Healthcare

Carcinoma in Situ with Cancer Immunotherapy

Dr. Vishwanath Sathyanarayanan, Consultant Medical Oncologist, Apollo Hospitals

It has been three years since The Nobel Assembly at Karolinska Institute awarded the 2018 Nobel Prize in Medicine jointly to James P. Allison and Tasuku Honjo for their discovery of novel cancer therapy by inhibition of negative immune regulation.

Their concept of stimulating the body’s immune system (taking the brakes off T cells, the main immune cells) to kill cancer cells has revolutionized cancer treatment globally including India in the past five years. With the growing cancer incidence in India of around 1.4 million people in 2020 according to the National Cancer Registry Programme (NCRP), the need for novel cancer therapy is immense to improve survival and quality of life in patients, especially with advanced cancer.

Immuno oncology is a broad term that includes several monoclonal antibodies (Mab), antibody drug conjugates (ADC), and immune checkpoint inhibitors binding to specific receptors or tumour antigens to kill cancer cells. Several Mab and ADCs have been available in the Indian market since the last decade and have led to significant improvements in survival in various malignancies.  To mention a few- rituximab, the CD 20 Mab for lymphomas, trastuzumab, a Her2 blocker for breast cancer and gastrointestinal cancers, and bevacizumab, a VEGF blocker for colonic and gynaecological malignancies are the ones which have been highly impactful. The biosimilars (biologically similar to the innovator molecules) of these drugs have significantly penetrated the Indian market and improved accessibility and affordability for cancer patients in the country.

Chimeric antigen receptor T cell therapy (CART cell therapy) is a form of immunotherapy that works on the principle of using genetically modified T cells to kill cancer cells. This treatment has been highly successful in certain high-grade relapsed lymphomas and blood cancers (acute lymphoblastic leukemias). This treatment is currently not available in India.

Therapeutic vaccines for cancer using autologous or allogeneic immune cells are in very early phase clinical trials and currently not available for commercial use.

The last past five years have seen a dramatic change in the overall treatment paradigm of various cancers with the entry of immune checkpoint inhibitors to the oncological scene. These novel drugs work on the mechanism of harnessing the immune system to kill cancer cells. Nivolumab, Pembrolizumab, and Durvalumab are the commonly used checkpoint inhibitors in India.

Programmed death-ligand -1 (PDL1) testing in the cancerous tissue using various platforms is used as a predictive biomarker for most cancers prior to considering these rather expensive drugs. Patients with metastatic solid cancers with high microsatellite instability can receive Pembrolizumab based on the FDA approval in this setting. The average cost with robust patient assistance programs of a single session of Nivolumab or Pembrolizumab is around ₹1 lakh and ₹2 lakh respectively.

These drugs are generally given once in two weeks (nivolumab) or three weeks for pembrolizumab and continued until the disease stops responding to the drug.

Only a minuscule percent of the patient population is able to afford this expensive treatment. Hence, continuing until disease progression may not be practical in the Indian scenario unless the cost comes down significantly with the availability of biosimilars.

The scene in the haematological cancer space is rather different, especially in relapsed Hodgkin lymphomas, as a salvage regimen prior to autologous stem cell transplantation (ASCT). These drugs have been quite successful in helping patients attain the desired response prior to ASCT.

Though 80-85% of patients receiving immune checkpoint inhibitors have minimal side effects, a minority do develop side effects related to autoimmunity which can manifest as pneumonia, liver enzyme elevation, endocrine abnormalities, skin rash, diarrhoea, and other organ system involvements as well.

To counter the current challenges, the establishment of a robust and accurate biomarker beyond PDL1 is the need of the hour. This will help us select a subset of patients who would possibly have the highest likelihood of responding to immunotherapy. Training subspecialists to manage immunotherapy-related side effects is also critical to improve safety concerns associated with these novel molecules. Expanding insurance coverages to include immunotherapy could be a move in the right direction to improve accessibility and affordability. The availability of biosimilars will also improve accessibility to a large extent.

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