Advancements in blood cancer treatments expand patient options
A haematologist provides insights into lymphoma, its risk factors and therapeutic pathways.
Emerging therapies provide new avenues for blood cancer patients. Photos: Gilead Sciences Europe
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Every 25 seconds, someone in the world is diagnosed with a blood cancer1. These cancers, including widely recognised forms such as lymphoma, myeloma and leukaemia, are increasing globally with 1.25 million new cases reported each year.
Lymphoma, a cancer where infection-fighting white blood cells (lymphocytes) undergo malignant changes and form tumours, is particularly prevalent. In Singapore, it ranks as the fourth most common cancer in men and the fifth in women.
Dr Daryl Tan, a haematologist from the Clinic For Lymphoma, Myeloma And Blood Disorders at Mount Elizabeth Novena Hospital, explained that while there is no single cause for lymphoma, several risk factors like age, gender and infection exposure can contribute to its development.
“Most lymphoma cases are diagnosed in patients above 60,” he noted. “This is due to the increased likelihood of genetic mutations accumulating with age, potentially leading to aggressive blood cancers.”
Additionally, individuals with weakened immune systems – be it due to autoimmune diseases, immunosuppressive drugs for organ transplants or exposure to viruses such as Epstein-Barr, hepatitis B or C – face a higher risk of developing lymphoma.
RISK FACTORS AND KEY SYMPTOMS
Men are more likely to develop certain types of lymphoma compared to women. In particular, diffuse large B-cell lymphoma (DLBCL), an aggressive form of the disease, is more common in men.
According to Dr Tan, the reasons for this difference are not fully understood. “Potential contributing factors include hormonal differences, genetic predisposition, varying environmental exposures between genders and subtle variations in immune system function. More research is needed to determine the precise reasons behind this disparity.”
DLBCL affects the lymph nodes, with symptoms including unexplained fevers, fatigue, coughs and swollen lymph nodes in the neck, groin or armpits. The wide range and severity of these symptoms can potentially delay diagnosis, as patients may ignore the signs or attribute them to other causes like the flu.
“DLBCL can also present with less obvious B-symptoms, also known as general indicators of a more aggressive disease,” shared Dr Tan. “These encompass unexplained weight loss, night sweats and itching, which are often mistaken for an infection.”
He urges anyone experiencing these symptoms to consult a doctor for further investigation.
TREATING DLBCL
“The goals of DLBCL treatment are to minimise symptoms, achieve or prolong remission and improve patients’ quality of life. Whenever possible, we also aim for curative therapy, which seeks to completely eradicate the disease,” said Dr Tan.
For those diagnosed with DLBCL, various treatment options are available. The primary approach, known as frontline treatment, includes chemoimmunotherapy. This method combines chemotherapy drugs to kill or slow the growth of cancer cells with immunotherapy, which boosts the immune system’s ability to fight cancer.
Some DLBCL patients, however, face the disheartening reality of relapse or treatment resistance after frontline treatment, said Dr Tan. For these patients, second-line treatment is available. This often involves high-dose chemotherapy, followed by a bone marrow transplant. The procedure infuses the patient’s bone marrow with either their own or donated filtered stem cells to stimulate the production of healthy blood cells.
Bone marrow transplants typically require patients to respond to high-dose chemotherapy, which some may not be able to tolerate due to considerations such as organ function, overall fitness level and disease status.
Unfortunately, studies have shown that up to 50 per cent of these patients will continue to relapse after second-line treatment.
Dr Tan explained that this highlights the complex nature of DLBCL, where multiple factors such as intrinsic resistance (the ability of cancer cells to resist treatment), new cancer cell mutations or changes to the tumour cell environment may contribute to treatment failure.
ADVANCES IN TREATMENT OPTIONS
“Recent developments in chimeric antigen receptor T-cell (CAR-T) therapy have enhanced blood cancer treatment options, particularly in the management of primary refractory (treatment-resistant) and early-relapse DLBCL after frontline treatment,” Dr Tan noted.
CAR T-cell therapy is a form of immunotherapy that modifies a patient’s immune cells to fight cancer.
“It does not rely on external donors,” he explained. “Instead, the therapy uses the patient’s T-cells, a type of white blood cell that plays a key role in the immune response.”
T-cells harvested from the patient’s blood are sent to a specialised laboratory where they are genetically engineered to express chimeric antigen receptors designed to recognise specific proteins found in lymphoma cells. Once reintroduced into the patient’s bloodstream, these modified T-cells can identify and attack lymphoma cells.
“Studies2 have shown that this treatment offers clinical benefits, including a shorter treatment duration and lasting effects, as the modified T-cells can remain in the body,” said Dr Tan.
He added that other findings3 indicate that patients with relapsed or refractory large B-cell lymphoma (LBLC) who responded favourably to CAR T-cell therapy in the second-line setting generally required less subsequent therapy compared to those who received it as third-line treatment.4
“Participants in some studies reported improvements in their well-being six months after receiving CAR T-cell therapy, including reduced physical symptoms and lower anxiety levels,” said Dr Tan. “However, each DLBCL patient’s case is unique and not all patients are suitable for CAR T-cell therapy. Patients should discuss with their doctor to evaluate if they are suitable candidates for CAR T-cell therapy*.”
HOPE FOR A BETTER TOMORROW
According to Dr Tan, beyond the physical challenges of lymphoma and its treatment, patients often experience emotions such as anxiety, sadness and anger, as well as worry about relapse. A strong support network of family, friends and healthcare providers can help patients stay resilient.
“Advocate for yourself by asking questions and actively participating in your care and treatment plan. Prioritise rest, nutritious food and gentle movement whenever possible,” he advised.
There is a broadened availability of CAR T-cell therapies in Singapore for the treatment of several types of blood cancer, including DLBCL and B-cell acute lymphoblastic leukaemia. In DLBCL, CAR T-cell therapy was previously available only to patients who had undergone two or more unsuccessful prior treatments and were on their third-line therapy or beyond.
Dr Tan believes that more approvals for CAR T-cell therapies will follow as progress in the field continues.
“It’s important for patients to hold onto hope, fuelled by the ongoing advancements in treatment worldwide,” he said. “You are stronger than you think. With courage and resilience, you can navigate this challenge.”
If you’ve been diagnosed with a blood cancer, speak to your doctor to learn more about suitable treatment options.
*CAR-T may not be an appropriate treatment for all individuals and is typically reserved for patients with specific blood cancers who have not experienced success with other therapies. As with any medical procedure, CAR T-cell therapy carries potential risks and side effects. A thorough discussion with a qualified healthcare professional is crucial to determine if the treatment is suitable for your circumstances.
1Shapira, Shiran et al. Feasibly of CD24/CD11b as a Screening Test for Haematological Malignancies. Journal of personalized medicine vol. 11,8 724. 27 Jul. 2021, doi:10.3390/jpm11080724
2Rutgers Cancer Institute, Advantages of CAR T-cell therapy. Available via: Advantages of CAR-T Cell Therapy | Rutgers Cancer Institute of New Jersey (cinj.org) Accessed July 2024
3Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133
4Westin, J, and Sehn, L. H. CAR T cells as a second-line therapy for large B-cell lymphoma: a paradigm shift? Blood 2022; 139 (18): 2737–2746. doi: https://doi.org/10.1182/blood.2022015789
