Abstract Introduction: PRM-151, a recombinant human pentraxin-2 molecule, has been shown to prevent and reverse fibrosis in animal models of myelofibrosis (MF) by postulated targeting differentiation of fibrocytes (essential cells in fibrotic process) from monocytes. In the first stage of a two-stage trial, 27 patients (pts) with primary myelofibrosis (PMF), post-essential thrombocythemia/polycythemia vera (post-ET/PV) MF, and Grade 2 or 3 bone marrow fibrosis (BMF) received PRM-151 10 mg/kg IV ± ruxolitinib (RUX) for 6 cycles (24 weeks). A reduction in BMF, decrease in symptoms (MPN-SAF Total Symptom Score [TSS]), and a reduction of palpable splenomegaly were observed, along with a favorable safety profile. Pts experiencing clinical benefit were allowed to continue beyond 24 weeks in an open label extension (OLE) study. Here, we report interim efficacy and safety data for 18 pts enrolled in the OLE, who had been treated for up to 35 cycles (140 weeks). Methods: All pts in the OLE received a monthly infusion of PRM-151 10 mg/kg IV. Pts receiving PRM-151 alone or in combination with RUX in the main study continued with their respective drugs. Safety and hematology parameters were assessed monthly, and MPN-SAF TSS Q3 months. BM biopsies were obtained at baseline, end of main study, and at physician discretion in the OLE. These were evaluated centrally by two independent, blinded hematopathologists for the degree of reticulin and collagen fibrosis. Immunostaining for fibrocytes was performed on available biopsies. The primary objective of the OLE was to assess safety and efficacy of long-term administration of PRM-151. Results: Of the 18 pts enrolled in the OLE, 9 received PRM-151 as single agent, and 9 in conjunction with RUX. Baseline characteristics included median age of 66 years (51-78); 8 pts were DIPSS Int-1, 9 Int-2, and 1 high-risk; 6 (33%) had Hgb < 100 g/L, 12 (67%) had PLT < 100 x 109/L; 7 (39%) had PLT <50 x 109/L; 8 pts had PMF, 10 had post-ET/PV MF; 13 pts (72%) had a palpable spleen, and 9 (50%) had Grade 3 BMF. Median time on study for these 18 pts was 30.9 months (15.9-47.2 months). All pts experienced at least 1 adverse event (AE), with 8 pts (44%) reporting a possible study drug-related AE. No unexpected AEs were observed, and no deaths were reported during the study period. The mean best percent change (by palpation) in spleen size from baseline was −37%, with a median percent reduction of −26.1% (Figure). The mean best percent improvement in MPN-SAF TSS was −54%, with a median percent reduction of TSS of −64%. Pts in the PRM-151 monotherapy group showed similar improvements in MPN-SAF TSS and splenomegaly as those receiving PRM-151 + RUX (Figure). Complete data on hematology parameters will be available at the time of presentation. Improvement in BM reticulin grade was observed in 5 of 7 pts (71%) with Grade 2 BMF at baseline, and in 4 of 9 pts (44%) with Grade 3 BMF at baseline. Of the pts with Grade 3 BMF at baseline, 2 of 9 pts (22%) had a 2-grade reduction (Table). In addition, 5 of 6 pts (83%) with Grade 2 collagen fibrosis at baseline had a 1-grade reduction, with 2 of 6 pts (33%) improving to Grade 0. Also, 2 of 7 pts (28%) with Grade 3 collagen fibrosis had a reduction of 1-grade with 1 of 7 (14%) improving to Grade 0 (Table). Eight of 18 pts had BM fibrocyte immunostaining done: mean fibrocyte count in the hematopoietic BM decreased from 378.0 ± 255.3 per mm2 (11.2 ± 7.7% of total cells) at study baseline to 81.3 ± 86.5 per mm2 (2.0 ± 2.1% of total cells; 7 of 8 pts evaluable) at cycle 25, with continuous reduction in fibrocyte numbers observed at interim. Over the same period, improvement in BM reticulin grade was detected in 4 of 7 pts (57%), and collagen fibrosis grade was decreased in 3 of 7 pts (43%). Conclusions: This long-term follow-up study of 18 pts with MF who received PRM-151 for a median of 31 months showed the drug to be well tolerated. An overall improvement in BM reticulin and collagen fibrosis grade, as well as reductions in MPN-SAF TSS and splenomegaly were observed. In a subset of pts for whom bone marrow fibrocyte immunostaining data were available, a mean reduction in fibrocyte counts was observed, as well as improved bone marrow reticulin and collagen fibrosis grade. These data warrant confirmation in a larger controlled study. Figure. Figure. Disclosures Verstovsek: Incyte: Consultancy; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees. Pozdnyakova:Promedior, Inc.: Consultancy. Mesa:Promedior: Research Funding; Incyte: Research Funding; Ariad: Consultancy; Novartis: Consultancy; Celgene: Research Funding; Galena: Consultancy; Gilead: Research Funding; CTI: Research Funding. Foltz:Incyte: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Mascarenhas:Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Roche: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Promedior: Research Funding. Ritchie:Astellas Pharma: Research Funding; NS Pharma: Research Funding; Pfizer: Consultancy, Research Funding; Bristol-Myers Squibb: Research Funding; ARIAD Pharmaceuticals: Speakers Bureau; Novartis: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding, Speakers Bureau; Celgene: Consultancy, Other: Travel, Accommodations, Expenses, Speakers Bureau; Incyte: Consultancy, Speakers Bureau. Palmer:Novartis: Research Funding. Kremyanskaya:Incyte: Research Funding. van den Blink:Promedior, Inc.: Employment. Gupta:Promedior, Inc.: Employment. Gotlib:Deciphera: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Kartos: Consultancy; Promedior: Research Funding; Gilead: Consultancy, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Blueprint Medicines: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.