New drugs for myeloid neoplasms with ring sideroblasts: Luspatercept vs imetelstat

Tefferi, Ayalew

doi:10.1002/ajh.26197

Cited by 8 publications

(14 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…53 The latter has led to the development of luspatercept, a recombinant activin receptor type IIB fusion protein that was designed to trap TGF-β superfamily ligands (including activin), for the treatment of anemia associated with transfusion-requiring beta thalassemia and low/intermediate-risk myelodysplastic syndromes with ring sideroblasts without (MDS-RS) or with (MDS-RS-T) thrombocytosis. 23,54,55 Luspatercept is currently undergoing a phase-3 study in transfusion-dependent patients with myelofibrosis on JAKi therapy (ClinicalTrials.gov Identifier: NCT04717414).…”

Section: Momelotinib: Mechanism(s) Of Actionmentioning

confidence: 99%

Momelotinib (JAK1/JAK2/ACVR1 inhibitor): mechanism of action, clinical trial reports, and therapeutic prospects beyond myelofibrosis

2023

Self Cite

View full text Add to dashboard Cite

Janus kinase 2 inhibitors (JAKi) are now part of the therapeutic armamentarium for primary and secondary myelofibrosis (MF). Patients with MF endure shortened survival and poor quality of life (QoL). Allogeneic stem cell transplant is currently the only treatment modality in MF with the potential to cure the disease or prolong survival. By contrast, current drug therapy in MF targets QoL and does not modify the natural history of the disease. The discovery of JAK2 and other JAK-STAT activating mutations (i.e., CALR and MPL) in myeloproliferative neoplasms, including MF, has facilitated the development of several JAKi that are not necessarily specific to the oncogenic mutations themselves but proved effective in countering JAK-STAT signaling, resulting in suppression of inflammatory cytokines and myeloproliferation. This non-specific activity resulted in clinically favorable effects on constitutional symptoms and splenomegaly and, consequently, FDA approval of three small molecule JAKi: ruxolitinib, fedratinib, and pacritinib. A fourth JAKi, momelotinib, is poised for FDA approval soon and has been shown to provide additional benefit in alleviating transfusiondependent anemia in MF. The salutary effect of momelotinib on anemia has been attributed to inhibition of activin A receptor, type 1 (ACVR1) and recent information suggests similar effect from pacritinib. ACRV1 mediates SMAD2/3 signalling that contributes to upregulation of hepcidin production and iron-restricted erythropoiesis. Therapeutic targeting of ACRV1 raises therapeutic prospects in other myeloid neoplasms associated with ineffective erythropoiesis, such as myelodysplastic syndromes with ring sideroblasts or SF3B1 mutation, especially those with co-expression of JAK2 mutation and thrombocytosis.

show abstract

Section: Momelotinib: Mechanism(s) Of Actionmentioning

confidence: 99%

Momelotinib (JAK1/JAK2/ACVR1 inhibitor): mechanism of action, clinical trial reports, and therapeutic prospects beyond myelofibrosis

2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…12 In regards to our observation on the association between luspatercept-induced anemia response and higher serum Epo level, it is tempting to speculate that serum Epo level in MDS-RS directly correlates with the degree of ineffective erythropoiesis, and thus identifies patients who are more likely to respond to drugs targeting ineffective erythropoiesis. Regardless, current deficit in terms of effective anti-anemia drugs in low-risk MDS, including MDS-RS, underscores an unmet need that might be addressed faster by targeting the underlying neoplastic clone 7,13,14 rather than the associated ineffective erythropoiesis. 15,16 The latter approach has proven more successful in anemias associated with beta-thalassemia.…”

Section: Real-world Experience With Luspatercept and Predictors Of Re...mentioning

confidence: 99%

Real‐world experience with luspatercept and predictors of response in myelodysplastic syndromes with ring sideroblasts

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, sideroblastic anemias combine various disorders characterized by iron overload and impaired heme biosynthesis. The occurrence of new therapeutic strategies using Luspacercept for the treatment argues for a rigorous assessment of RS [ 39 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

When Ring Sideroblasts on Bone Marrow Smears Are Inconsistent with the Diagnosis of Myelodysplastic Neoplasms

et al. 2022

View full text Add to dashboard Cite

Ring sideroblasts are commonly seen in myelodysplastic neoplasms and are a key condition for identifying distinct entities of myelodysplastic neoplasms according to the WHO classification. However, the presence of ring sideroblasts is not exclusive to myelodysplastic neoplasms. Ring sideroblasts are as well either encountered in non-clonal secondary acquired disorders, such as exposure to toxic substances, drug/medicine, copper deficiency, zinc overload, lead poison, or hereditary sideroblastic anemias related to X-linked, autosomal, or mitochondrial mutations. This review article will discuss diseases associated with ring sideroblasts outside the context of myelodysplastic neoplasms. Knowledge of the differential diagnoses characterized by the presence of ring sideroblasts in bone marrow is essential to prevent any misdiagnosis, which leads to delayed diagnosis and subsequent management of patients that differ in the different forms of sideroblastic anemia.

show abstract

New drugs for myeloid neoplasms with ring sideroblasts: Luspatercept vs imetelstat

Cited by 8 publications

References 25 publications

Momelotinib (JAK1/JAK2/ACVR1 inhibitor): mechanism of action, clinical trial reports, and therapeutic prospects beyond myelofibrosis

Momelotinib (JAK1/JAK2/ACVR1 inhibitor): mechanism of action, clinical trial reports, and therapeutic prospects beyond myelofibrosis

Real‐world experience with luspatercept and predictors of response in myelodysplastic syndromes with ring sideroblasts

When Ring Sideroblasts on Bone Marrow Smears Are Inconsistent with the Diagnosis of Myelodysplastic Neoplasms

Contact Info

Product

Resources

About