Current challenges and emerging treatments for thalassaemia: A hematologist perspective
INTRODUCTION
Dr. Ahmed Farrag is a hematology and internal medicine specialist at the Thalassemia Centre at Latifa Women and Children Hospital in Dubai, UAE. He focuses on hemoglobinopathies and chronic patient care and has been working at the Centre since 2013. He completed a Bachelor of Medicine degree in 2002 and a Master of Internal Medicine and Hematology degree in 2009 from Alexandria University in Egypt. He began his career as a hematology resident at Alexandria University Hospital for five years and led the Middle East hemato-oncology center as a General Director for two years. He served as an investigator in several clinical trials, including PANORAMA, EXTnd, and ECLIPSE. He has published two clinical papers and five international conference abstracts. In this current role, Dr. Ahmed discusses the challenges faced by thalassaemia patients and shares his take on the new emerging therapies.
Thalassaemia is a genetic disorder that affects the production of normal hemoglobin required for oxygen transport in the blood. People with thalassaemia are anaemic (1). Different types of thalassaemia include alpha and beta thalassaemia, classified based on the type of gene affected. The current treatment guideline includes blood transfusion for anaemia, the frequency of which depends on the severity of the disease. Iron overload in the blood is a common complication resulting from blood transfusions and could affect the normal functioning of the heart, liver, and hormones. Chelation therapy is then required to remove excess iron from the blood. Dr. Ahmed shares the current treatment options, the challenges faced by the patients, and how emerging treatments can rectify some of the problems.
DIFFICULT TIMES FOR THALASSAEMIA PATIENTS
Dr. Ahmed explains, “The main challenges for thalassaemia patients include equity of care; the cost of medications; long-term care; iron overload complication (for blood transfusion-dependent patients); blood shortage, especially during a crisis or lockdowns; and lack of community awareness of the disease.”
Elaborating on each topic – according to a study published in 2022 (2), the estimated cost to treat a transfusion-dependent thalassaemia child up to the age of 16 in Dubai, UAE, comes close to AED 1.2 million. Therefore, the cost of thalassaemia treatment places a heavy burden on the patients and the healthcare system. Adding to this is the variability based on the patient’s age, gender, and the extent of complications associated with the disease.
Moving to the other factors Dr. Ahmed listed – thalassaemia patients who depend on blood transfusions, require lifelong treatment and iron chelation therapy. Therefore, long-term management of the disease is paramount. Additionally, blood transfusions often lead to iron overload, impairing the immune system and increasing the risk of infection, illness, and organ damage, such as cirrhosis, diabetes, heart disease, and hypogonadism (2).
Dr. Ahmed points out that, especially during the COVID pandemic and the lockdown, there was a blood reserve shortage, significantly impacting transfusion-dependent thalassaemia patients. Measurements must be in place to secure sufficient blood supply to better prepare for future crises. Lastly, Dr. Ahmed highlights the importance of education campaigns and the initiatives needed to raise community awareness of the disease.
BETTER OPTIONS ARE IN PLACE
Reblozyl® (3) is an erythroid maturation agent (EMA) which helps in the maturation of healthy red blood cells (RBCs). Reblozyl® is indicated for adults with beta-thalassaemia who need regular blood transfusions. It is gaining popularity among hematologists due to its potential capability to reduce the frequency of RBC transfusions. Dr. Ahmed shares his experience with his patients administering Reblozyl; he explains, “Of course, it has a positive impact. It is working efficiently to keep patient hemoglobin levels on the higher side and to decrease the transfusion units per visit.”
But Reblozyl is an expensive medication; therefore, accessibility is a concern. Dr. Ahmed says, “The cost-effective ratio is not well studied, and it needs to be estimated given the high cost of the medicine.” Dr. Ahmed also points out that although Reblozyl has had a positive outcome, the long-term effects need further evaluation.
GRADUALLY SAYING GOODBYE TO IRON CHELATION THERAPIES
Iron chelators such as Deferasirox, Deferiprone, and Deferoxamine are used to remove excess iron from the body (2). But iron chelation therapy contributes to approximately 60% of the direct medical costs (2). Newer treatments aim to promote erythropoiesis and, if administered early, could lead to reduced usage of iron chelators. Dr. Ahmed says, “It is clearly noticed that serum ferritin dropped dramatically over time with new therapies. Many patients who are taking the new promoting therapy of erythropoiesis have decreased their chelation therapy dose.” For some patients, it has worked so wonderfully that they have low levels of serum ferritin even in the absence of the medication. This is a radical shift in the beta-thalassaemia field.
GENE THERAPY: THE ACTUAL CURE
Gene therapy is gaining much attention in treating several genetic disorders. The Food and Drug Administration (FDA) recently approved a cell-based gene therapy named Zynteglo® to treat beta-thalassaemia (4). But will gene therapy be available in the UAE? Dr. Ahmed comments, “It is still unavailable in the UAE or even the Middle East. I think it will be accessible soon.”
Overall, gene therapy for beta-thalassaemia is still a far-fetched reality for the majority of patients, the main barrier being the cost. Most patients in need of gene therapy take the overseas treatment route. But this is far from the best option. Dr. Ahmed says, “If patients travel abroad for treatment, there is also the cost of travel and accommodation.”
There is hope for thalassaemia patients as new therapies emerge and offer a better quality of life. Correcting the faulty gene through cell/gene therapy can alter the disease state, however, the accessibility of the treatment is still a big question and warrants immediate attention.
Sources
- Thalassaemia. Accessed 27 January 2023. https://www.nhs.uk/conditions/thalassaemia/
- Alshamsi S, Hamidi S, Narci HC. Healthcare resources utilization and direct costs of transfusion-dependent thalassaemia patients in Dubai, United Arab Emirates: a retrospective cost-of-illness study. BMC Health Services Research. 2022.22:304. https://doi.org/10.1186/s12913-022-07663-6
- Reblozyl® package insert. Accessed 27 January https://packageinserts.bms.com/pi/pi_reblozyl.pdf
- Zynteglo® package insert. Accessed 27 January 2023. https://www.bluebirdbio.com/-/media/bluebirdbio/Corporate%20COM/Files/Zynteglo/ZYNTEGLO_prescribing_information.pdf
