Luspatercept has been FDA approved for transfusion-dependent beta-thalassemia.
It is a TGF-beta ligand trap that promotes erythroid maturation and reduces transfusion needs.
Sickle Cell Anemia & Related Syndromes
Voxelotor inhibits the polymerization of deoxygenated sickle red blood cells and increases the hemoglobin in SS patients age 12 years or older.
Ropeginterferon alfa-2b was approved by the European Medicines Agency as first-line therapy for patients with polycythemia vera without symptomatic splenomegaly.
A study found that low-dose aspirin (81 mg/day orally) is not as effective as an every 12-hour regimen in reducing the risk of thrombotic complications in low-risk patients.
A novel agent, luspatercept, has been developed to target signaling via the SMAD2–SMAD3 pathway which is constitutively increased in the bone marrow cells of patients with MDS and ineffective erythropoiesis.
In a randomized study, luspatercept induced transfusion independence in 38% of lower-risk MDS patients who did not respond to growth factor therapy compared to 13% in the placebo arm.
Patients with a FLT3 mutation benefit from the addition of the FLT3 kinase inhibitor midostaurin to their regimen.
Patients with secondary AML (evolved from prior myelodysplastic or myeloproliferative disorders) or treatment-associated AML should receive the drug Vyxeos (a liposomal formulation of daunorubicin and cytarabine).
Patients > 75 years of age who are not treated with initial curative intent can derive benefit from newer targeted agents, including the bcl2 inhibitor venetoclax added to a hypomethylating agent or low-dose cyatarabine, enasidenib (targeting IDH2 mutations), ivosidenib (targeting IDH2 mutations), or glasdegib.
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) chemotherapy remains the standard first-line regimen. The substitution of the antibody-drug conjugate brentuximab vedotin for bleomycin (AAVD) has demonstrated superior progression-free survival to ABV but no change in overall survival.
Belantamab mafodotin (an anti-BCMA antibody conjugated to a cytotoxic agent) is as effective as salvage therapy after relapse.
Therapy for AA amyloid is treatment of the underlying cause of inflammation.
Treatment of familial TTR is liver transplantation and of acquired TTR is tafamidis or inotersen.