New Tefferi paper text (3)

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cheng_ho
Posts: 202
Joined: Sun Apr 03, 2016 11:27 pm

New Tefferi paper text (3)

Post by cheng_ho » Mon Apr 19, 2021 5:09 pm

with MDS-RS, three (38%) of eight transfusion-dependent patients became transfusion-independent at a median time of 11 weeks and their response lasted for a median of 28 weeks (range, 9–37); one of the three patients also had resolution of leukocytosis and thrombocytosis. From mutation standpoint, 3 patients were mutated for JAK2, seven for SF3B1 and one for U2AF1. All three anemia responders and the fourth patient with spleen response were SF3B1 mutated. Treatment-emergent side effects included severe myelosuppression and liver function test abnormalities. In a more recent study of imetelestat therapy in 57 patients with transfusion-dependent lower-risk MDS that was refractory to ESAs,12 the 8- and 24-week transfusion independence rates were 37% and 23%, respectively, with a median response duration of 65 weeks. Furthermore, CR was reported in 5 (9%) patients and marrow CR (mCR) in 6 (11%); 5 of the 11 mCR/CR patients had complete resolution of dysplasia; 8 of the 11 CR/mCR patients demonstrated RS on screening BM aspirate and 4 had complete disappearance of BM RS, Among 13 patients with pre- and post-treatment mutation analysis, 11 patients had baseline SF3B1 mutations, and 10 had a reduction (range, 10% to 93%) in SF3B1 variant allele frequency from baseline. Imetelestat has also shown activity in essential thrombocythemia13 and its potential disease-modifying activity in myelofibrosis was further suggested in an ongoing study.14 Taken together, the aforementioned data suggested a broader disease-modifying activity for imetelestat in myeloid neoplasms, with or without RS, and possibly influenced by the presence or absence of specific mutations. Accordingly, imetelestat might be preferable to luspatercept if the goal of therapy were to prolong survival or effect suppression of the malignant clone. However, such a prospect requires validation in a controlled study, whose likelihood of success might depend on selection of study patients based on specific molecular markers.7,8,12 Such an approach might also identify those patients who are unlikely to respond to treatment, and thus spare them from being uneccesarily exposed to drug side effects. In contrast to what might be the case with imetelestat, the therapeutic activity of luspatercept appears to be limited to partial amelioration of anemia, in a subset of patients with RS; furthermore, despite its interesting (assumed) mechanism of action, the overall impact of luspatercept on producing robust and durable anemia responses currently remains less than impressive. Previously published work have documented the value of both ESAs 15 and lenalidomide ,16-20 for the treatment of anemia associated with MDS/MPN-RS-T; similar response rates to both ESAs and

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