Orlando, Florida—Initial results from an ongoing study presented at the ASH Annual Meeting suggest clinically significant activity of luspatercept for the treatment of myelofibrosis-associated anemia.

“Approximately two-thirds of patients with primary or post-essential thrombocythemia/ polycythemia vera myelofibrosis…have anemia, many of whom require red blood cell (RBC) transfusions. In this heavily transfused population, there are severely limited treatment options; effective treatment for anemia in MF is a critically unmet medical need,” explained Aaron T. Gerds, MD, MS, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, and colleagues.

Because of this, Dr Gerds and coinvestigators conducted a phase 2 trial evaluating luspatercept, a first-in-class erythroid maturation agent, in this patient population.

A total of 74 patients with myelofibrosis and anemia were enrolled on the trial. Of which, 41 were not receiving concomitant ruxolitinib at study entry and received either no RBC transfusions (n=20; cohort 1) or 2-4 RBC transfusions in the 12 weeks prior to treatment (n=21; cohort 2). The remaining 33 patients were receiving a stable dose of ruxolitinib for ≥16 weeks. Of which 14 were not receiving RBC transfusions (cohort 3a) and 19 were (cohort 3b).

Luspatercept was administered every 21 days at a starting dose of 1.0 mg/kg in doses escalating up to 1.75 mg/kg.

The primary end point in patients who did not receive RBC transfusions was hemoglobin increase ≥1.5 g/L at every assessment from baseline for ≥12 consecutive weeks, within the first 24 weeks. The primary end point in patients receiving RBC transfusions was RBC transfusion-independence for ≥12 consecutive weeks, within the first 24 weeks.

Additional trial end points included the proportion of patients achieving mean hemoglobin increase ≥1.5 g/dL in Cohorts 1 and 3a, and ≥50% decrease in RBC transfusions (minimum 4 RBC U decrease from baseline) in Cohorts 2 and 3b, with both responses lasting ≥12 consecutive weeks, within 24 weeks on the study.

The median hemoglobin concentration at study entry was 8.8 g/dL (range, 6.7–9.8 g/dL) for Cohort 1 and 8.6 g/dL (range, 6.7–9.1 g/dL) for Cohort 3a. Patients in Cohort 2 received a median of 2.7 RBC U/28 days (range, 1–5 U/28 days) and patients in Cohort 3b received a median of 2.3 RBC U/28 days (range, 2–4 U/28 d). Patients received a median of 8 cycles of luspatercept (range, 1–24 cycles).

In Cohorts 1 and 3a, 2 of 20 (10%) and 3 of 14 (21%) patients, respectively, achieved an absolute hemoglobin increase ≥1.5 g/dL at every measurement from baseline over any consecutive 12 weeks. Additionally, in Cohorts 2 and 3b, 2 of 21 (10%) and 6 of 19 (32%) patients, respectively, achieved RBC transfusion independence over any consecutive 12 weeks.

The median duration of hemoglobin response was 20 weeks (range, 12–27 weeks) in Cohort 1 and 12 weeks (range, 12–13 weeks) in Cohort 3a. The median duration of RBC transfusion independence was 23 weeks (range, 16–31 weeks) in Cohort 2 and 32 weeks (range, 12–65 weeks) in Cohort 3b.

A total of 3 (15%) and 8 (57%) patients in Cohorts 1 and 3a, respectively, achieved a mean hemoglobin increase of ≥1.5 g/dL. Additionally, 8 (38%) and 10 (53%) patients in Cohorts 2 and 3b, respectively, achieved a ≥50% reduction in RBC transfusion burden from baseline.

Dr Gerds and colleagues noted that ruxolitinib exposure remained stable throughout the 24-week treatment period in both Cohorts 3a and 3b, and no difference in spleen size between responders and non-responders was observed.

Grade 3–4 treatment-related adverse events (AEs) were reported in 4 (5%) patients. No treatment-related deaths were reported.

The most common treatment-related AEs, occurring in ≥3% of patients, were hypertension (11%), bone pain (8%), and diarrhea (4%). A total of 7 (9%) patients had ≥1 AE resulting in treatment discontinuation; 23 (31%) patients remain on the study.

“The initial results from this ongoing study suggest clinically significant activity of luspatercept in patients with MF [myelofibrosis]-associated anemia, including those receiving concomitant ruxolitinib,” Dr Gerds and colleagues concluded.—Janelle Bradley

Gerds AT, Vannucchi AM, Passamonti F, et al. A Phase 2 Study of Luspatercept in Patients with Myelofibrosis-Associated Anemia. Presented at: the 2019 ASH Annual Meeting & Exposition; December 7-10, 2019; Orlando, FL. Abstract 557.