isatuximab subcutaneous (SAR650984 SC) / Sanofi - LARVOL DELTA

A lean thinking approach to improve efficiency in providing immune-chemotherapy injection in out-patient service: A pivotal study (ASH 2025) - "Thus, room A can be dedicated to longer infusion times (> 2 hours, like CHOP, ABVD, obinotuzumab etc), B room for intermediate therapies (30 min-2 hours, like carfilzomib, decitabine), room D for short therapies (less than 10 minutes, like bispecific antibodies, daratumumab, bortezomib), room C for device maintenance and blood drawing, obtaining a further NVT reduction to 57 minutes but a NVTp worsening to 48%...Based on these scenarios, we developed an integrated software solution with AI functionality based on the automation of infusion station assignment, eliminating the distinction by pathology and length of treatment, reducing the average patient waiting time to 13 minutes, the in-patient stay to 23 minutes for short-term therapies, such as daratumumab and bispecifics, and 45 minutes for intermediate therapies such as isatuximab infusion. Conclusions Our approach proposes leveraging existing infrastructure resources, particularly infusion chairs, which are often..."

Clinical • Hematological Malignancies • Oncology

Isatuximab subcutaneous in relapsed/refractory multiple myeloma: Exposure-response and serum m-protein dynamics analyses from phase 3 iraklia Study and the phase 1b Study (ASH 2025) - P1, P3 | "Introduction: The first Phase (Ph) 3 study in multiple myeloma (MM) using an on-body injector (OBI),IRAKLIA (NCT05405166), is a randomized, global, open-label, non-inferiority (NI) study investigatingisatuximab (Isa) subcutaneous (SC) vs intravenous (IV) +pomalidomide and dexamethasone (Pd) inrelapsed/refractory MM (RRMM). E-R analyses confirmed CT4W as the best efficacy predictor, and higher Isa exposure wasassociated with higher ORR for IsaSC and IV +Pd. Q1 pts had more aggressive MM characteristics,reducing tx response and increasing AE development risk; with BL MM characteristics and high dosemodification rates (mainly to manage AEs) likely confounding Q1 of the E-R curve. The completion of 4weekly doses before switching to Q2W regimen would benefit pts receiving Isa."

P1 data • P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Plasmacytoma • Pneumonia • Respiratory Diseases • Thrombocytopenia

Isatuximab (Isa) subcutaneous (SC) via an on-body injector (OBI) vs isa intravenous (IV), plus pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma (RRMM): East asia subgroup results from the randomized, non-inferiority, phase 3 iraklia study (ASH 2025) - P3 | "Baseline characteristics of the East Asian subgroup were generallybalanced between the two arms and generally comparable to the overall global population (median age62 years; median 2 prior LOT; 29.5% high-risk cytogenetics; 82.9% refractory to lenalidomide; 7.6% priorexposure to daratumumab). The efficacy, safety and pharmacokinetic results between Isa SC vs IV + Pd in the East Asianpopulation from the IRAKLIA study were consistent with the results of the overall global population, inwhich non-inferiority of ORR, Ctrough at C6D1, ≥VGPR and Ctrough at C2D1 was demonstrated andstatistically significantly fewer infusion reactions and higher patient satisfaction were also noted for SC vsIV. These results support the potential use of Isa SC delivered via OBI in East Asian patients anddemonstrate the potential of this delivery method to improve patient experience and practice efficiency."

Clinical • Head-to-Head • P3 data • Hematological Malignancies • Multiple Myeloma

Isatuximab subcutaneous by on-body injector in Relapsed/Refractory multiple myeloma in the Phase 3 iraklia study: Effect of body weight on pharmacokinetics and clinical outcome (ASH 2025) - P3 | "Introduction: IRAKLIA is an international, open-label, non-inferiority (NI) trial (NCT05405166) investigatingisatuximab (Isa) subcutaneous (SC) vs intravenous (IV) administration, plus pomalidomide-dexamethasone (Pd) and the first Phase 3 multiple myeloma (MM) trial using an on-body injector (OBI).IRAKLIA demonstrated NI in its co-primary endpoints: overall response rate (ORR) and steady statetrough concentration (Ctrough; Cycle(C) 6 Day(D) 1 predose). No notable impact from IsaOBI flat dosing was observed across BW groups. Flat-dose IsaOBI showed consistent safety and efficacy across different BW groups, with differences likely linked to BLdisease characteristics according to the E-R analysis. The IsaOBI C2D1 Ctrough, a time-independentpredictor of efficacy, was similar to, or higher vs IsaIV in each BW group, supportive of a flat doseproviding adequate exposure without need for adjustment."

