New Tefferi paper text (2)

Forum rules
- Comments must be civil and on topic
- Back up claims with evidence/reasoning/sources (posting links is allowed)
- No commercials/harassment/spam
Post Reply
cheng_ho
Posts: 202
Joined: Sun Apr 03, 2016 11:27 pm

New Tefferi paper text (2)

Post by cheng_ho » Mon Apr 19, 2021 5:08 pm

In a phase-3, placebo-controlled MEDALIST trial (n=229) of transfusion-dependent patients with low/intermediate risk MDS-RS and who failed treatment with erythropoiesis stimulating agents (ESAs) or serum erythropoietin (Epo) level of >200U/L, 28% of patients in the luspatercept treated group vs 8% in the placebo group achieved transfusion-independence for a consecutive 12 weeks period during weeks 1 through 24; median duration of transfusion independence was 31 vs 14 weeks, respectively; SF3B1 mutant allele burden was not affected by treatment and did not influence treatment response.9 Luspatercept-treated patients also experienced higher rates of erythroid-lineage hematologic improvement (53% vs 12%) and platelet response (63% vs 33%) while the rate of leukemic progression was similar between the two treatment arms. Relatively frequent adverse events included headaches, dizziness, fatigue, nausea, diarrhea, bone pain and abdominal pain. The activity of luspatercept has also been examined in MDS/MPN-RS-T10 and myelofibrosis.11 In the former, study patients (n=23) were retrospectively identified from the aforementioned MEDALIST trial of whom 14 received luspatercept and 9 placebo; 9 (64%) vs 2 (22.2%) patients, respectively, were reported to have achieved 8-week duration of transfusion independence in the first 24 weeks. In a separate phase-2 study of 79 pts with myelofibrosis-associated anemia, 43 were identified as being transfusion dependent; achievement of transfusion-independence for 12 consecutive weeks, during the first 24 weeks of treatment, was observed in only 2 (10%) patients receiving luspatercept alone and in 6 (27%) patients receiving luspatercept in combination with ruxolitinib.11 Telomerase is a holoenzyme made up of human telomerase reverse transcriptase, an RNA template and specialized proteins, and participates in the synthesis and maintenance of telomere length in rapidly dividing cells. Imetelstat is a lipid-conjugated oligonucleotide that targets the RNA template of human telomerase. In 2015, Mayo Clinic investigators reported on 33 patients with high/intermediate-2-risk myelofibrosis who were treated with imetelstat (2-hour intravenous infusion; starting dose, 9.4 mg/kg every 1 to 3 weeks) and observed a complete (n=4; 12%) or partial remission in 7 patients (21%).7 All 4 patients with complete remission (CR) experienced reversal of bone marrow fibrosis while 3 of the 4 achieved molecular response as well. Interestingly, the CR rate was 38% among patients with spliceosome mutations (SF3B1 or U2AF1) versus 4% among those without such mutations. The particular observation suggested potential activity in myeloid neoplasms with similar mutations, including MDS-RS and MDS/MPN-RS-T.8 In a separate study of 9 such patients by the same investigators, including 5 with MDS/MPN-RS-T and 3

Post Reply