Mateos, Maria-VictoriaRodriguez Otero, PaulaKoh, YoungilMartinez-Lopez, JoaquinParmar, GurdeepPrince, H. MilesQuach, HangRibas, PazHermansen, EmilHungria, Vania T. M.Kalayoğlu Beşışık, SevgiKim, Jin SeokLeleu, XavierPeceliunas, ValdasSchjesvold, FredrikSevindik, Ömür GökmenLavrova, TatianaDubin, FranckDevisme, ChristineLepine, LucieGhobrial, Irene2023-03-172023-03-172022Mateos, M.-V., Rodriguez Otero, P., Koh, Y., Martinez-Lopez, J., Parmar, G., Prince, H. M. ... Ghobrial, I. (2022). Isatuximab in combination with lenalidomide and dexamethasone in patients with high-risk smoldering multiple myeloma: Updated safety run-in results from the randomized phase 3 ithaca study. American Society of Hematology içinde (7317-7319. ss.). https://dx.doi.org/10.1182/blood-2022-1573020006-49711528-0020https://dx.doi.org/10.1182/blood-2022-157302https://hdl.handle.net/20.500.12511/10630Background: Results from a randomized, Phase 3 study by the Spanish Myeloma Group (PETHEMA/GEM) previously showed that treatment with lenalidomide plus dexamethasone (Rd) may delay progression to active disease in patients (pts) with high-risk smoldering multiple myeloma (SMM), compared with observation. To further improve outcomes, addition of the anti-CD38 antibody isatuximab (Isa) to lenalidomide and dexamethasone (Isa-Rd) for the treatment of pts with high-risk SMM is being evaluated in the ongoing, randomized, multi-center, Phase 3 ITHACA study (NCT04270409). Initial findings from the safety run-in analysis of this trial have shown a manageable safety profile and encouraging, preliminary anti-myeloma activity. We now report updated safety and efficacy results from the safety run-in part of ITHACA at a median follow-up of 19.4 months. Methods: Pts were included in the study if they had been diagnosed within 5 years with SMM (per the International Myeloma Working Group [IMWG] criteria) and had high-risk SMM according to the Mayo '20-2-20' and/or updated PETHEMA model criteria. Pts who had received prior anti-myeloma treatment were not eligible. Enrolled pts received Isa 10 mg/kg IV on day (D) 1, 8, 15, and 22 in cycle (C) 1, D1 and D15 C2-12, D1 C13-36; plus R D1-21 (25 mg C1-9; 10 mg C10-24) and d weekly (40 mg, 20 mg for ?75 yr-old pts C1-9; 20 mg C10-24). Cycle duration was 28 days. Safety evaluations included treatment-emergent AEs (TEAEs)/serious AEs and laboratory parameters, graded by NCI-CTCAE v5.0. Response was determined by IMWG criteria (2016). Mandatory imaging by MRI and/or low-dose whole-body CT/PET-CT, and assessments of minimal residual disease (MRD, by next-generation sequencing in pts with very good partial response [VGPR] or better), were performed at protocol-defined time points. The primary study objective for the safety run-in was to confirm the recommended dose of Isa in combination with Rd. Overall response rate (ORR) and MRD negativity rate at 10-5 sensitivity were included as secondary endpoints.eninfo:eu-repo/semantics/openAccess3 Ithaca StudyHigh-Risk Smoldering Multiple MyelomaDexamethasoneLenalidomideConference Object140Supplement: 17317731910.1182/blood-2022-157302Q1000893230300143