Clinical • Clinical data • P3 data • PK/PD data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Plasmacytoma • B2M

Home administration of isatuximab subcutaneous by on-body injector in Relapsed/Refractory multiple myeloma in the Phase 3 iraklia study (ASH 2025) - P2, P3 | "Introduction: IRAKLIA (NCT05405166) is an ongoing, global, non-inferiority trial of isatuximab (Isa)subcutaneous (SC) administration plus pomalidomide-dexamethasone (Pd), and the first Phase 3 multiplemyeloma (MM) trial using an on-body injector (OBI) for SC administration. Initial data from the ongoing IRAKLIA trial support the safety of at-home administration ofIsa SC OBI for the treatment of patients with MM. Home administration was well tolerated, with no safetyconcerns and a median injection time of 13 minutes consistent with in-clinic use of Isa SC OBI. The optionof either home or outpatient administration of Isa SC OBI for patients with MM allows for greaterflexibility and accessibility of treatment, with the potential to improve patient care and reduce commonbarriers to patient retention and therapy compliance."

P3 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma

Single-cell immune landscape associated with isatuximab, carfilzomib, lenalidomide, and dexamethasone induction efficacy in newly diagnosed myeloma (ASH 2025) - "Introduction:Quadruplet regimens combining CD38-targeting monoclonal antibodies, such as Isatuximab orDaratumumab, with proteasome inhibitors, immunomodulatory drugs (IMiDs), and dexamethasone haverecently emerged as the standard-of-care induction therapy for newly diagnosed multiple myeloma(NDMM). Our study provides a comprehensive single-cell atlas of the immune microenvironment in NDMMpatients before and after IsaKRD induction. We reveal coordinated reshaping of both lymphoid andmyeloid compartments, with immune signatures that correlate with MRD status and treatment efficacy.These findings underscore the importance of immune remodeling in shaping therapeutic outcomes andoffer potential avenues for biomarker development and immune-based interventions in multiplemyeloma."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma • CD8 • HIF1A • IL1B • PTPRC

Multicenter phase 2 study of subcutaneous isatuximab plus bortezomib , lenalidomide and dexamethasone (Isa Sc-VRd) in transplant ineligible newly diagnosed multiple myeloma: Final analysis of the isasocut study (IFM 2022-05) (ASH 2025) - "The ISASOCUT study met its primary endpoint, confirming the efficacy and safety of Isa SC-VRd. These results support Isa SC-VRd as a new SOC in NDMM TI, offering a less intensive and moreconvenient option compared to IV-based regimens such as IMROZ"

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Transplantation

Global Access to Multiple Myeloma Medications (GLAMM-2 Study): Access and Barriers to Chemoimmunotherapies and Transplant (ASH 2023) - "Of the therapies listed, 6 were adequately available in LIC and HIC: cyclophosphamide, lenalidomide, pomalidomide, daratumumab, bortezomib, and ASCT (Table 1)...Conclusion While most therapies were available, novel therapies such as isatuximab, ixazomib, selinexor, and elotuzumab were less readily accessible...The financial burden on healthcare is a major limiting factor. USMIRC plans to investigate potential solutions and pursue global collaborative efforts to reduce disparities in therapies."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Isatuximab for Refractory Primary FSGS (KIDNEY WEEK 2025) - "He achieved partial remission with steroids, tacrolimus, and mycophenolate mofetil (MMF), and eventually stabilized on prednisone and tacrolimus, with losartan, empagliflozin, spironolactone, and atorvastatin...After rituximab induction, UPCR was 3.14, albumin 3 g/dL...CD-38 targeting antibodies such as isatuximab have been studied in the treatment of immune-mediated diseases, including primary FSGS, demonstrating either total remission or improvement in disease severity in cases refractory to conventional therapies. Further research is needed to determine optimal treatment regimens and dosing frequency, better study their efficacy, and the potential risk of adverse effects."

