Dostarlimab :
A New hope for treatment of colorectal cancer and endometrial cancer: Immunotherapy is one of the major strategies for cancer treatment. Immunotherapy, also known as biological therapy, uses your body's immune system to fight cancer. Cancer can survive unchecked in your body because your immune system doesn't recognize it as an intruder. Immunotherapy can help your immune system "see" the cancer and attack it.
Monoclonal antibody is an antibody produced by a single clone of cells or cell line and consisting of identical antibody molecules. A monoclonal antibody is an antibody made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibody (m Ab) is a type of protein that is made in the laboratory and can bind to certain targets in the body, such as antigens on the surface of cancer cells. There are many kinds of monoclonal antibodies, and each monoclonal antibody is made so that it binds to only one specific antigen.
Examples of monoclonal antibodies include alemtuzumab (Campath, Genzyme) for the treatment of chronic lymphocytic leukemia, and trastuzumab (Herceptin, Genentech) for the treatment of stomach and breast cancers that contain the HER-2 protein.
A cancer of the colon or rectum is located at the digestive tract's lower end.
Early cases can begin as non-cancerous polyps. These often have no symptoms but can be detected by screening. For this reason, doctors recommend screenings for those at high risk or over the age of 50. Cancer of the colon is a highly treatable and often curable disease when localized to the bowel. Surgery is the primary form of treatment and results in cure in approximately 50% of the patients. Recurrence following surgery is a major problem and is often the ultimate cause of death.
Progression of colon cancer:
Once cancer has developed in the colon, its progression will vary according to the cellular makeup of the tumor and other factors, such as the age and overall health of the patient. The general progression of colon cancer tends to be slow, but it is still a serious disease that warrants prompt medical attention.
Aged persons are at high risk for colon cancer. The risk of colorectal cancer increases as people get older. Colorectal cancer can occur in young adults and teenagers, but the majority of colorectal cancers occur in people older than 50. For colon cancer, the average age at the time of diagnosis for men is 68 and for women is 72.
Colon cancer can be diagnosed at any age, but a majority of people with colon cancer are older than 50. The rates of colon cancer in people younger than 50 have been increasing, but doctors aren't sure why.
Diet causes colon cancer in India.The studies show that people who indulge in excessive consumption of red and processed meat are at higher risk of getting the colon cancer. In other words, meals with high animal fat and cholesterol could be the major reason of the colon cancer. Diet high in fiber can be helpful to reduce the risk of colon cancer .
In USA, African-Americans have a greater risk of colon cancer than do people of other races.Excluding skin cancers, colorectal cancer is the third most common cancer diagnosed in the United States. The American Cancer Society's estimates for the number of colorectal cancer cases in the United States for 2022 are: 106,180 new cases of colon cancer. 44,850 new cases of rectal cancer.
Uterine cancer is a disease in which cancer cells form in the tissues of the uterus (womb). There are two primary types of uterine cancer: endometrial cancer, which is more common, and uterine sarcoma, which is rare. In endometrial cancer, cancer cells form in the endometrium, which is the lining of the uterus.
A new monoclonal antibody drug for Immunotherapy of colorectal cancer and endometrial cancer:
The findings concerning dostarlimab, an antibody drug, in experimental treatment of colorectal cancer patients is very encouraging but there is need for long-term studies to understand the real impact, an expert in cancer treatment has said.
"This new trial at MSKCC in a small number of patients, with locally advanced rectal cancer patients who had MMR (MisMatch repair) deficiency, have shown total disappearance of tumour without any additional treatment in all 100 percent of them. This is very encouraging but we must note that long term studies are required to understand the real impact," Dr. (Col.) R. Ranga Rao, Chairman, Oncology, of Paras Hospitals in Gurugram said.
Dostarlimab is a monoclonal antibody and is programmed death receptor-1 (PD-1) blocking monoclonal antibody.
Dostarlimab was approved for medical use in the United States (US) and the European Union (EU) in April 2021.
Medical uses of Dostarlimab:
Dostarlimab is indicated for the treatment of adults with DNA mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen.
On 17 August 2021, the
US Food and Drug Administration (FDA) granted accelerated approval to dostarlimab for adults with mismatch repair deficient (dMMR) recurrent or advanced solid tumors, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options.
Side effects of Dostarlimab:
The most common side effects reported in the US include fatigue/asthenia, nausea, diarrhea, anemia, and constipation. Additional common side effects reported in the EU include vomiting, joint pain, itching, rash, fever, and hypothyroidism (low levels of thyroid hormones).
Serious adverse reactions in >2% of patients included sepsis, acute kidney injury, urinary tract infection, abdominal pain, and pyrexia.
Immune-mediated adverse reactions can occur including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
Dostarlimab is a PD-1 inhibitor. As of 2020, it is undergoing Phase I/II and Phase III clinical trials. In 2020, the manufacturer, Tesaro, announced preliminary successful results from the Phase I/II GARNET study.
In 2020, the GARNET study announced that dostarlimab was demonstrating potential to treat a subset of women with recurrent or advanced endometrial cancer.
In April 2021, dostarlimab was approved for the treatment of recurrent or advanced endometrial cancer with deficient mismatch repair (dMMR), which are genetic abnormalities that disrupt DNA repair.
On 22 April 2021, the Food and Drug Administration granted accelerated approval to dostarlimab-gxly (Jemperli, Glaxo Smith Kline).Efficacy was evaluated based on cohort (A1) in GARNET Trial (NCT02715284), a multicenter, multicohort, open-label trial in participants with advanced solid tumors.Dostarlimab is the international nonproprietary name (INN).
Legal status of drug:
On 25 February 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization.Dostarlimab is used to treat cancer of the uterus lining (endometrial cancer,the cancer of womb in women). This medication is also used to treat certain types of tumor (solid tumors). Examples of solid tumors are sarcomas, carcinomas, and lymphomas.
Mechanism of action:
It works by changing the action of your own immune system, directing it to attack cancer/tumor cells.
Jemperli( Brand name of Dostarlimab) is a programmed death receptor-1 (PD-1)blocking antibody(Anti PD1 antibody) that works by binding to PD-1 receptor present on T cell to block interactions between PD-1 receptor and PD-L1 or PD-L2 receptor on cancer cell.This releases the PD-1 pathway-mediated inhibition of the anti-tumor immune response to kill cancer cells.
Immunotherapy with monoclonal antibodies, such as dostarlimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib and dostarlimab may kill more tumor cells in patients with cervical cancer.
Cancer cells can increase expression of PD-L1 receptor on their surface, which binds to PD-1 receptor on T cells.This reduces the immune system's(T cell's) ability to identify and attack the cancer cells.Inhibited T-Cell is activated with Jemperli.
JEMPERLI binds to PD-1 receptors on the T cells, blocking cancer cell's PD-L1 or PD-L2 receptor
interaction.This enables the T cell to identify and attack cancer cells by restoring cytotoxic activity in the T cell.
Administration of Dostarlimab :
The recommended dostarlimab-gxly dose and schedule (doses 1 through 4) is 500 mg every 3 weeks. Subsequent dosing, beginning 3 weeks after dose 4, is 1,000 mg every 6 weeks until disease progression or unacceptable toxicity. Dostarlimab-gxly should be administered as an intravenous infusion over 30 minutes.
Price of Jemperli Dostarlimab 500mg/10ml
₹ 3.40 Lakh / Vial
3.4×9= 30.6 lakh rupees for 9 doses.
Dostarlimab is a monoclonal antibody. It treats endometrial cancer and colorectal cancer.
Currently the cost is believed to be major hurdle for treatment.
Information compiled by Dr Bhairavsinh Raol
