{ "abstract": "Background: With the growing use of anti-CD38 therapies in early multiple myeloma (MM) management, there is a need for data in patients previously exposed to anti-CD38 therapy to guide decision making. In the Phase 3 IRAKLIA trial (NCT05405166), patients with relapsed/refractory MM (RRMM) received the anti-CD38 monoclonal antibody isatuximab (Isa) subcutaneously (SC) delivered via an innovative on-body injector (OBI) or intravenously (IV), with pomalidomide and dexamethasone (Pd). In this post hoc analysis, we examined outcomes in IRAKLIA patients with vs without prior anti-CD38 exposure. Methods: RRMM patients ≥18 years with ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor were randomized to receive Isa SC (n=263) or IV (n=268) weekly in Cycle 1, then every 2 weeks, with Pd. Patients with prior anti-CD38 exposure <9 months (mos) before randomization or intolerance to anti-CD38 were excluded. Refractory patients were defined as those who failed to achieve minimal response on treatment or had progression within 60 days after last dose. Patients receiving Isa SC or IV were pooled. Results: Overall, 67 patients (12.6%) had prior anti-CD38 exposure with a median washout period of 20.2 mos, of which 26 (38.8%) were anti-CD38 refractory. Baseline characteristics were largely consistent between patients with or without prior anti-CD38 exposure; the median follow-up for the overall population was 12 mos. Patients with prior anti-CD38 exposure had an overall response rate (ORR) of 52.2%, 12-mo progression-free survival (PFS) rate of 40.6%, and median PFS of 8.5 mos. In patients without prior exposure, an ORR of 73.5%, 12-mo PFS of 68.8%, and non-estimable (NE) median PFS were reported. Anti-CD38 non-refractory vs refractory patients had an ORR of 48.8% vs 57.7%, 12-mo PFS of 38.9% vs 42.2%, and median PFS of 9.0 vs 7.5 mos. Patients with a longer washout period (>median of 20.2 mos) had an ORR of 63.6%, 12-mo PFS of 61.8% and NE median PFS, whereas patients whose prior anti-CD38 therapy ended more recently (≤median of 20.2 mos) had an ORR of 41.2%, 12-mo PFS of 19.2%, and median PFS of 6.7 mos. The safety profile of Isa + Pd was similar in patients with vs without prior anti-CD38 exposure. Conclusions: Isa + Pd demonstrated clinical benefit across anti-CD38–naïve, anti-CD38–exposed, and anti-CD38–refractory patients. A washout period >median of 20.2 mos resulted in outcomes comparable to those in anti-CD38–naïve patients, and outcomes were consistent between anti-CD38–exposed and anti-CD38–refractory patients after a > 9-mo washout period. Efficacy of Isa + Pd in patients with prior anti-CD38 exposure from the IRAKLIA trial presents an opportunity to address an unmet need in a difficult-to-treat patient population.", "abstract_shown": true, "affiliations": [ "Institut Català d'Oncologia and Josep Carreras Research Institute, Hospital Germans Trias Pujol (IJC-IGTP-ICO), Barcelona, Catalonia, Spain", "University of Lublin (KUL), Lublin, Lublin Voivodeship, Poland", "Instituto Oncológico Fundación Arturo López Pérez (FALP), Santiago, Santiago Metropolitan Region, Chile", "Department of Haematology, Shengjing Hospital of China Medical University (SJH), Shenyang, Liaoning, China", "Department of Haematology, Calvary Mater Newcastle, Waratah, New South Wales, Australia", "Department of Haematology, The Royal Adelaide Hospital, SA Health (RAH), Adelaide, South Australia, Australia", "South Pest Central Hospital, National Institute for Hematology and Infectious Diseases (NIHID), Budapest, Hungary; Semmelweis University (SE), Department of Internal Medicine and Hematology, Budapest, Hungary", "Plasma Cell Dyscrasias Center, Department of Hematology, Jagiellonian University Medical College (JUMC), Kraków, Lesser Poland, Poland", "Inmunocel, Santiago, Santiago Metropolitan Region, Chile", "Peking University (PKU), Beijing, China", "Oslo Myeloma Center, Department of Hematology, Oslo University Hospital (OUH), Norway", "Sydney Adventist Hospital (SAH), Wahroonga, New South Wales, Australia", "Monash University (MON), Melbourne, Victoria, Australia", "Division of Hematology/Oncology, Mayo Clinic, Jacksonville, Florida, United States", "Spartanburg Medical Center (SMC), Center for Hematology/Oncology, Spartanburg, South Carolina, United States", "Sanofi, Cambridge, Massachusetts, United States", "Sanofi R&D, Vitry-sur-Seine, Île-de-France, France", "Sanofi, Morristown, New Jersey, United States", "Department of Hematology and Oncology, Clínica São Germano, São Paulo, SP, Brasil", "1st Department of Medicine – Department of Hematology, First Faculty of Medicine Charles University and General Hospital, Prague, Czech Republic" ], "article_type": null, "arxiv": null, "author_total": 20, "authors": [ { "affs": [ 0 ], "name": "Albert ORIOL" }, { "affs": [ 1 ], "name": "Marek HUS" }, { "affs": [ 2 ], "name": "Raimundo GAZITUA" }, { "affs": [ 3 ], "name": "Aijun LIAO" }, { "affs": [ 4 ], "name": "Wojt JANOWSKI" }, { "affs": [ 5 ], "name": "Cindy Huey-shin LEE" }, { "affs": [ 6 ], "name": "Gabor MIKALA" }, { "affs": [ 7 ], "name": "Artur JURCZYSZYN" }, { "affs": [ 8 ], "name": "Alejandro BERKOVITS" }, { "affs": [ 9 ], "name": "Jin LU" }, { "affs": [ 10 ], "name": "Fredrik SCHJESVOLD" }, { "affs": [ 11 ], "name": "Silvia LING" }, { "affs": [ 12 ], "name": "Andrew SPENCER" }, { "affs": [ 13 ], "name": "Sikander AILAWADHI" }, { "affs": [ 14 ], "name": "Tondre T. BUCK" }, { "affs": [ 15 ], "name": "Umer KHAN" }, { "affs": [ 16 ], "name": "Florence SUZAN" }, { "affs": [ 17 ], "name": "Maya Stefanova- URENA" }, { "affs": [ 18 ], "name": "Vania HUNGRIA" }, { "affs": [ 19 ], "name": "Ivan ŠPIčKA" } ], "bibtex": "https://research.draconitic.com/paper/awgnrmtcy2hss.bib", "cited_by": 0, "doi": "10.1016/j.htct.2026.107882", "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926016299", "id": "awgnrmtcy2hss", "issns": [ "2531-1379", "2531-1387" ], "landing_url": "https://doi.org/10.1016/j.htct.2026.107882", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RC633-647.5" ], [ "openalex", "2720|Multiple Myeloma Research and Treatments" ] ], "openalex": "W7223113986", "pdf_url": "https://www.sciencedirect.com/science/article/pii/S2531137926016299/pdf", "pmcid": null, "pmid": null, "published": "2026-10-23", "publisher": "Elsevier", "ris": "https://research.draconitic.com/paper/awgnrmtcy2hss.ris", "sources": [ { "first_seen": "2026-10-30T13:43:26Z", "native_id": "6524021f69f844c09b6b7f5e059e1f84", "source": "doaj", "url": "https://doi.org/10.1016/j.htct.2026.107882" } ], "subjects": [ { "field": "medicine", "origin": "lcc:RC633-647.5", "subfield": "endocrinology-metabolism" } ], "title": "ISATUXIMAB PLUS POMALIDOMIDE-DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS BY PRIOR ANTI-CD38 EXPOSURE FROM THE PHASE 3 IRAKLIA TRIAL", "title_text": "ISATUXIMAB PLUS POMALIDOMIDE-DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: SUBGROUP ANALYSIS BY PRIOR ANTI-CD38 EXPOSURE FROM THE PHASE 3 IRAKLIA TRIAL", "type": "peer-reviewed", "updated_at": "2026-10-30T13:43:26Z", "url": "https://research.draconitic.com/paper/awgnrmtcy2hss", "venue": "Hematology, Transfusion and Cell Therapy", "versions": [] }