Chronic Kidney Disease • Focal Segmental Glomerulosclerosis • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Glomerulonephritis • Immunology • Nephrology • Renal Disease • Sarcoma

CD38KO/CD38-CAR Human Primary Natural Killer Cells Enhance Cytotoxicity Against CD38-Expressing Primary Lymphoma, Leukemia, and Myeloma (ASH 2023) - "FDA approved CD38 monoclonal antibodies (mAb) daratumumab and isatuximab are used to treat MM in patients, and have been tested to treat other CD38 expressing malignancies...Here, we generated multiple CD38 scFv based on isatuximab sequences and generated fratricide-resistant primary CD38-CAR NK cells using CRISPR/Cas9 genome editing and AAV6 gene delivery...Finally, we investigated the need for a CD38KO to develop a fratricide-resistant therapy by comparing the cytolytic and metabolic functions of CD38+/AAVS1KO and CD38KO CD38-CAR NK cells. We conclusively report a CD38-CAR NK cell therapy with enhanced metabolism and cytotoxicity toward a variety of hematologic malignancies, which can be further augmented by combination treatment with ATRA to target CD38-low malignancies."

IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Burkitt Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • CD38 • CD8

Trial in Progress: Phase 2 Study of Subcutaneous Isatuximab, Administered By an on-Body Delivery System, in Combination with Weekly Carfilzomib and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (SubQSA) (ASH 2024) - P1, P2 | "Intravenous (IV) Isa is currently approved to treat relapsed and/or refractory multiple myeloma (RRMM) in combination with pomalidomide and dexamethasone (Isa-Pd) or carfilzomib and dexamethasone (Isa-Kd)...In addition to dexamethasone, patients will receive premedication for IRs with montelukast (C1 only), acetaminophen, and diphenhydramine...ORR will be summarized with a two-sided 95% confidence interval by the Clopper-Pearson method. This study is not yet recruiting."

Clinical • Combination therapy • P2 data • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

Florida Cancer Specialists & Research Institute Clinical Expertise And Real-World Evidence Capabilities Advancing Treatment of Blood Cancers (PRNewswire) - "Physicians, clinicians, and senior leaders from Florida Cancer Specialists & Research Institute, LLC (FCS) are among the internationally recognized experts presenting advancements in the treatment of hematologic malignancies at the Society for Hematologic Oncology (SOHO) 2025 annual meeting this week in Houston."

Clinical data • Real-world • Melanoma • Multiple Myeloma • Myelodysplastic Syndrome • Myelofibrosis

Efficacy and safety of isatuximab subcutaneous (SC) plus carfilzomib and dexamethasone (Isa-Kd) in patients with relapsed/refractory multiple myeloma (RRMM): Results of the Phase 2 study IZALCO (JADPRO 2025) - "Introduction The anti-CD38 antibody isatuximab is approved in various countries for patients with relapsed/refractory multiple myeloma (RRMM) in combination with pomalidomide and dexamethasone (Pd) and with carfilzomib and dexamethasone (Kd)...RESULTS Of the 68 patients with RRMM enrolled and treated, the median number of prior lines of therapy was 2 (range, 1-8), and 42% were refractory to lenalidomide, 34% to bortezomib, and 44% were refractory to both (Table 1)...The majority of HCPs preferred the SC delivery method (100%) for injection of isatuximab. The SC administration of isatuximab is a convenient delivery option that could overcome some of the concerns about IV administration, and it may impact the SC delivery model (manual or delivery device) on isatuximab efficacy, safety, or patient preference."

Clinical • P2 data • Acute Kidney Injury • Cardiovascular • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Nephrology • Pneumonia • Renal Disease • Respiratory Diseases • Septic Shock

Isatuximab (Isa) subcutaneous (SC) via an on-body delivery system (OBDS) vs Isaintravenous (IV), plus pomalidomide and dexamethasone (Pd) in relapsed/refractorymultiple myeloma (RRMM): Results of the randomized, non-inferiority, Phase 3 IRAKLIAstudy (JADPRO 2025) - P3 | "IRAKLIA is the first RRMM Phase 3 trial to fully incorporate the use of an investigational OBDS, designed to maximize practice efficiency, and patient experience. These data support Isa SC OBDS as a standard of care administration for patients with MM."

