- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Journal: Ineffective erythropoiesis and its treatment. (Pubmed Central) - Dec 22, 2021
Luspatercept is also approved for the treatment of transfusion-dependent anemia in patients with MDS with ring sideroblasts, most of whom carry a somatic SF3B1mutation. While long-term efficacy and safety of luspatercept need to be evaluated both in β-thalassemia and MDS, defining the molecular mechanisms of ineffective erythropoiesis in different disorders might allow the discovery of new effective compounds.
- |||||||||| azacitidine / Generic mfg.
Journal: Advances in myelodysplastic syndrome. (Pubmed Central) - Nov 29, 2021
We also provide commentary on the future of therapeutic development in myelofibrosis. Better diagnosis and prognostic stratification may allow a more precise and personalized treatment of MDS with novel agent combinations leading to improved therapeutic algorithms.
- |||||||||| lenalidomide / Generic mfg., danazol oral / Generic mfg.
Clinical, P3 data, Review, Journal: Management of Myelofibrosis-Associated Anemia: Focus on Standard Agents and Novel Therapeutics in Phase 3 Clinical Trials. (Pubmed Central) - Nov 29, 2021
While clinical trials are advised, not all patients have convenient access, and therefore, hematologists should be aware of the data supporting the use of conventional agents such as erythropoietin-stimulating agents, steroid treatments (danazol and prednisone), and immunomodulatory drugs (thalidomide and lenalidomide)...Luspatercept promotes late-stage hematopoiesis, and the phase 2 study has shown promise in ameliorating anemia as a monotherapy, and especially in combination with ruxolitinib...Safety and effectiveness are reviewed for both conventional and selected novel agents used in the treatment of MF-anemia. A practical approach to treatment is presented, and data from ASH 2020 are presented.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Luspatercept in MDS () - Nov 27, 2021 - Abstract #EHOC2021EHOC_228;
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Lower-Risk Myelodysplastic Syndromes: Erythropoiesis-Stimulating Agent Treatment Approaches and Outcomes in the United States () - Nov 24, 2021 - Abstract #ASH2021ASH_6123;
Eligible patients had ≥ 1 year of follow-up after diagnosis (unless the patient died during this time) and did not receive luspatercept or any MDS treatment as part of a randomized, controlled trial...Nearly one-fifth of patients in this study treated with an ESA were considered to have failed ESA treatment by abstracting physicians, though this proportion is likely to be higher with extended follow-up; 2 of 9 patients who failed ESA treatment were still receiving an ESA. Further research including longer follow-up is warranted to understand how patients with LR-MDS respond to different treatment regimens.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Journal, IO biomarker: Navigating Myelodysplastic and Myelodysplastic/Myeloproliferative Overlap Syndromes. (Pubmed Central) - Nov 24, 2021
Other agents that address red blood cell transfusion dependence in patients with lower-risk MDS and the failure of hypomethylating agents in higher-risk disease are in advanced testing. Finally, a plethora of novel targeted agents and immune checkpoint inhibitors are being evaluated in combination with a hypomethylating agent backbone to augment the depth and duration of response and, we hope, improve overall survival.
- |||||||||| Jakafi oral (ruxolitinib) / Novartis, Incyte, sotatercept (ACE-011) / Acceleron, BMS, Reblozyl (luspatercept-aamt) / Acceleron, BMS
Review, Journal: Improving Ineffective Erythropoiesis in Thalassemia: A Hope on the Horizon. (Pubmed Central) - Nov 12, 2021
Relevant titles and abstracts were screened to choose relevant articles. Further, the full-text articles were retrieved and relevant cross-references were scanned to collect information for the present review.
