, 2022, for treating recurrent cases of multiple myeloma.

  • FDA also approved CAR T-cell therapies for recurrent cases of MM. The main difference between these therapies is that CAR T-cell therapy acts only on BCMA protein present on myeloma cells whereas teclistamab act on both BCMA and CD3, thus justifying its role as a bispecific antibody.

  • Another difference is, in CAR T-cell therapy patients T-cells should be taken out, modified, and re-injected back which is not required with teclistamab.

  • Although Teclistamab has lower efficacy in reducing MM compared to CAR T-cell therapy, it is usually preferred for old patients (with low immune status) who had recurrent MM, due to the lower incidence of cytokine release syndrome (syndrome associated with high fever and multiorgan dysfunction).

  • The only disadvantage of Teclistamab is that it has to be infused weekly (to monitor cancer) unlike CAR T- cell therapy which works well with a single infusion [4].


Necessity is the mother of invention!


CAR T-cell therapy is a boon to patients who suffer from recurrent MM or in whom conventional treatment failed. But its side effects (cytokine release syndrome) limit its usage in older patients which led to the discovery of Teclistamab. Similarly continuous research and clinical trials are required for the development of newer drugs that shows better efficacy and mild side effects in recurrent case of MM.


References


1. “Tecvayli Produces Promising Results in Multiple Myeloma - NCI,” Sep. 29, 2022. https://www.cancer.gov/news-events/cancer-currents-blog/2022/tecvayli-multiple-myeloma (accessed Feb. 15, 2023).

2. FDA Approves Teclistamab, a Promising New Drug for Multiple Myeloma Targeting BCMA and CD3 Proteins | Memorial Sloan Kettering Cancer Center,” Oct. 25, 2022. https://www.mskcc.org/news/fda-approves-teclistamab-promising-new-drug-multiple-myeloma-targeting-bcma-cd3-proteins (accessed Feb. 14, 2023).

3. Janssen Research & Development, LLC, A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Teclistamab, a Humanized BCMA x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma,” clinicaltrials.gov, Clinical trial registration NCT04557098, Jan. 2023. Accessed: Feb. 13, 2023. [https://clinicaltrials.gov/ct2/show/NCT04557098]. Available: https://clinicaltrials.gov/ct2/show/NCT04557098

4. C. for D. E. and Research, “FDA approves teclistamab-cqyv for relapsed or refractory multiple myeloma,” FDA, Oct. 2022, Accessed: Feb. 15, 2023. [https://www.onclive.com/view/fda-approves-teclistamab-cqyv-for-relapsed-or-refractory-multiple-myeloma]. Available: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma.

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Collaborators

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