Clinical • Head-to-Head • P3 data • Hematological Malignancies • Multiple Myeloma

Multicenter evaluation of soluble CD38: neutralizing anti-CD38 pan-reactivity to enable alloantibody detection. (PubMed, Blood Transfus) - "sCD38 has demonstrated strong potential in neutralizing anti-CD38 drugs in the clinical setting. While tested against isatuximab and daratumumab, it could be a potentially universal solution. By mimicking CD38 antigen on red blood cells, sCD38 is likely to interact with a broad range of anti-CD38 antibodies, suggesting its possible applicability across various settings."

Journal • Hematological Disorders • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology

…Results from the phase 2 ISASOCUT trial (NCT05889221) presented at the 22nd International Myeloma Society Annual Meeting (Cancer Network) - "The median follow-up for response and minimal residual disease (MRD)-negativity rates was 11.73 months. The VGPR or better rate was 87.8% (95% CI, 78%-94%). MRD-negative rate at 10-5 was 35.1%, and at 10-6 was 27.0%. The stringent complete response (CR)/CR rate with MRD-negativity at 10-5 was 61%. The median time to a VGPR or better was 3.71 months (95% CI, 2.333-3.778)."

P2 data • Multiple Myeloma

Patient Perspectives from the Phase 3 IRAKLIA Study of Isatuximab (Isa) Subcutaneous (SC) via On-body Injector (OBI) vs Isa Intravenous (IV) in Relapsed/refractory Multiple Myeloma (RRMM) (IMS 2025) - P3 | "This present analysis details pt satisfaction with the two Isa delivery methods in IRAKLIA. 531 pts aged ≥18 years with ≥1 prior line of therapy were randomized 1:1 to Isa OBI (1400 mg) or Isa IV (10 mg/kg) weekly in C1, then every 2 weeks with pomalidomide-dexamethasone. During IRAKLIA, pts receiving Isa OBI reported experiencing numerically less discomfort, pain, and side effects, and more time savings, from the injection method than Isa IV. These data suggest Isa OBI pts were more satisfied with and more likely to recommend their therapy than Isa IV pts and support the feasibility of using the OBI for Isa SC administration.Table. Descriptive analyses among PEQ/PESQ responders%Agree/ strongly agreeBL OBIBL IVC5D15 OBIC5D15 IVOn study* OBIOn study* IVInjection methodDiscomfort35.848.613.816.30-13.88.3-22.5Painful41.239.36.910.40-7.06.3-15.2Side effects50.051.912.29.90-15.04.2-19.0Time..."

Clinical • P3 data • Hematological Malignancies • Multiple Myeloma

Isatuximab Subcutaneous via an On-body Injector Plus Pomalidomide-dexamethasone in Relapsed/refractory Multiple Myeloma: Subgroup Analysis by Prior Lines of Therapy from the Phase 3 IRAKLIA Trial (IMS 2025) - P3 | "Introduction: The international, non-inferiority, open-label IRAKLIA trial (NCT05405166) of isatuximab (Isa) subcutaneous (SC) vs intravenous (IV) + pomalidomide-dexamethasone (Pd) is the first Phase 3 trial of an innovative on-body injector (OBI) in relapsed/refractory multiple myeloma (RRMM) patients (pts), who have been previously exposed to lenalidomide (LEN) and a proteasome inhibitor; pts with 1 prior line of therapy (LOT) had to be LEN-refractory. In IRAKLIA, comparable results were observed between the Isa SC OBI + Pd and Isa IV + Pd arms regardless of the number of prior LOT, demonstrating efficacy of Isa-Pd in the ≥1 prior LOT and LEN-refractory settings. These findings support use of Isa SC administered by the novel OBI plus Pd in RRMM pts regardless of number of prior LOT.Table 1 prior LOT>1 prior LOT Isa SC OBI + PdIsa IV + PdIsa SC OBI + PdIsa IV + PdPts (%)N=76N=84N=187N=184ORR74767068≥CR16191921≥VGPR43544842Funding: Sanofi."

