Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F24%3A10487379" target="_blank" >RIV/00064165:_____/24:10487379 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/24:10487379 RIV/00216208:11150/24:10487379 RIV/00179906:_____/24:10487379

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=IM3juD~6jn" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=IM3juD~6jn</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fonc.2024.1398331" target="_blank" >10.3389/fonc.2024.1398331</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa

Popis výsledku v původním jazyce

Background: Luspatercept, an inhibitor of the transforming growth factor beta (TGF-beta) pathway, is a novel treatment for anemic patients with lower-risk myelodysplastic syndromes (MDS) with transfusion dependence (TD) who do not respond to erythropoiesis-stimulating agents (ESA) therapy or are not suitable candidates for this treatment. We present real-world experience with luspatercept therapy from two hematology centers in the Czech Republic. Methods: By January 2024, 54 MDS patients (33 men, 21 women) with a median age of 74 years (range, 55-95) were treated with luspatercept +/- ESA at two Charles University hematology centers in Prague and Hradec Kr &amp; aacute;lov &amp; eacute;. According to the WHO 2016 classification, the cohort included 32 MDS-RS-MLD, seven MDS-MLD, two patients with 5q- + ring sideroblasts (RS), 12 RARS-T, and 1 patient with CMML-0 + RS. SF3B1 mutation data were available for 45 patients. All patients were in the IPSS-R and IPSS-M lower-risk groups (except four IPSS-M high). The median follow-up was 17 months (range, 1-54). All patients were transfusion-dependent. Thirty-five (64.8%) patients had a high transfusion burden (HTB) with &gt;= 4 transfusion units (TU)/8 weeks, and 19 (35.2%) had a low transfusion burden (LTB) (&lt; 4 TU/8 weeks). The median time between diagnosis and initiation of luspatercept was 27 months (range, 4-156). ESA were used prior to luspatercept in 45 patients, and luspatercept was used as first-line treatment in nine patients. Thirty-one (61%) patients were treated simultaneously with ESA. Results: Only patients who received luspatercept for &gt;= 8 weeks (51 patients) were assessed. We evaluated the achievement of transfusion independence (TI) lasting 8, 12, 16, and 24 weeks. Thirty-two (62.7%) patients achieved TI for &gt;= 8 weeks, 31 (60.7%) for &gt;= 12 weeks, 29 (56.8%) for &gt;= 16 weeks, and 25 (49%) for &gt;= 24 weeks. Hematologic improvement (HI) without TI was achieved in six patients (11.7%). Overall, HI + TI was achieved in 38 patients (74.5%). Epoetin alfa was used simultaneously in 31 patients (60.7%). In 21 (55.2%) of all responding patients, concomitant therapy with epoetin alfa led to an improved response, with 16 reaching TI. Thirteen (25.5%) patients were nonresponders. Eight (21%) patients experienced therapy failure and became transfusion-dependent again. Optimal response required a gradual increase in the luspatercept dose to 1.75 mg/kg in up to 35 patients, with 23 responders (TI + HI). Response rates varied by transfusion burden: 79% in LTB and 50% in HTB reached TI. Of RS+ patients, 70% reached TI, while only one out of five RS- patients achieved TI. Among 39 SF3B1-positive patients, 61.6% achieved TI. In the low and very low IPSS-M groups, 86% of patients responded (TI + HI), compared to 62% in the moderate-low group. Luspatercept was well-tolerated, with no adverse events higher than grade II toxicity. Conclusion: We have demonstrated in real-world clinical practice that luspatercept is a very effective agent, even in an unselected, pretreated, significantly TD MDS population. The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients.

Název v anglickém jazyce

Experience with luspatercept therapy in patients with transfusion-dependent low-risk myelodysplastic syndromes in real-world clinical practice: exploring the positive effect of combination with erythropoietin alfa

Popis výsledku anglicky

Background: Luspatercept, an inhibitor of the transforming growth factor beta (TGF-beta) pathway, is a novel treatment for anemic patients with lower-risk myelodysplastic syndromes (MDS) with transfusion dependence (TD) who do not respond to erythropoiesis-stimulating agents (ESA) therapy or are not suitable candidates for this treatment. We present real-world experience with luspatercept therapy from two hematology centers in the Czech Republic. Methods: By January 2024, 54 MDS patients (33 men, 21 women) with a median age of 74 years (range, 55-95) were treated with luspatercept +/- ESA at two Charles University hematology centers in Prague and Hradec Kr &amp; aacute;lov &amp; eacute;. According to the WHO 2016 classification, the cohort included 32 MDS-RS-MLD, seven MDS-MLD, two patients with 5q- + ring sideroblasts (RS), 12 RARS-T, and 1 patient with CMML-0 + RS. SF3B1 mutation data were available for 45 patients. All patients were in the IPSS-R and IPSS-M lower-risk groups (except four IPSS-M high). The median follow-up was 17 months (range, 1-54). All patients were transfusion-dependent. Thirty-five (64.8%) patients had a high transfusion burden (HTB) with &gt;= 4 transfusion units (TU)/8 weeks, and 19 (35.2%) had a low transfusion burden (LTB) (&lt; 4 TU/8 weeks). The median time between diagnosis and initiation of luspatercept was 27 months (range, 4-156). ESA were used prior to luspatercept in 45 patients, and luspatercept was used as first-line treatment in nine patients. Thirty-one (61%) patients were treated simultaneously with ESA. Results: Only patients who received luspatercept for &gt;= 8 weeks (51 patients) were assessed. We evaluated the achievement of transfusion independence (TI) lasting 8, 12, 16, and 24 weeks. Thirty-two (62.7%) patients achieved TI for &gt;= 8 weeks, 31 (60.7%) for &gt;= 12 weeks, 29 (56.8%) for &gt;= 16 weeks, and 25 (49%) for &gt;= 24 weeks. Hematologic improvement (HI) without TI was achieved in six patients (11.7%). Overall, HI + TI was achieved in 38 patients (74.5%). Epoetin alfa was used simultaneously in 31 patients (60.7%). In 21 (55.2%) of all responding patients, concomitant therapy with epoetin alfa led to an improved response, with 16 reaching TI. Thirteen (25.5%) patients were nonresponders. Eight (21%) patients experienced therapy failure and became transfusion-dependent again. Optimal response required a gradual increase in the luspatercept dose to 1.75 mg/kg in up to 35 patients, with 23 responders (TI + HI). Response rates varied by transfusion burden: 79% in LTB and 50% in HTB reached TI. Of RS+ patients, 70% reached TI, while only one out of five RS- patients achieved TI. Among 39 SF3B1-positive patients, 61.6% achieved TI. In the low and very low IPSS-M groups, 86% of patients responded (TI + HI), compared to 62% in the moderate-low group. Luspatercept was well-tolerated, with no adverse events higher than grade II toxicity. Conclusion: We have demonstrated in real-world clinical practice that luspatercept is a very effective agent, even in an unselected, pretreated, significantly TD MDS population. The effect was particularly high in the IPSS-M low and very low groups. We believe that the relatively high response rate in our patients was influenced by the frequent use of a higher dose (1.75 mg/kg) and especially by adding ESA to luspatercept in poorly responding patients.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30205 - Hematology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Oncology

ISSN

2234-943X

e-ISSN

2234-943X

Svazek periodika

14

Číslo periodika v rámci svazku

OCT

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

8

Strana od-do

1398331

Kód UT WoS článku

001334067700001

EID výsledku v databázi Scopus

2-s2.0-85206971372