Background Autoimmune haemolytic anaemia (AIHA) is a type of anaemia that develops when the antibodies of the immune system destroy some of the red blood cells,¹ causing haemolysis. The aetiology remains uncertain, but an increase in autoantibodies and lymphocytes in the presence of decreased immune tolerance is thought to be involved.²

A 2-year-old patient with adenosine deaminase deficient severe combined immunodeficiency (ADA-SCID) was diagnosed with AIHA post-gene therapy, which was not responsive to intravenous immunoglobulins (IVIG), corticosteroids and rituximab, and was initiated on sirolimus as a steroid-sparing agent.

One-year post-gene therapy, the patient continued to suffer from poor immune reconstitution. Due to multiple drug interactions, increasing hepato- and myelotoxicities and continuously fluctuating sirolimus levels, the patient was initiated on IV abatacept. The patient responded well to abatacept and sirolimus was gradually weaned off. However, on day 24 (D24), after completion of the initial loading course of abatacept, he went into an acute haemolytic crisis. The next schedule dose was rescheduled from D28 to D24, and IV bortezomib was initiated as a bridging agent and two doses given, while IV daratumumab was requested on a compassionate-use basis. Due to the difference in mechanisms of actions, these agents were pursued. However, the use of these drugs in paediatrics is limited.

Pharmacy Contributions The immunology pharmacists were heavily involved in the discussion of treatment options at several multi-disciplinary team (MDT) meetings. Once a consensus was reached, the pharmacists performed a comprehensive literature search to determine appropriate dosing regimens and assess risks versus benefits. Daratumumab was requested from the manufacturer on a compassionate-use basis, where the patient’s medical background, the urgent clinical need and rationale for this therapy was explained. Subsequently, the manufacturer agreed that the patient may benefit from daratumumab. Pharmacists ensured adequate supply of daratumumab was provided for the duration of therapy and that local governance processes were adhered to. The pharmacists explained the options appraisal to the family, including counselling of the safety and practical aspects of the drugs, the unlicensed and off-label nature, side effect profile, monitoring and the aim of the treatment. Patient information leaflets were also provided. During treatment with abatacept, bortezomib and daratumumab, the patient was closely monitored for drug-related adverse side effects.

Outcome As a result of multiple drug interactions and compounding thrombocytopenia in the clinical context of AIHA, the patient developed gastrointestinal bleeding following two doses of bortezomib. Approval of daratumumab was timely. Using a combination of agents which target different cells, the patient responded well and this enabled weaning of corticosteroids.

Lessons Learned Despite potentially serious side effects, the patient had a good response to abatacept and daratumumab in the management of AIHA. The management of this patient required extensive support from the entire MDT. The pharmacists’ understanding of the patients’ complex medical needs and pharmacokinetics helped obtain life-saving medicines that are rarely used in children. With all three medicines being off-license and off-label, clinical governance is of utmost importance.

References

1. National Institute for Health & Care Excellence (NICE). Rituximab for treating autoimmune haemolytic anaemia. February 2015.

2. Hess J, Su L, Nizzi F, et al. Successful treatment of severe refractory autoimmune hemolytic anemia after hematopoietic stem cell transplant with abatacept. Transfusion 2018;58:2122–2127.