isatuximab subcutaneous (SAR650984 SC) / Sanofi - LARVOL DELTA

On 26 March 2026, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending a change to the terms of the marketing authorisation for the medicinal product Sarclisa. (European Medicines Agency) - "Isatuximab is indicated: in combination with pomalidomide and dexamethasone, for the treatment of adult patients with relapsed and refractory multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on the last therapy; in combination with carfilzomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy; in combination with bortezomib, lenalidomide, and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; in combination with bortezomib, lenalidomide, and dexamethasone, for the induction treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant."

CHMP • Multiple Myeloma

Study of Selinexor With Carfilzomib, Isatuximab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1/2 | N=62 | Not yet recruiting | Sponsor: Natalie Callander

New P1/2 trial • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • TP53

Isatuximab (Isa) subcutaneous (SC) via an on-body delivery system (OBDS) vs Isa intravenous (IV), plus pomalidomide and dexamethasone (Pd) in relapsed/refractory multiple myeloma (RRMM): Results of the randomized, non-inferiority, phase 3 IRAKLIA study. (ASCO 2025) - P3 | "IRAKLIA met its co-primary endpoints, showing efficacy and pharmacokinetic NI between Isa SC vs IV + Pd. No new safety signal besides a low ISR incidence was observed, showing excellent Isa SC tolerability. Far fewer infusion reactions and higher pt satisfaction were also noted for SC vs IV."

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

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. (ASCO 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 and safety of Isa SC administration in combination with Kd, either by manual injection or OBDS. Our study findings are comparable to those reported in the Phase 3 study IKEMA with Isa IV. Pts expressed a clear preference for receiving Isa SC by an OBDS."

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

Efficacy and safety of isatuximab subcutaneous plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma: results of the Phase 2 study IZALCO. (PubMed, Blood Cancer J) - P2 | "No impact of the SC delivery method was observed on efficacy, safety, pharmacokinetics, and immunogenicity of isatuximab given SC plus Kd, supporting the feasibility of using the OBI as a convenient method for isatuximab SC administration. Clinical trial information: ClinicalTrials.gov NCT05704049."

Journal • P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

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

ELISA in Relapsed/Refractory MM (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Massachusetts General Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Isatuximab Subcutaneous by On-Body Delivery System vs Isatuximab Intravenous Plus Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma: Phase 3 IRAKLIA Study. (PubMed, J Clin Oncol) - P3 | "Efficacy and safety were comparable to isatuximab IV in ICARIA-MM, except the lower OBDS infusion reaction rate. These results support potential use of the OBDS, designed to improve practice efficiency."

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

Evolving understandings for the roles of CD38 protein in autoimmunity and autoimmune disease. (PubMed, Clin Exp Immunol) - "CD38-targeted monoclonal antibodies with favorable therapeutic effects have been discovered, such as isatuximab, daratumumab, and mezagitamab. CD38 protein is a promising biomarker of autoimmune diseases diagnosis and a potential therapeutic target for the treatment of autoimmune diseases. In this review, we will focus on the latest findings on the involvement of CD38 in autoimmunity and autoimmune disease, and assess the value of research and application of CD38 in disease control."

IO biomarker • Journal • Hematological Malignancies • Immunology • Inflammation • Multiple Myeloma • Oncology

GMMG-HD8/DSMM XIX: A randomized phase III non-inferiority trial assessing lenalidomide, bortezomib and dexame-thasone induction therapy with either intravenous or subcutaneous isatuximab in patients with newly diagnosed multiple myeloma (clinicaltrialsregister.eu) - P2/3 | N=514 | Completed | Sponsor: | Active, not recruiting ➔ Completed

Head-to-Head • Trial completion • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Time and Resource Implications of Subcutaneous Daratumumab-Based versus Intravenous Isatuximab-Based Treatment Regimens for Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Ineligible. (PubMed, Oncol Ther) - "This study demonstrated notable time savings with daratumumab SC-based versus isatuximab IV-based regimens in patients with newly diagnosed MM who are transplant ineligible based on SC versus IV administration and less frequent daratumumab dosing."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Patients With Newly Diagnosed Multiple Myeloma (clinicaltrials.gov) - P3 | N=514 | Completed | Sponsor: University of Heidelberg Medical Center | Active, not recruiting ➔ Completed | Trial completion date: Jul 2026 ➔ Jan 2026 | Trial primary completion date: Jul 2025 ➔ Jan 2026

Head-to-Head • Trial completion • Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

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 (EHA 2025) - P3 | "IRAKLIA met its co-primary endpoints, showing efficacy and pharmacokinetic non-inferiority of Isa SC OBDS compared with Isa IV, plus Pd. No new safety signal besides a low ISR incidence was observed, showing excellent tolerability of Isa SC OBDS. Far fewer infusion reactions and a higher patient satisfaction were also noted for Isa SC OBDS compared with Isa IV."

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

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

Subcutaneous isatuximab administration by an on-body delivery system in combination with pomalidomidedexamethasone in relapsed/refractory multiple myeloma patients: interim phase 1b study results (IMW 2022) - P1b | "Introduction: Intravenous (IV) isatuximab (Isa) + pomalidomide-dexamethasone (Pd) is approved for treatment of relapsed/refractory multiple myeloma (RRMM) patients (pts). SC Isa administered by OBDS shows safety profile consistent with IV administration with no IRs and excellent local tolerability. Efficacy in SC cohorts was comparable to Phase 3 ICARIA results. PK results in OBDS pts were similar to those receiving SC1400."

Clinical • Combination therapy • P1 data • Anemia • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology

Subcutaneous Isatuximab Administration By an on-Body Delivery System (OBDS) in Combination with Pomalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Phase 1b Expansion Study Results (ASH 2022) - P1b, P3 | "These updated results with longer follow-up of SC Isa administration via OBDS at the RP2D of 1400 mg showed a safety profile consistent with IV administration, with no IRs, excellent local tolerability and efficacy comparable to that observed in the phase 3 ICARIA study with IV Isa, in combination with Pd. Isa SC administration by OBDS is well tolerated, has a short duration of injection, and provides a convenient hands-free option with controlled delivery. Based on these results and OBDS performance, a non-inferiority phase 3 trial of Isa-SC with OBDS versus Isa-IV is ongoing (NCT05405166)."

Clinical • Combination therapy • P1 data • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • CD38

Bone Marrow Immune Signatures in Multiple Myeloma Are Linked to Tumor Heterogeneity and Treatment Outcome (ASH 2022) - P3 | "Anti-CD38 monoclonal antibodies increase efficacy when added to standard-of-care (SOC) regimens as reflected by minimal residual disease-negativity (MRD-neg) rates of >50 % after induction therapy in newly diagnosed MM (NDMM) patients treated with SOC plus isatuximab within the GMMG-HD7 trial (Goldschmidt et al...NDMM patients were treated with lenalidomide/bortezomib/dexamethasone (RVd) alone or in combination with isatuximab (isa-RVd, NCT03617731)...BME signatures at baseline and during treatment as defined by our reference atlas enable risk stratifications of MM patients and can identify patients at high risk for early relapse. Longitudinal monitoring of the BME can support clinical decision making, as a compromised CD8+ memory compartment in patients may impact on the efficacy of novel immunotherapies."

Clinical • Heterogeneity • IO biomarker • Bone Marrow Transplantation • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology • Transplantation • CD4 • CD8 • NRAS

IZALCO: A Study to Investigate Subcutaneous Isatuximab in Combination With Carfilzomib and Dexamethasone in Adult Participants With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Hematological Malignancies • Multiple Myeloma • Oncology

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

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