- |||||||||| Reblozyl (luspatercept-aamt) / BMS, Merck (MSD)
Enrollment open, Trial completion date, Trial primary completion date: Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients (clinicaltrials.gov) - Nov 11, 2021
P1/2, N=50, Recruiting,
Further, the full-text articles were retrieved and relevant cross-references were scanned to collect information for the present review. Not yet recruiting --> Recruiting | Trial completion date: Aug 2028 --> Aug 2029 | Trial primary completion date: Aug 2028 --> Aug 2029
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Journal: Luspatercept in the treatment of lower-risk myelodysplastic syndromes. (Pubmed Central) - Nov 7, 2021
Seminal clinical trials using luspatercept, PACE-MD and MEDALIST, demonstrated impressive efficacy in the treatment of transfusion-dependent anemia in intermediate risk or lower MDS had led to the US FDA approval for this indication. This review summarizes luspatercept mechanisms of action, efficacy/safety data supporting its use and ongoing clinical trials in MDS.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Changes in Quality-of-Life Parameters in Patients Receiving Therapeutic Interventions for Cancer-Associated Anemia: A Systematic Review (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3753;
Therapeutic interventions for CAA included ESAs (n=19; 65.5%), Oral/IV iron (n=1; 3.4%); transfusions (n=2; 6.9%), other agents used in specific conditions (luspatercept (MDS)) n=1; 3.3%, or combinations of these (n=7; 24.1%)...As such, studies may need to utilize more than one HR-QoL tool that gathers information on physical, social and emotional well-being before and after transfusions, while balancing the risk of questionnaire fatigue. A meta-analysis of our systematic review is ongoing and will provide additional information on data gathered thus far.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Serum GDF15 in β-Thalassemia: A Quantitative Marker of Ineffective Erythropoiesis? (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3617;
Median (IQR) levels of GDF15 were significantly different among diagnoses (P<0.0001), and specifically measured 0.22 (0.16-0.34) in H, 0.48 (0.28-0.96) in BTC, 1.35 (0.40-5.46) in NTDT and 5.95 (3.19-10.52) ng/mL in TDT. ( FIG 1A ).
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Luspatercept Redistributes Body Iron to the Liver in Transfusion-Dependent-Thalassemia (TDT) during Erythropoietic Response (GWCC - B401-B402, Level 4) - Nov 5, 2021 - Abstract #ASH2021ASH_2259;
P3
This relocated iron, variably utilized by thalassemic erythron, refluxes back to plasma for hepatocyte and extrahepatic iron uptake, or as heme iron shunts into the liver through hemolytic pathways from intramarrow ineffective erythropoiesis or peripheral breakdown of newly made thalassemic RBC. Macrophage to hepatocyte iron redistribution in TDT appears to be a mechanism of luspatercept.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Tfr2 Genetic Deletion Makes Transfusion-Independent a Murine Model of Transfusion-Dependent β-Thalassemia (GWCC - C202-C204, Level 2) - Nov 5, 2021 - Abstract #ASH2021ASH_2025;
Other recently approved treatments (i.e. Luspatercept and gene therapy) are only partially effective and/or suitable for selected patients...The difference of blood transfusions needs will be evaluated over time for at least 10 additional weeks. Our findings demonstrate that TFR2 targeting represents a new promising therapeutic opportunity for the management of β-thalassemia, worth to be tested both as a monotherapy and in association with available treatments.
- |||||||||| lenalidomide / Generic mfg.
Responses to Sars-Cov-2 Vaccines in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia (GWCC - B308-B309, Level 3) - Nov 5, 2021 - Abstract #ASH2021ASH_1522;
Although the overall sample size was relatively small, most clinical and laboratory variables (including neutropenia and lymphopenia) did not affect the seropositivity rate. Antibody titer levels increased dramatically following the 2 nd vaccine dose, indicating the potential utility for serial vaccination (i.e.
- |||||||||| lenalidomide / Generic mfg.
