5-Year Follow-Up Suggests Luspatercept Safely Reduces Anemia in Patients With Lower-Risk Myelodysplastic Syndromes


A significant portion of patients with lower-risk myelodysplastic syndromes achieved red-blood transfusion independence with luspatercept with no new safety signals.

Uwe Platzbecker, MD

Uwe Platzbecker, MD

Luspatercept (Reblozyl) was associated with a favorable safety profile and long-term efficacy in patients with untreated lower-risk myelodysplastic syndromes (LR-MDS), regardless of subtype, according to a 5-year follow-up of the phase 2 PACE MDS study (NCT01749514/NCT02268383), results of which were recently published in the Journal of Clinical Oncology.1

Overall, the rates of treatment-emergent adverse events (TEAEs) in the ring sideroblasts (RS) group (n = 62) and non-RS group (n = 44) were (48.4%) and (36.4%), respectively (P = .11). In the RS group, the most common TEAEs were fatigue (9.7%), hypertension (6.5%), and diarrhea (6.5%), whereases, in the non-RS group, headache (11.4%), hypertension (6.8%), and bone pain (6.8%) were the most frequent symptoms.

Only 1 patient with RS had disease progression to acute myeloid leukemia, confirming the overall safety of luspatercept exposure of 2 years or greater, according to study authors.

Additionally, over a quarter of patients without RS achieved 8 weeks or more of transfusion independence, and over a third of patients with untreated non-RS achieved a hematologic improvement erythroid response.

“Luspatercept demonstrated long-term clinical efficacy and safety comparable with previous reports, in patients with LR-MDS irrespective of subtype, particularly in untreated patients,” Uwe Platzbecker, MD, director of the Medical Clinic at the University Hospital in Leipzig, and co-investigators wrote.

Patients with MDS experience ineffective erythropoiesis, meaning that they struggle to produce sufficient red blood cells. Consequently, reducing the transfusion burden and anemia symptoms in patients with lower-risk MDS are considered key aspects of care.

Luspatercept binds transforming growth factor-B superfamily ligands, thus diminishing Smad2/3 signaling and encouraging late-stage erythropoiesis. In the phase 2, multicenter, PACE-MDS trial, patients with LR-MDS, both with and without RS, transfusion burdens, and proper treatment with erythropoiesis-stimulating agent were enrolled to receive the agent.

In the phase 3 MEDALIST trial (NCT02631070), the agent yielded promising efficacy in reducing transfusion burden among these patients, inspiring the 2020 approval of luspatercept for the treatment of anemia in patients with MDS and RS.2 However, since between 70% and 80% of patients with MDS do not have RS, there is an unmet need for this patient population—particularly after failure with previous erythropoiesis-stimulating treatments.1

Study authors noted that the sample size was small, yet the positive results call for further investigation.

In the RS cohort, 22 out of 42 patients (52.4%) achieved red-blood cell (RBC) transfusion independence for greater than 8 weeks (P = .139); in the non-RS cohort, 10 out of 29 patients achieved RBC transfusion independence (34.5%; P = .139). In addition, 43.8% of patients classified as transfusion dependent experienced 8 weeks or more of RBC-transfusion independence.

Moreover, among patients with a low transfusion burden (TB), 71.4% (n = 20/28) achieved RBC-transfusion independence of 8 weeks of greater, and among patients with a high TB, the rate was 46.9% (15/31); 51.6% among those with SF3B1 and SF3B1 mutations (P = .710), respectively, and 76.9% (n = 10/13) for those with non-SF3B1 splicing factor mutations (P = .026) and 5 of 19 patients (23.6%) with no splicing factor mutations (P = .018).

A total of 53.7% of patients (n = 58/108) achieved the International Working Group–defined hematologic improvement erythroid response. The rates of improvement among those who 67.7%, 36.4%, 70.6%, and 89.5% among those who had RS (n = 62), those without RS (n = 44), among untreated patients (n = 34), and untreated with confirmed RS (n = 19), respectively.

The ongoing COMMANDS trial (NCT03682536) will further explore how luspatercept elicited promising hematologic improvement erythroid in the untreated non-RS patient population.


  1. Platzbecker U, Götze KS, Kiewe P, et al. Long-term efficacy and safety of luspatercept for anemia treatment in patients with lower-risk myelodysplastic syndromes: the phase II PACE-MDS study. J Clin Oncol. Published online August 23, 2022. doi:10.1200/JCO.21.02476
  2. FDA approves luspatercept-aamt for anemia in adults with MDS. FDA. Updated April 6, 2022. Accessed September 29, 2022. bit.ly/391vXSy

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