P3 data • Hematological Malignancies • Multiple Myeloma

Efficacy and Safety of Isatuximab Subcutaneous (SC) Plus Carfilzomib and Dexamethasone (Isa-Kd) in Patients With Relapsed/Refractory Multiple Myeloma (RRMM): Results of the Phase 2 Study IZALCO (IMS 2025) - P2 | "Results of a Phase 1b study demonstrated safety and efficacy of Isa SC administration via an on-body delivery system (OBDS; an investigational wearable injector), plus pomalidomide and dexamethasone in RRMM pts. The study met its primary endpoint, demonstrating efficacy, safety, and similar PK exposure of Isa SC administration in combination with Kd, either by manual injection or OBDS. Our study findings are consistent with those reported in the Phase 3 study IKEMA with intravenous Isa. Pts expressed a clear preference for receiving Isa SC by an OBDS.Funding: Sanofi."

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • AVEN

Isatuximab Subcutaneous (Isa SC) via On-Body Injector (OBI) or Manual Injection for Relapsed/Refractory Multiple Myeloma (RRMM): Patient Experience from the Phase 2 IZALCO Study (IMS 2025) - P2 | "The Phase 2 IZALCO study (NCT05704049) met its primary endpoint, demonstrating efficacy (ORR, 79.7%), safety and similar pharmacokinetic exposure for Isa SC administered via OBI or manual injection in combination with carfilzomib-dexamethasone in RRMM patients. In IZALCO, treatment with Isa SC administered via OBI or manual injection alleviated initial patient concerns about discomfort, pain and side effects, and resulted in a high proportion of patients reporting satisfaction. These findings complement the patient preference data reported for Isa OBI vs manual injection and suggest that the OBI is a convenient option for Isa SC administration. Funding: Sanofi."

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma

Isatuximab Subcutaneous via an on-body Delivery System versus Isatuximab Intravenous, Plus Pomalidomide and Dexamethasone, in Relapsed/Refractory Multiple Myeloma: The Randomized Phase 3 IRAKLIA Study (IMS 2025) - P3 | "IRAKLIA showed efficacy and pharmacokinetic NI between Isa SC vs IV. No new safety signal besides low ISR incidence was observed, showing excellent Isa SC local tolerability with OBDS. Far fewer infusion reactions and higher pt satisfaction were also noted for SC vs IV."

Clinical • P3 data • Hematological Malignancies • Multiple Myeloma

Multicenter Phase 2 Study of Subcutaneous Isatuximab Plus Bortezomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Transplant-Ineligible Multiple Myeloma: Results from ISASOCUT (IFM 2022-05) (IMS 2025) - "The ISASOCUT study met its primary endpoint, demonstrating consistent efficacy of isatuximab in NDMM TI patients, regardless of SC or IV administration. These results support Isa SC-VRd as a new SOC for NDMM TI, offering a longer but less dose-intensive induction regimen compared to IMROZ."

Clinical • P2 data • Hematological Malignancies • Multiple Myeloma • Transplantation

Single-Cell Immune Landscape Associated with Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone Induction Efficacy in Newly Diagnosed Myeloma (IMS 2025) - "Introduction: Quadruplet regimens combining CD38-targeting monoclonal antibodies, such as Isatuximab or Daratumumab, with proteasome inhibitors, immunomodulatory drugs (IMiDs), and dexamethasone have recently emerged as the standard-of-care induction therapy for newly diagnosed multiple myeloma (NDMM). Our study provides a comprehensive single-cell atlas of the immune microenvironment in NDMM patients before and after IsaKRD induction. We reveal coordinated reshaping of both lymphoid and myeloid compartments, with immune signatures that correlate with MRD status and treatment efficacy. These findings underscore the importance of immune remodeling in shaping therapeutic outcomes and offer potential avenues for biomarker development and immune-based interventions in multiple myeloma."

Clinical • IO biomarker • Hematological Malignancies • Multiple Myeloma

Trial in Progress: Phase 2 SubQSA Study of Subcutaneous (SC) Isatuximab (Isa) Administered by an On-Body Delivery System (OBDS) in Combination With Weekly Carfilzomib and Dexamethasone (Kd) in Patients with Relapsed/ Refractory Multiple Myeloma (RRMM) (SOHO 2025) - P1, P2 | "Context: Isa intravenous (IV), plus pomalidomide-dexamethasone (Pd) or Kd, is approved for RRMM."

Clinical • Combination therapy • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Erratum: Isatuximab Subcutaneous by On-Body Injector Versus Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase III IRAKLIA Study. (PubMed, J Clin Oncol) - No abstract available

Journal • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology