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Phase Ib study of eltrombopag and azacitidine in patients with high‐risk myelodysplastic syndromes and related disorders (the ELASTIC study)
Summary Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of
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| Published in: | British journal of haematology 2022-10, Vol.199 (2), p.222-229 |
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| Main Authors: | , , , , , , , , , , , , |
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| container_end_page | 229 |
| container_issue | 2 |
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| container_title | British journal of haematology |
| container_volume | 199 |
| creator | Sternberg, Alexander Boucher, Rebecca Coulthard, Helen Chantal Raghavan, Manoj Culligan, Dominic Jackson, Aimee Cargo, Catherine Dennis, Mike Metzner, Marlen O'Sullivan, Jennifer Moore, Rachel Bowen, David Vyas, Paresh |
| description | Summary
Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of |
| doi_str_mv | 10.1111/bjh.18389 |
| format | article |
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Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 109/l received eltrombopag ranging from 25 to 300 mg. An 8‐day pre‐phase of eltrombopag was followed by two cycles of combined therapy. Amongst 31 patients, there were no dose‐limiting toxicities. The maximum tolerated dose (MTD) was 300 mg. Transient increases in bone marrow blasts at day 8 were common but no patient had protocol‐defined progression following eltrombopag monotherapy. Marrow response rates after three and six treatment cycles were 32% and 29% respectively. In all, 70% of patients treated below and 36% treated at the MTD achieved a modified International Working Group 2006 platelet response at the end of cycle two. Of the platelet transfusion independent patients at baseline, 67% treated at the MTD became transfusion dependent during the first two cycles of treatment. Apart from lack of disease progression, our findings concur with a previously reported Phase III study (A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine [SUPPORT]). We conclude that eltrombopag/azacitidine is safe in terms of conventional measures defined by adverse‐event reporting. However, in light of SUPPORT and our own descriptive findings regarding efficacy, further combination studies in high‐risk disease should be considered with caution.</description><identifier>ISSN: 0007-1048</identifier><identifier>EISSN: 1365-2141</identifier><identifier>DOI: 10.1111/bjh.18389</identifier><identifier>PMID: 35918828</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>azacitidine ; Azacitidine - therapeutic use ; Benzoates - therapeutic use ; Bone marrow ; Drug Combinations ; eltrombopag ; Hematology ; Humans ; Hydrazines - therapeutic use ; Myelodysplastic syndrome ; myelodysplastic syndromes (MDS) ; Myelodysplastic Syndromes - drug therapy ; Patients ; Platelets ; Pyrazoles - therapeutic use ; Thrombocytopenia ; Treatment Outcome</subject><ispartof>British journal of haematology, 2022-10, Vol.199 (2), p.222-229</ispartof><rights>2022 British Society for Haematology and John Wiley & Sons Ltd.</rights><rights>2022 British Society for Haematology and John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3889-890a9065be8dbbf3b6c8e70294a6d216951a8575b52289e346df614f524c44f43</citedby><cites>FETCH-LOGICAL-c3889-890a9065be8dbbf3b6c8e70294a6d216951a8575b52289e346df614f524c44f43</cites><orcidid>0000-0003-1047-0826</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35918828$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sternberg, Alexander</creatorcontrib><creatorcontrib>Boucher, Rebecca</creatorcontrib><creatorcontrib>Coulthard, Helen Chantal</creatorcontrib><creatorcontrib>Raghavan, Manoj</creatorcontrib><creatorcontrib>Culligan, Dominic</creatorcontrib><creatorcontrib>Jackson, Aimee</creatorcontrib><creatorcontrib>Cargo, Catherine</creatorcontrib><creatorcontrib>Dennis, Mike</creatorcontrib><creatorcontrib>Metzner, Marlen</creatorcontrib><creatorcontrib>O'Sullivan, Jennifer</creatorcontrib><creatorcontrib>Moore, Rachel</creatorcontrib><creatorcontrib>Bowen, David</creatorcontrib><creatorcontrib>Vyas, Paresh</creatorcontrib><title>Phase Ib study of eltrombopag and azacitidine in patients with high‐risk myelodysplastic syndromes and related disorders (the ELASTIC study)</title><title>British journal of haematology</title><addtitle>Br J Haematol</addtitle><description>Summary
Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 109/l received eltrombopag ranging from 25 to 300 mg. An 8‐day pre‐phase of eltrombopag was followed by two cycles of combined therapy. Amongst 31 patients, there were no dose‐limiting toxicities. The maximum tolerated dose (MTD) was 300 mg. Transient increases in bone marrow blasts at day 8 were common but no patient had protocol‐defined progression following eltrombopag monotherapy. Marrow response rates after three and six treatment cycles were 32% and 29% respectively. In all, 70% of patients treated below and 36% treated at the MTD achieved a modified International Working Group 2006 platelet response at the end of cycle two. Of the platelet transfusion independent patients at baseline, 67% treated at the MTD became transfusion dependent during the first two cycles of treatment. Apart from lack of disease progression, our findings concur with a previously reported Phase III study (A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine [SUPPORT]). We conclude that eltrombopag/azacitidine is safe in terms of conventional measures defined by adverse‐event reporting. However, in light of SUPPORT and our own descriptive findings regarding efficacy, further combination studies in high‐risk disease should be considered with caution.</description><subject>azacitidine</subject><subject>Azacitidine - therapeutic use</subject><subject>Benzoates - therapeutic use</subject><subject>Bone marrow</subject><subject>Drug Combinations</subject><subject>eltrombopag</subject><subject>Hematology</subject><subject>Humans</subject><subject>Hydrazines - therapeutic use</subject><subject>Myelodysplastic syndrome</subject><subject>myelodysplastic syndromes (MDS)</subject><subject>Myelodysplastic Syndromes - drug therapy</subject><subject>Patients</subject><subject>Platelets</subject><subject>Pyrazoles - therapeutic use</subject><subject>Thrombocytopenia</subject><subject>Treatment Outcome</subject><issn>0007-1048</issn><issn>1365-2141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNp1kM1O20AURkdVEYSfRV-gGqmbZmGYX2e8hIg2qSKBRFhbM55rPKljuzMTIXfVJ0B9Rp4EN4buuJu7OTqfdBD6RMk5He7CbKpzqrjKPqAJ5alMGBX0I5oQQmYJJUIdoeMQNoRQTiQ9REdcZlQppibo6bbSAfDS4BB3tsdtiaGOvt2attMPWDcW69-6cNFZ1wB2De50dNDEgB9drHDlHqrnP3-9Cz_xtoe6tX3oah2iK3DoGzuYIOw1HmodwWLrQust-IC_xgrw9erybr2cj_PTU3RQ6jrA2es_QfffrtfzRbK6-b6cX66SgiuVJSojOiOpNKCsMSU3aaFgRlgmdGoZTTNJtZIzaSRjKgMuUlumVJSSiUKIUvAT9GX0dr79tYMQ8027880wmbMZo5JTSdRATUeq8G0IHsq8826rfZ9Tkv8rnw_l8335gf38atyZLdj_5FvqAbgYgUdXQ_--Kb_6sRiVL5jhjuQ</recordid><startdate>202210</startdate><enddate>202210</enddate><creator>Sternberg, Alexander</creator><creator>Boucher, Rebecca</creator><creator>Coulthard, Helen Chantal</creator><creator>Raghavan, Manoj</creator><creator>Culligan, Dominic</creator><creator>Jackson, Aimee</creator><creator>Cargo, Catherine</creator><creator>Dennis, Mike</creator><creator>Metzner, Marlen</creator><creator>O'Sullivan, Jennifer</creator><creator>Moore, Rachel</creator><creator>Bowen, David</creator><creator>Vyas, Paresh</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>H94</scope><orcidid>https://orcid.org/0000-0003-1047-0826</orcidid></search><sort><creationdate>202210</creationdate><title>Phase Ib study of eltrombopag and azacitidine in patients with high‐risk myelodysplastic syndromes and related disorders (the ELASTIC study)</title><author>Sternberg, Alexander ; Boucher, Rebecca ; Coulthard, Helen Chantal ; Raghavan, Manoj ; Culligan, Dominic ; Jackson, Aimee ; Cargo, Catherine ; Dennis, Mike ; Metzner, Marlen ; O'Sullivan, Jennifer ; Moore, Rachel ; Bowen, David ; Vyas, Paresh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3889-890a9065be8dbbf3b6c8e70294a6d216951a8575b52289e346df614f524c44f43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>azacitidine</topic><topic>Azacitidine - therapeutic use</topic><topic>Benzoates - therapeutic use</topic><topic>Bone