Luspatercept, a two‐edged sword in beta‐thalassemia‐associated paravertebral extramedullary hematopoietic masses (EHMs)

Abstract

Paravertebral extramedullary hematopoietic masses (EHMs) account for up to 15% of extramedullary pseudotumors in beta‐thalassemia (BT) and are most likely related to compensatory hematopoiesis. In most cases, pseudotumors are incidentally detected, as the majority of patients are asymptomatic. Since June 2020, luspatercept is approved for the treatment of patients with BT who require regular red blood cell transfusions. Data addressing the safety and efficacy of luspatercept in patients with BT‐associated EHMs are pending. To date (May 2022), paravertebral EHMs were observed in two asymptomatic patients out of currently 43 adult patients with BT registered at the Adult Hemoglobinopathy Outpatient Unit of the University Hospital Essen, Germany. In one of them, a paravertebral EHM was diagnosed more than 10 years prior to referral. Throughout observation time, treatment with luspatercept was associated with a clinically significant reduction in transfusion burden while allowing to maintain a baseline hemoglobin concentration of ≥10 g/dL aiming to suppress endogenous (ineffective) erythropoiesis associated with BT. Considering the rarity of paravertebral EHMs in BT, luspatercept might potentially represent a novel therapeutic option for these often‐serious disease‐associated complications. However, appropriate follow‐up investigations are recommended to detect (early) treatment failures secondary to an undesired luspatercept‐associated erythroid expansion.

Treating Thalassemia Patients with Luspatercept: An Expert Opinion Based on Current Evidence

“…There is currently no definitive evidence in the literature on the effect of luspatercept on extramedullary erythropoiesis. Both cases of improvement and worsening of the masses have been anecdotally reported [ 12 ].…”

Cardiac complications in thalassemia throughout the lifespan: Victories and challenges

“…The activin‐trap inhibitor, luspatercept, facilitates the stability of endogenously produced red blood cells in patients with thalassemia major, leading to significant reductions of transfusion volume in some patients 77 . However, subsequent lowering of transfusion volume has been associated with extramedullary erythropoiesis in some, 78 suggesting released suppression of ineffective erythropoiesis.…”

Luspatercept: A New Tool for the Treatment of Anemia Related to β-Thalassemia, Myelodysplastic Syndromes and Primary Myelofibrosis

“…The role of luspatercept on extramedullary hematopoiesis needs to be further explored, since the data are limited and conflicting. There is one case of recurrent spinal cord compression due to an extramedullary hematopoietic mass (EHM) in a thalassemic patient on luspatercept that was ultimately treated with radiotherapy [ 44 ]; one case of a TD patient that achieved transfusion independence with a later asymptomatic increase of the EHM and another case with a >50% reduction in the transfusion burden and stable EHM [ 45 ]. As the authors suggest, luspatercept might be a new therapeutic option for these patients, by improving ineffective erythropoiesis and decreasing the need for transfusions; on the other hand, patients need to be monitored closely and discontinue treatment if they do not respond in order to avoid undesired erythroid expansion [ 45 ].…”