Transfusion Independence Confirmed as Clinically Relevant for Survival in Myelofibrosis

Among patients with anemia related to myelofibrosis, red blood cell (RBC) transfusion status may have an effect on survival, according to a post-hoc pooled analysis of three phase III trials of the JAK1/JAK2/ACVR1 inhibitor momelotinib.

Specifically, when researchers accounted for differences in known prognostic factors, effect modifiers, and changes in RBC transfusion status, they found that independence from RBC transfusion was an independent predictor of survival, according to Vikas Gupta, MD, of the Princess Margaret Cancer Centre in Toronto, Canada.

Dr. Gupta and colleagues conducted a post-hoc time-dependent analysis of the phase III Simplify-1 (JAK inhibitor naïve), Simplify-2 (JAK inhibitor exposed), and MOMENTUM (JAK inhibitor exposed) trials, which all studied momelotinib versus an active comparator. These analyses were performed on patients included in the studies’ safety populations. Several factors were examined for prognostic impact.

In the Simplify-1 trial, age (P<.0001), platelet count (P=.0109), RBC transfusion status, and baseline spleen volume (P=.0015) were significantly associated with overall survival (OS). In Simplify-2, age (P=.0020), RBC transfusion status, baseline spleen volume (P=.0002), and Dynamic International Prognostic Scoring System score were all significantly associated with OS. In MOMENTUM, only RBC transfusion status was associated with survival.

In the MOMENTUM trial, after the researchers accounted for differences in prognostic factors and effect modifiers, as well as changes in transfusion status over time, transfusion independence had a strong relationship with OS (hazard ratio [HR]=5.18; 95% CI, 1.86-14.47; P=.0017). According to the researchers, this translated to a more than fivefold greater risk for all-cause mortality among patients who were not transfusion independent.

Transfusion independence was also associated with improved overall survival in Simplify-1 (HR=3.32; 95% CI, 2.31-4.78; P<.0001) and Simplify-2 (HR=1.87; 95% CI, 1.07-3.29; P=.0287).

“These data validate transfusion independence status as a clinically relevant and meaningful endpoint that is prognostic for survival in JAK inhibitor–naïve and JAK inhibitor–experienced disease settings,” the researchers concluded.

Reference

Gupta V, Harrrison C, Gorsh B, et al. Comparison of the enzymatic and cellular profiles of clinical JAK2 inhibitors for the treatment of myelofibrosis. Abstract #3188. Presented at the 65th ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, California.