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Personalising treatment for sickle cell disease

Presented by
Dr Erfan Nur, Amsterdam University Medical Center, the Netherlands
EHA 2021
Sickle cell disease (SCD) includes various inherited red blood cell disorders, calling for a variety of treatment approaches. To achieve the optimal treatment for each SCD patient, physicians should consider patient-related factors in combination with available treatment options.

Dr Erfan Nur (Amsterdam University Medical Center, the Netherlands) discussed personalised treatment options and their importance for patients with SCD [1]. Each SCD patient has a unique set of factors to consider in the treatment decision process: genotype (e.g. haemoglobin [Hb]SS, HbSC, HbSβ0, HbSβ+), disease burden (relative contribution of pathophysiologies: vaso-occlusion, haemolytic anaemia), complications (e.g. acute coronary syndrome, stroke, splenic sequestration), treatment factors (e.g. efficacy, side effects, availability, clinical trial eligibility), care network (level of access), and impact on daily and social life.

Before 2017, treatment and management options for SCD were limited to blood transfusions, dietary supplements, haematopoietic stem cell transplant (HSCT), hydroxyurea (HU), alternative management (e.g. rest, hydration), analgesics, and dietary supplements. Potential limitations of these therapies are adverse events, limited availability, and in some cases limited efficacy [2].

For example, blood transfusion treatment showed a 92% reduction of stroke risk versus placebo in the STOP trial (NCT00006182). Active transfusions are performed in emergency situations whereas chronic transfusions are, for instance, performed to prevent cerebrovascular disease or frequent pain episodes [3]. However, transfusions have potential long-term complications, including iron overload, red blood cell allo-immunisation, and delayed haemolytic reactions.

So far, HSCT is the only potentially curative treatment, but it also has several limitations. Only 18% of patients have a matched sibling donor and are eligible for this treatment. There are two types of HSCT treatment: myeloablative and non-myeloablative conditioning. The latter is associated with reduced transplant-related complications, such as reduced toxicity, but leads to higher graft failure rates [4].

HU was one of the earliest promising drugs in SCD and is, to date, the mainstay of SCD therapy in adults [5]. HU increases Hb levels, resulting in a reduced annual rate of vaso-occlusive crises (VOCs), reduced frequency of pain crises, and a reduction in stroke risk. However, not all patients obtain a response and adherence to therapy remains an issue [6]. Since 2017, HU is also approved for children. Paediatric studies in SCD show similar safety of HU as in adults, providing an invaluable resource to prevent organ damage in children.

Over the past years, new treatment options have become available or are in clinical development, such as L-glutamine (an antioxidant), crizanlizumab (an anti-P-selectin monoclonal antibody), and voxelotor (a sickled haemoglobin polymerisation inhibitor) [2]. L-glutamine reduced the VOC frequency by 25% and hospitalisation by 33% versus placebo [7]. Crizanlizumab significantly reduced the annual rate of VOCs by 45% compared with placebo, demonstrated a longer time to first VOC, and little risk for immunogenicity and hypersensitivity reactions [8]. Voxelotor reduced levels of haemolysis markers and increased Hb levels and reduced the annualised incident rate of VOCs [9]. Gene therapies are also under investigation, including LentiGlobin, CTX001, OTQ923, and HIX763.

Dr Nur concluded, “consideration of treatment options must be in the context of specific patient-related factors to come to a personalised treatment decision”.

    1. Nur E. Knowing the options: personalizing treatment of SCD. 1UiHSAT-SL3, EHA 2021 Virtual Congress, 9–17 June.
    2. Cisneros GS and Thein SL. Front Physiol 2020;11:435.
    3. Adams RJ, et al. N Engl J Med 1998;339:5–11.
    4. Nur E, et al. HemaSphere 2019;3(S1):1027–8.
    5. Yasara N, et al. Orphanet J Rare Dis 2021;16:114.
    6. Thornburg CD, et al. Blood 2012;120(22):4304–10.
    7. Niihara Y, et al. BMC Blood Disord 2005;5:4.
    8. Ataga KI, et al. N Engl J Med 2017;376:429–39.
    9. Howard J, et al. HemaSphere 2020;4(S1)EP1540:714.


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