Killing me softly…

Colloquially, lymphoma is a type of cancer affecting the immune system. Today, thousands suffer from lymphoma in India, and millions across the globe. Sachin Jagdale reviews the research and viewpoints of oncologists on this 'silent killer'

Conventional wisdom holds that human beings are responsible for their own health and can prevent disease. However, cancer is a 'silent killer', for which there is no fool-proof prevention therapy. This has baffled the international research community. Cancer is of different types, having different kinds of symptoms, characteristics, origins etc. It varies even in the way of expression. One of the deadliest types of cancer is Lymphoma, perhaps the fastest growing forms of cancer in the world today.

Lymphoma is the broadest category of a family of related blood cancers, involving a group of cells, called the lymphocytes, which in turn make up the lymphatic system—a part of the immune system. There are about 40 different kinds, subtypes or variations of lymphoma. Lymphoma has been classified in to two prime categories—Hodgkin's lymphoma and non-Hodgkin's lymphoma—named after Thomas Hodgkin, who first described Hodgkin's lymphoma in 1832. Hodgkin's lymphoma was one of the first cancers to be cured by radiation and later by combination therapy. Reed-Sternberg cell (a B lymphocyte) is an abnormal cell type present in Hodgkin's lymphoma, but absent in the second type of lymphomas, therefore referred to as non-Hodgkin's lymphomas (NHL).

Research is crucial

"Molecular research is expected to refine classification which may help in deciding treatment. This will also help in giving individualised treatment" - Dr Kumar Prabhash Oncologist Tata Memorial Hospital

Scientists are exploring the genetic roots of lymphoma. The research on changes in DNA, which in turn results in transformation of a lymphatic cell into a lymphoma cell, has been providing insight to rapid growth of these cells. The success of this study will ensure the development of the drug that will block this process. The findings of such research have already led to extremely sensitive tests like polymerase chain reaction (PCR) that can detect one lymphoma cell among million normal cells. Oncologists have been using this technique to determine the efficacy of the treatment. Dr Kumar Prabhash, an oncologist at Tata Memorial Hospital, Mumbai, shedding more light on the current research developments on lymphoma, says, "Research is happening on various aspects of lymphoma. There is no known cause for most lymphomas at present. There has been intense research on genetic and molecular changes in lymphoma, which may finally give insight into causes of most of the lymphoma."

"Lymphoma research is focused on different modalities and novel molecules. These include immunosuppressant drugs, T-cell immunotherapy, HDAC inhibitors, antisense oligonucleotide molecules and proteasome inhibitors" - Ajay Vij Chief Executive Officer Dabur Pharma

There are several different methods used to classify NHL. World Health Organization (WHO) has come up with a new way of classification wherein the appearance of lymphoma cells, chromosome features of the cells and the presence of certain chemicals on the cell surface are taken into consideration. Prabhash cites, "Molecular research is expected to refine classification which may help in deciding treatment. This will also help in giving individualised treatment. We usually classify lymphoma in various risk groups which helps in prognostication and also in deciding treatment." DNA microarray is a recent breakthrough that has revolutionised the science and medical field. It is a great step towards more accurate diagnosis of lymphoma and tailoring treatments for each patient. Research is a precursor for the launch of any new treatment.

"In many tertiary cancer centres in India, the treatment does match international standards. Most patients that are diagnosed with advanced cancer don’t have the financial resources to avail standard therapy" - Dr Nilesh Lokeshwar Oncologist Raheja Hospital

Dr Nilesh Lokeshwar, an oncologist at the Mumbai-based Raheja Hospitals, says, "Ongoing research in cancer is extremely essential so as to provide more effective and safer drugs against cancer. Research in the field of oncology has led to better understanding of the mechanisms and biology of cancer. Specifically, knowledge of the disturbed molecular pathways in cancer has led to the identification of newer drug targets. This has significantly improved our drug arsenal against cancer (targeted agents, monoclonal antibody)." He adds, "Development of drug resistance is an important cause of treatment failure and current studies are focusing on ways to overcome drug resistance." According to Ajay Vij, CEO, Dabur Pharma, lymphoma research is focused on different modalities and novel molecules. These include immunosuppressant drugs, T-cell immunotherapy, HDAC inhibitors, antisense oligonucleotide molecules and proteasome inhibitors.

Hitting bull's eye

The right combination of treatments and on-time treatments are the two most crucial factors while treating lymphoma, or any other cancer. Usually the patient or doctor learns about the cancer when it is already in an advance stage. Over the years, cancer treatments and therapies have witnessed a remarkable change. Side-effects after the high doses of medicines have remained a big concern for doctors, as well as patients for a long time. However, today, scientists have been successful in minimising these side-effects to some extent by applying targeted therapies.

"Rituximab (Mabthera-Roche) is an anti-CD 20 monoclonal antibody that targets lymphoma cells that express CD 20 on their surface. In combination with CHOP chemotherapy, Rituximab has been shown to significantly improve response rates and survival in patients with CD 20 positive lymphomas. Other examples of targeted therapies in the treatment of lymphomas include the radio immunoconjugates, which is a combination of anti-CD 20 monoclonal antibody and a radioactive source (Bexxar-GlaxoSmithKline and Zevalin-Biogen)," says Lokeshwar. However he cautions, "This form of therapy is not yet available in India."

The third crucial aspect of cancer therapy is hitting the right price. There has always been a traditional symbiotic relationship between doctors and pharma companies, which becomes more crucial in the oncological therapeutic segment. Given that oncological therapies are long term and more expensive than medications in other segments, it becomes the combined responsibility of doctors and pharma companies to consider the patient's welfare, by making cancer therapy more accessible. "Oncologists and pharma companies are both part of the healthcare industry. Besides being a professional in this industry, all stake holders have to understand that this is direct human angle of suffering. It is the duty of oncologists and pharma companies to work together for helping patients. Pharma companies should make better drugs at reasonable costs. Oncologists and pharma companies should collaborate in the development of newer and better molecules," opines Prabhash.

Pros and cons

Cancer patients often opt to go abroad for treatment. However, this avenue is not an option for every cancer patient considering the costs involved in such treatments. The question is why do cancer patients seek treatment abroad? Are Indian hospitals not equipped enough to provide world class treatment? Or do Indian doctors lack the skills available overseas? Lokeshwar analyses the issue. He says, "In many of the tertiary cancer centres in India, treatment of cancer does match international standards. However, this is not true for our patients in other parts of the country. Most of our patients are diagnosed with advanced cancer and do not have the financial resources to avail standard therapy. The addition of Rituximab to CHOP chemotherapy in the treatment of lymphoma increases the cost from Rs 5,000 per cycle to Rs 1,00,000 per cycle."

Oncology has evolved in a great way. New techniques of diagnosis, treatment and screening have made a great contribution in decreasing the mortality rates due to the lymphoma and various other types of cancer. It will be interesting to see in future what kind of treatments we are going to witness. According to Prabhash, there has been an explosion of research in targeted therapy and it appears that in the future, the major interest is going to be in this area. Oncologists definitely want a hundred percent cure for lymphoma, but there is a huge gap between expectation and reality.

sachin.jagdale@expressindia.com