{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:36:42Z","timestamp":1786977402549,"version":"build-2736575974"},"reference-count":28,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004339","name":"Sanofi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004339","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002429","name":"Amgen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Isatuximab (Isa), an anti\u2010CD38 monoclonal antibody, and carfilzomib (K), a next\u2010generation proteasome inhibitor (PI), both have potent single\u2010agent activity in relapsed and refractory multiple myeloma (RRMM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This phase 1b study evaluated the combination of Isa and K in 33 patients with RRMM. Isa was administered by intravenous infusion in 3 dosing cohorts: dose level 1 (Isa at 10 mg\/kg biweekly), dose level 2 (DL2; Isa at 10 mg\/kg weekly for 4 doses and then biweekly), and dose level 3 (Isa at 20 mg\/kg weekly for 4 doses and then biweekly) and all patients received K (20 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      intravenously for cycle 1, days 1 and 2, and then 27 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      for all subsequent doses). A standard 3+3 dose\u2010escalation design was used, no dose\u2010limiting toxicity was observed, and the maximum tolerated dose was not reached. An expansion cohort of 18 patients was enrolled at DL2 to further evaluate safety and efficacy. Responses were assessed with the International Myeloma Working Group response criteria, and patients continued treatment until disease progression or unacceptable toxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>With a median follow\u2010up of 26.7 months, in this heavily pretreated population with a median of 3 prior lines (refractory to PIs and immunomodulatory drugs, 76%; refractory to K, 27%), the overall response rate was 70% (stringent complete response\/complete response, 4; very good partial response, 8; partial response, 11). The median progression\u2010free survival was 10.1 months, and the 2\u2010year survival probability was 76%. The most common treatment\u2010related adverse events (grade 2 or higher) were anemia, leukopenia, neutropenia, thrombocytopenia, hypertension, and infection. Infusion reactions were common (55%) but did not limit dosing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Treatment with Isa plus K was well tolerated with no unexpected toxicity. The combination was effective despite the enrollment of heavily pretreated patients with RRMM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Lay Summary<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>This phase 1b study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of isatuximab and carfilzomib in patients with relapsed and refractory multiple myeloma.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Thirty\u2010three patients were treated: 15 in dose escalation and 18 in dose expansion. Patients received an average of 10 cycles.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The treatment was safe and effective. No unexpected toxicity or drug\u2010drug interactions were noted. Seventy percent of the subjects responded to therapy, and the progression\u2010free survival was 10.1 months.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.33448","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T14:26:45Z","timestamp":1616077605000},"page":"1816-1826","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Phase 1b trial of isatuximab, an anti\u2010CD38 monoclonal antibody, in combination with carfilzomib as treatment of relapsed\/refractory multiple myeloma"],"prefix":"10.1002","volume":"127","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1752-5092","authenticated-orcid":false,"given":"Thomas G.","family":"Martin","sequence":"first","affiliation":[{"name":"Hematology\/Oncology University of California San Francisco Medical Center San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1971-8173","authenticated-orcid":false,"given":"Nina","family":"Shah","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology University of California San Francisco Medical Center San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Richter","sequence":"additional","affiliation":[{"name":"Hematology and Oncology Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David H.","family":"Vesole","sequence":"additional","affiliation":[{"name":"Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy W.","family":"Wong","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology University of California San Francisco Medical Center San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiung\u2010Yu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics University of California San Francisco San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepu","family":"Madduri","sequence":"additional","affiliation":[{"name":"Hematology and Oncology Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2934-6518","authenticated-orcid":false,"given":"Sundar","family":"Jagannath","sequence":"additional","affiliation":[{"name":"Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Siegel","sequence":"additional","affiliation":[{"name":"Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Biran","sequence":"additional","affiliation":[{"name":"Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology University of California San Francisco Medical Center San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"Parekh","sequence":"additional","affiliation":[{"name":"Hematology and Oncology Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hearn J.","family":"Cho","sequence":"additional","affiliation":[{"name":"Tisch Cancer Institute Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela","family":"Munster","sequence":"additional","affiliation":[{"name":"Hematology\/Oncology University of California San Francisco Medical Center San Francisco California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shambavi","family":"Richard","sequence":"additional","affiliation":[{"name":"Hematology and Oncology Icahn School of Medicine at Mount Sinai New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samira","family":"Ziti\u2010Ljajic","sequence":"additional","affiliation":[{"name":"Translational Medicine and Early Development, Pharmacokinetic and Drug Metabolism, Pharmacokinetic Unit, Sanofi Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0405-7480","authenticated-orcid":false,"given":"Ajai","family":"Chari","sequence":"additional","affiliation":[{"name":"Hematology and Oncology Icahn School of Medicine at Mount Sinai New York New 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DimopoulosMA MikhaelJ et al.Isatuximab plus carfilzomib and dexamethasone vscarfilzomib and dexamethasone in relapsed\/refractory multiple myeloma (IKEMA): interim analysis of a phase 3 randomized open\u2010label study [abstract LB2603]. Abstract presented at 25th European Hematology Association Annual Congress; June 11\u201021 2020."},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-1813"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30206-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2017.03.018"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-10-646810"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.138"},{"key":"e_1_2_8_23_1","doi-asserted-by":"crossref","unstructured":"DimopoulosM DytfeldD GropsikiS et al.Elotuzumab plus pomalidomide and dexamethasone for relapsed\/refractory multiple myeloma: efficacy results after additional follow\u2010up of the phase 2 randomized ELOQUENT\u20103 study [abstract PS1370]. Poster presented at: 24th European Hematology Association Annual Congress; June 15 2019; Amsterdam the Netherlands.","DOI":"10.1097\/01.HS9.0000563756.72895.a3"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph10020040"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-0676"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121522"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000722"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.112.047662"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41408-018-0141-0"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cncr.33448","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.33448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T12:28:07Z","timestamp":1760272087000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.33448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":28,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,6]]}},"alternative-id":["10.1002\/cncr.33448"],"URL":"https:\/\/doi.org\/10.1002\/cncr.33448","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,18]]},"assertion":[{"value":"2020-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}