Post-Approval Utilization of Pacritinib and Momelotinib in Patients with Myelofibrosis and Analysis of Early Treatment Outcomes
Authors: DiGennaro Jeremy V. , Concepcion George , Al Ali Najla H. , Chan Onyee , Walker Alison R. , Xie Zhuoer , Padron Eric , Lancet Jeffrey E , Sallman David , Kishtagari Ashwin , Vachhani Pankit , Mascarenhas John O. , Komrokji Rami S. , Kuykendall Andrew T. 
Published: December 2024

Introduction
Pacritinib (PAC) and momelotinib (MMB) have recently been approved for myelofibrosis (MF). Both agents target patients with cytopenic MF, with PAC approved for platelets &lt; 50 x 109/L and MMB for patients with MF and anemia. There is sizable overlap in efficacy profiles as both show the ability to improve spleen volume and disease-related symptoms while favorably impacting anemia and thrombocytopenia in a subset of patients. Optimal selection of PAC or MMB in cytopenic MF has not been well-defined. Direct comparison within the context of a clinical trial is lacking. Therefore, we analyzed patients treated with PAC and/or MMB since their respective FDA-approvals to characterize the profiles with each agent, early impact on hematologic values, and the overall outcomes.
Methods
We analyzed the first 50 patients who were treated at Moffitt Cancer Center with PAC or MMB. Treatment history, demographic, hematologic, and genetic information was obtained. Hematologic values and transfusion requirements were assessed every 3 months (+/- 1 month). Baseline values, change in blood counts over time, and treatment duration was compared between PAC and MMB-treated patients. T-tests and chi-square analysis were utilized for statistical analyses.
Results
Among 50 patients who received commercial PAC and/or MMB, 32 received MMB, 27 received PAC and 9 received both.
At baseline, patients receiving PAC had a median age of 77 years (y), median disease duration of 3.7 y, and received a median of 2.5 prior lines of therapy. High-risk mutations (HMR) were present in 14/27 (52%). MMB-treated patients had a median age of 75.5 y, median disease duration of 6.5 y, and a median of 2 prior lines of therapy. HMR were present in 15/32 (47%) patients. None of these variables were significantly different between the two agents.
At baseline, PAC-treated patients had median hemoglobin (hgb) and platelet (plt) count of 8.5g/dL (6.9-12.9g/dL) and 65 x 109/L (18-441 x 109/L), respectively. 8/27 (30%) were transfusion dependent (≥4 units RBCs/prior 8 weeks), 18/27 (67%) were transfusion-requiring with an average of 2.4 units/month. 21/27 (78%) had splenomegaly with median spleen length below left costal margin (LCM) of 7.5 cm. MMB-treated patients had baseline hgb and plt count of 8.7 g/dL (6.5-1.2 g/dL) and 141 x 109/L (15-504 x 109/L), respectively. 7/32 (22%) were transfusion-dependent, 19/32 (59%) were transfusion-requiring with an average of 1.9 units/month. 23/32 (75%) had splenomegaly with median spleen length below the LCM of 6 cm. PAC-treated patients had significantly lower baseline plt count than MMB-treated patients (p = 0.04).
8 patients (30%) treated with PAC had hematologic values at 3 months (mo). At this time, median hgb and plt count was 9.1 g/dL and 31 x 109/L, respectively. Average transfusion requirements decreased to 0.75 units/month. 23 (72%) patients treated with MMB had hematologic values at 3 mo. At this time hgb and plt count was 9.0 g/dL and 116 x 109/L. Average transfusion requirements decreased to 0.47 units/month.
In patients treated with MMB, hgb increase from baseline to 3 mo was more marked in those patients who were transitioning from ruxolitinib to MMB compared to patients with no recent ruxolitinib use (≤ 2 mo prior to MMB) (Δhgb 1.42 g/dL vs. 0.42 g/dL).
Median duration of treatment with PAC was 3.3 mo. Common reasons for discontinuation were GI toxicity (n = 7) and death (n = 6). Median duration of treatment with MMB was 8.2 mo. Common reasons for discontinuation were non-heme/non-GI toxicity (n = 7) and thrombocytopenia (n = 3). Differences in duration of treatment with PAC and did not reach statistical significance (p = 0.07).
Overall survival (OS) was longer in MMB-treated patients compared to PAC-treated patients with 6-month / 9-month OS of 73% / 64% with PAC vs. 96% / 96% with MMB (p = 0.037).
Conclusions
PAC and MMB are used in overlapping, high-risk patient populations. These patients are typically older, with extended disease duration, multiple prior lines of therapy, high-risk mutations, and have significant cytopenias. As expected, PAC-treated patients had more prominent baseline thrombocytopenia. Favorable impacts on anemia and transfusion requirements were shown with both PAC and MMB though long-term follow-up is limited. Ongoing evaluation in a large, multi-center, real world database of PAC and MMB-treated patients may help optimize treatment selection in patients with cytopenic MF.