Luspatercept effective for myelofibrosis-associated anaemia

Prof. Aaron Gerds (Cleveland Clinic Taussig Cancer Institute, USA) presented the preliminary results of an ongoing, open-label, phase 2 trial, which evaluated whether anaemia resulting from myelofibrosis (MF) could be effectively treated with erythroid maturation agent luspatercept [1].

In this ongoing trial, patients (n=74) with MF and anaemia received luspatercept at 21-day intervals. Based on their red blood cell transfusion-dependent status at baseline, patients were allocated to 4 cohorts, also taking into account whether or not they had been receiving treatment with ruxolitinib at the start of the study.

Cohort 1 (n=20) included non-transfusion dependent (NTD) participants who had not received ruxolitinib treatment, and Cohort 2 (n=21) included transfusion-dependent (TD) participants, also without ruxolitinib. For patients who had received ruxolitinib, Cohort 3A (n=14) were NTD, and Cohort 3B patients (n=19) were TD. The primary endpoint was a ≥33% reduction in transfusion burden, with a ≥2-fold reduction in red blood cell units required during weeks 13-24 when compared with the initial 12-week baseline period.

Of the patients who received luspatercept, 21.4% reached the primary endpoint as opposed to only 4.5% who had received placebo (95% CI 10.4-23.6; P<0.0001). In the intent-to-treat analysis, the percentages of NTD patients who showed a consistent haemoglobin improvement of ≥1.5 g/dL above baseline at each evaluation for 12 consecutive weeks were 10% in Cohort 1 and 21% in Cohort 3A. Of patients who were initially TD, 32% in Cohort 3B demonstrated transfusion independence for ≥12 consecutive weeks as compared with 10% of Cohort 2. A mean haemoglobin increase of ≥1.5 g/dL was reported for 57% of Cohort 3A participants and 15% of Cohort 1 participants. A >50% reduction in transfusion burden was experienced by 38% of Cohort 2 patients and 53% of Cohort 3B patients.

Grade 3 or 4 treatment-related adverse events were observed in 5% of patients, but no treatment-related deaths occurred. In conclusion, luspatercept was safe and modestly effective at treating anaemia associated with MF.

1. Gerds A, et al. Abstract 557, ASH 2019, 7-10 December, Orlando, USA.

Posted on 5 March 20205 September 2024