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Advice: treat SF3B1-mutated MDS as distinct subtype

May 2020 Science Marjolein Groot

An international working group consisting of experts in myelodysplastic syndrome (MDS) have proposed to acknowledge a new subtype of MDS.1 Until now, the only MDS subtype that is characterised by a genetic abnormality was MDS with isolated del(5q). The newly proposed MDS-subtype is distinguished by a somatic mutation in the SF3B1-gene. The SF3B1-mutation is characterised by ring sideroblasts (erythroblasts with iron-loaded mitochondria), ineffective erythropoiesis and an indolent clinical course.

SF3B1-mutation

Approximately half of MDS-patients carries a somatic mutation in a spliceosome-gene. The SF3B1-mutation is the most common type of these mutations and is seen in  ~20% of MDS-patients. SF3B1-MDS patients could benefit from treatment that is geared towards their specific MDS0subtype. Patients with mutated SF3B1 often show a relatively good prognosis, because of a less aggressive form of the illness, compared to other MDS-patients.

Criteria SF3B1-MDS

The experts determined 4 diagnostic criteria for SF3B1-mutated MDS:

  1. Cytopenia as defined by standard hematologic values.
  2. Presence of a somatic SF3B1-mutation
  3. Morphologic dysplasia with or without ring sideroblasts
  4. Bone marrow blasts <5% and peripheral blood blasts <1%.

In the future, it might become possible to diagnose SF3B1-MDS based solely on the genetic mutation. This would take away the necessity to analyse the bone marrow for diagnosis.

Luspatercept

Determining the specific MDS-subtype of a patient is important to choose the best treatment for them. For SF3B1-mutated MDS-patients, luspatercept seems to be a promising medicine. Early 2020, a phase II study in which luspatercept was deployed by Fenaux et a was published in the New England Journal of Medicine.2

In this double-blinded, placebo-controlled study, MDS patients with the risk profile ‘very-low’, ‘low’ and ‘intermediate (following IPSS-R guidelines) and anaemia received the medicine luspatercept. This treatment with luspatercept led to a decrease in anaemia and transfusion need. Ninety-three percent of these luspatercept-treated patient was a carrier of the SF3B1-mutation. Luspatercept was approved on April 3th 2020 by the FDA for treating anaemia in the researched MDS patient population.3

References

1. Malcovati L, Stevenson K, Papaemmanuil E, et al. (2020). SF3B1-mutant myelodysplastic syndrome as a distinct disease subtype-A Proposal of the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM). Blood Journal, blood-2020004850.

2: Fenaux P, Platzbecker U, Mufti GJ, et al. (2020). Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. New England Journal of Medicine, 382(2), 140-151.

3. FDA.gov

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