A Review of Current and Emerging Treatment Options for Myelodysplastic Syndromes (Marriott, Atrium A) - Oct 19, 2021 - Abstract #ASH2021ASH_696;
Throughout the symposium, learners will be able to vote on case scenarios and directly text questions to the panel for their consideration. Discussion topics will include: Risk stratification in MDS Managing anemia in very low–risk, low-risk, or intermediate-risk MDS Novel therapeutic approaches for lower-risk MDS Latest guidance on treating higher-risk MDS and managing relapsed/refractory MDS Future directions on key clinical trials
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Journal: Distinct bone marrow immunophenotypic features define the splicing factor 3B subunit 1 (SF3B1)-mutant myelodysplastic syndromes subtype. (Pubmed Central) - Sep 30, 2021
Splicing factor 3B subunit 1 (SF3B1) mutations define a distinct myelodysplastic syndromes (MDS) patient group with a relatively favourable disease course and high response rates to luspatercept...In addition, we illustrate that SF3B1-mutation type is associated with distinct immunophenotypic features, and show the impact of co-occurrence of a SF3B1 mutation and a deletion of chromosome 5q on bone marrow immunophenotype. These genotype-phenotype associations and phenotypic subtypes within SF3B1-MDS provide leads that may further refine prognostication and therapeutic strategies for this particular MDS subgroup.
- |||||||||| [VIRTUAL] NOVEL APPROACHES IN LOW-RISK MDS () - Sep 26, 2021 - Abstract #MDS2021MDS_292;
Imetelstat, a telomerase inhibitor, is currently in phase 2/3 study in RBC transfusion–dependent and ESA-relapsed or refractory low-risk MDS patients, with encouraging preliminary results. Finally, thrombopoietin-receptor agonists, such as romiplostim or eltrombopag, are not formally approved for patients with MDS but may be a treatment option for thrombocytopenia in patients with blasts <5%.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
[VIRTUAL] THERAPEUTIC TARGETING OF THE TGF BETA PATHWAYS IN MDS () - Sep 26, 2021 - Abstract #MDS2021MDS_291;
In the the talk, we summarize evidence that overactivation of SMAD2/3 signaling pathways in MDSs causes anemia due to impaired erythroid maturation. We will also describe the basis for biological activity of activin receptor ligand traps, novel fusion proteins such as luspatercept that are promising as erythroid maturation agents to alleviate anemia and related comorbidities in MDSs and other conditions characterized by impaired erythroid maturation.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Clinical, Journal: Drug safety in thalassemia: lessons from the present and directions for the future. (Pubmed Central) - Sep 22, 2021
Indeed, although observational studies are the main source of drug safety information in a real-world setting, only eleven studies were identified for iron-chelators and none of these estimated the risk of a given safety outcome but provided only event frequencies. Future work should aim to better leverage existing sources of real-world data, including electronic medical records, administrative healthcare databases and registries to investigate drug safety in thalassemia.
- |||||||||| Review, Journal, PD(L)-1 Biomarker, IO biomarker: Novel therapies emerging in oncology to target the TGF-β pathway. (Pubmed Central) - Sep 17, 2021
The TGF-β ligand traps Bintrafusp alfa (a bifunctional conjugate that binds TGF-β and PD-L1), AVID200 (a computationally designed trap of TGF-β receptor ectodomains fused to an Fc domain) and Luspatercept (a recombinant fusion that links the activin receptor IIb to IgG) offer new ways to fight difficult-to-treat cancers...Minimizing the unintentional inhibition of tumor-suppressing activity and inflammatory effects with the desired restraint on tumor-promoting activities has impeded the clinical development of TGF-β pathway antagonists. A better understanding of the mechanistic details of the TGF-β pathway should lead to more effective TGF-β antagonists and uncover biomarkers that better stratify patient selection, improve patient responses and further the clinical development of TGF-β antagonists.
- |||||||||| Reblozyl (luspatercept-aamt) / BMS, Merck (MSD)
Trial completion date, Trial primary completion date: Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients (clinicaltrials.gov) - Sep 16, 2021
P1/2, N=50, Not yet recruiting,
A better understanding of the mechanistic details of the TGF-β pathway should lead to more effective TGF-β antagonists and uncover biomarkers that better stratify patient selection, improve patient responses and further the clinical development of TGF-β antagonists. Trial completion date: Aug 2025 --> Aug 2028 | Trial primary completion date: Aug 2022 --> Aug 2028
|
