Final Results of a Phase 2 Study of Sotatercept (ACE-011) for Anemia of MPN-Associated Myelofibrosis

Bose, Prithviraj; Masárová, Lucia; Pemmaraju, Naveen; Bledsoe, Sharon D.; Daver, Naval; Jabbour, Elias; Kadia, Tapan M.; Estrov, Zeev; Kornblau, Steven M.; Andreeff, Michael; Cortés, Jorge E.; Jain, Nitin; Borthakur, Gautam; Alvarado, Yesid; Huynh-Lu, Julie; Nguyen-Cao, Madeleine; Richie, Mary Ann; Dobbins, Mackenzie H.; McCrackin, Selene Andrea; Zhou, Lingsha; Pierce, Sherry; Wang, Xuemei; Pike, Allison; Kantarjian, Hagop; Verstovšek, Srđan

doi:10.1182/blood-2021-150908

Cited by 11 publications

(6 citation statements)

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“…Hence, there is growing interest in finding innovative targets to improve anemia in MF. New molecules targeting the TGF-beta superfamily, such as luspatercept and sotatercept, are under investigation alone or combined with RUX [23,24,39]. The former is already recommended by the National Comprehensive Cancer Network (NCCN) guidelines for MF patients with anemia [40].…”

Section: Discussionmentioning

confidence: 99%

Incidence of blast phase in myelofibrosis according to anemia severity

Mora

Maffioli

Rumi

et al. 2023

eJHaem

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Myelofibrosis (MF) is a clonal malignancy frequently characterized by anemia and in 10%–20% of cases it can evolve into blast phase (BP). Anemia in MF is associated with reduced survival and ‐in primary MF‐ also with an increased probability of BP. Conventional treatments for anemia have limited effectiveness in MF.Within a dataset of 1752 MF subjects largely unexposed to ruxolitinib (RUX), BP incidence was 2.5% patients per year (p‐y). This rate reached respectively 4.3% and 4.5% p‐y in case of patients with common terminology criteria for adverse events (CTCAE) grade 3/4 and grade 2 anemia, respectively, that represented together 32% of the cohort. Among 273 MF cases treated with RUX, BP incidence was 2.89% p‐y and it reached 4.86% p‐y in subjects who started RUX with CTCAE grade 2 anemia (one third of total). Within patients with red blood cell transfusion‐dependency at 6 months of RUX (21% of the exposed), BP rate was 4.2% p‐y. Our study highlights a relevant incidence of BP in anemic MF patients, with a similar rate whether treated with or without RUX. These findings will help treating physicians to make decisions on the safety profile of innovative anemia treatments.

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Section: Discussionmentioning

confidence: 99%

Incidence of blast phase in myelofibrosis according to anemia severity

Mora

Maffioli

Rumi

et al. 2023

eJHaem

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“…The other TGF-β inhib i tors luspatercept and sotatercept have elicited ane mia improve ments in patients with MF (Table 2). 48,49 An ongo ing random ized phase 3 study is assessing luspatercept com pared to pla cebo in patients with MF on Jak inhib i tor ther apy who require trans fu sions (NCT04717414).…”

Section: Discussionmentioning

confidence: 99%

New approaches to tackle cytopenic myelofibrosis

Reynolds

Pettit

2022

Hematology

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Myelofibrosis (MF) is a clonal hematopoietic stem cell neoplasm characterized by constitutional symptoms, splenomegaly, and risks of marrow failure or leukemic transformation and is universally driven by Jak/STAT pathway activation. Despite sharing this pathogenic feature, MF disease behavior can vary widely. MF can generally be categorized into 2 distinct subgroups based on clinical phenotype: proliferative MF and cytopenic (myelodepletive) MF. Compared to proliferative phenotypes, cytopenic MF is characterized by lower blood counts (specifically anemia and thrombocytopenia), more frequent additional somatic mutations outside the Jak/STAT pathway, and a worse prognosis. Cytopenic MF presents unique therapeutic challenges. The first approved Jak inhibitors, ruxolitinib and fedratinib, can both improve constitutional symptoms and splenomegaly but carry on-target risks of worsening anemia and thrombocytopenia, limiting their use in patients with cytopenic MF. Supportive care measures that aim to improve anemia or thrombocytopenia are often ineffective. Fortunately, new treatment strategies for cytopenic MF are on the horizon. Pacritinib, selective Jak2 inhibitor, was approved in 2022 to treat patients with symptomatic MF and a platelet count lower than 50 × 109/L. Several other Jak inhibitors are in development to extend therapeutic benefits to those with either anemia or thrombocytopenia. While many other novel non–Jak inhibitor therapies are in development for MF, most carry a risk of hematologic toxicities and often exclude patients with baseline thrombocytopenia. As a result, significant unmet needs remain for cytopenic MF. Here, we discuss clinical implications of the cytopenic MF phenotype and present existing and future strategies to tackle this challenging disease.

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“…The author read and approved the final manuscript. Imetelstat II [31] Pembrolizumab II [32] Nivolumab II [33] Sotatercept II [34]…”

Section: Discussionmentioning

confidence: 99%

“…TGF− was found to be significantly expressed in the bone marrow of MF patients, and it is thought to have a role in the fibrosis caused by the disease. Sotatercept was proven to be safe and effective in treating anaemia in MF patients in phase II studies [34].…”

Section: Non-jak Targeted Drugs For Myelofibrosismentioning

confidence: 99%

Myelofibrosis treatment history and future prospects

Ghit

2022

Egypt J Intern Med

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Myelofibrosis (MF) is a haematopoietic stem cell tumour caused by the lack of BCR-ABL translocation due to point mutations in Janus kinases (JAKs). In previous years, dealing with MF included several protocols such as traditional drugs that control general symptoms, splenectomy, blood transfusion, and allogeneic haematopoietic stem-cell transplantation (HSCT). Allogeneic HSCT is remaining the only treatment that has the potential to alter MF’s progression. However, clinical trials of JAK inhibitors and non-JAK targeted therapies have been increasingly carried out in earlier years. The most prominent JAK inhibitors for the treatment of MF are ruxolitinib, fedratinib, momelotinib, pacritinib, gandotinib, ilginatinib, itacitinib, and lestaurtinib. On the other hand, the non-JAK targeted therapies that showed strong efficacy and safety are alisertib, imetelstat, pembrolizumab, nivolumab, and sotatercept. In this review, we summarized the recent clinical trials carried out on these drugs to understand their efficacy and safety. Also, we talked briefly about allogeneic HSCT as powerful therapy until the present for patients suffering from MF.

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Final Results of a Phase 2 Study of Sotatercept (ACE-011) for Anemia of MPN-Associated Myelofibrosis

Cited by 11 publications

References 0 publications

Incidence of blast phase in myelofibrosis according to anemia severity

Incidence of blast phase in myelofibrosis according to anemia severity

New approaches to tackle cytopenic myelofibrosis

Myelofibrosis treatment history and future prospects

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