marrow</topic><topic>Drug Combinations</topic><topic>eltrombopag</topic><topic>Hematology</topic><topic>Humans</topic><topic>Hydrazines - therapeutic use</topic><topic>Myelodysplastic syndrome</topic><topic>myelodysplastic syndromes (MDS)</topic><topic>Myelodysplastic Syndromes - drug therapy</topic><topic>Patients</topic><topic>Platelets</topic><topic>Pyrazoles - therapeutic use</topic><topic>Thrombocytopenia</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sternberg, Alexander</creatorcontrib><creatorcontrib>Boucher, Rebecca</creatorcontrib><creatorcontrib>Coulthard, Helen Chantal</creatorcontrib><creatorcontrib>Raghavan, Manoj</creatorcontrib><creatorcontrib>Culligan, Dominic</creatorcontrib><creatorcontrib>Jackson, Aimee</creatorcontrib><creatorcontrib>Cargo, Catherine</creatorcontrib><creatorcontrib>Dennis, Mike</creatorcontrib><creatorcontrib>Metzner, Marlen</creatorcontrib><creatorcontrib>O'Sullivan, Jennifer</creatorcontrib><creatorcontrib>Moore, Rachel</creatorcontrib><creatorcontrib>Bowen, David</creatorcontrib><creatorcontrib>Vyas, Paresh</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>British journal of haematology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sternberg, Alexander</au><au>Boucher, Rebecca</au><au>Coulthard, Helen Chantal</au><au>Raghavan, Manoj</au><au>Culligan, Dominic</au><au>Jackson, Aimee</au><au>Cargo, Catherine</au><au>Dennis, Mike</au><au>Metzner, Marlen</au><au>O'Sullivan, Jennifer</au><au>Moore, Rachel</au><au>Bowen, David</au><au>Vyas, Paresh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phase Ib study of eltrombopag and azacitidine in patients with high‐risk myelodysplastic syndromes and related disorders (the ELASTIC study)</atitle><jtitle>British journal of haematology</jtitle><addtitle>Br J Haematol</addtitle><date>2022-10</date><risdate>2022</risdate><volume>199</volume><issue>2</issue><spage>222</spage><epage>229</epage><pages>222-229</pages><issn>0007-1048</issn><eissn>1365-2141</eissn><abstract>Summary
Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 109/l received eltrombopag ranging from 25 to 300 mg. An 8‐day pre‐phase of eltrombopag was followed by two cycles of combined therapy. Amongst 31 patients, there were no dose‐limiting toxicities. The maximum tolerated dose (MTD) was 300 mg. Transient increases in bone marrow blasts at day 8 were common but no patient had protocol‐defined progression following eltrombopag monotherapy. Marrow response rates after three and six treatment cycles were 32% and 29% respectively. In all, 70% of patients treated below and 36% treated at the MTD achieved a modified International Working Group 2006 platelet response at the end of cycle two. Of the platelet transfusion independent patients at baseline, 67% treated at the MTD became transfusion dependent during the first two cycles of treatment. Apart from lack of disease progression, our findings concur with a previously reported Phase III study (A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine [SUPPORT]). We conclude that eltrombopag/azacitidine is safe in terms of conventional measures defined by adverse‐event reporting. However, in light of SUPPORT and our own descriptive findings regarding efficacy, further combination studies in high‐risk disease should be considered with caution.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>35918828</pmid><doi>10.1111/bjh.18389</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-1047-0826</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | British journal of haematology, 2022-10, Vol.199 (2), p.222-229 |
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| source | Wiley |
| subjects | azacitidine Azacitidine - therapeutic use Benzoates - therapeutic use Bone marrow Drug Combinations eltrombopag Hematology Humans Hydrazines - therapeutic use Myelodysplastic syndrome myelodysplastic syndromes (MDS) Myelodysplastic Syndromes - drug therapy Patients Platelets Pyrazoles - therapeutic use Thrombocytopenia Treatment Outcome |
| title | Phase Ib study of eltrombopag and azacitidine in patients with high‐risk myelodysplastic syndromes and related disorders (the ELASTIC study) |
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