Sarclisa (isatuximab-irfc) / Sanofi, AbbVie - LARVOL DELTA

MRD-driven strategy following IsaKRD induction in transplant-eligible NDMM: Primary endpoints of the phase 3 MIDAS trial. (ASCO 2025) - P3 | "Funded by No funding sources reported Clinical Trial Registration Number: NCT04934475 Background: The phase III IFM2020-02-MIDAS study (NCT04934475) evaluated a minimal residual disease (MRD)-driven consolidation and maintenance strategy following induction with isatuximab, carfilzomib, lenalidomide, and dexamethasone (IsaKRD) in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM)...MRD-positive patients after induction (MRD ≥10⁻⁵) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance... After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10⁻⁵, MRD negativity rates at 10⁻⁶ before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10-5, tandem ASCT did not significantly improve MRD negativity rates at 10⁻⁶..."

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

Steroid-toxicity in newly diagnosed patients with multiple myeloma treated with a limited dexamethasone regimen; Results from the nmsg rest study (ASH 2025) - "Patients were treated with isatuximab-bortezomib-lenalidomide-dexamethasone; dexamethasone was omitted after two cycles, bortezomib was omittedafter eight cycles and isatuximab was omitted after 18 cycles. Steroids are included in most myeloma-targeted therapies. However, growing evidenceshows similar disease responses with steroid-limited treatments. Overall, we found a statisticalsignificant difference in steroid toxicity during cycles with dexamethasone compared to cycles withoutdexamethasone."

Clinical • Anorexia • CNS Disorders • Hematological Malignancies • Insomnia • Multiple Myeloma • Sleep Disorder

Sustained minimal residual disease (sMRD) negativity in transplant ineligible newly diagnosed multiple myeloma treated with isatuximab plus lenalidomide and dexamethasone with bortezomib (Isa-VRd) versus isa-rd: 12-24-month data from the phase 3 benefit trial (IFM 2020-05) (ASH 2025) - P3 | "The BENEFIT study continues to support the efficacy of the quadruplet Isa-VRd regimen inNDMM TI patients, notably through improved sustained MRD negativity rates. These data support Isa-VRdas a new standard of care (SOC) for NDMM TI patients aged 65–79 years, including those with HRMM.ClinicalTrials.gov Identifier: NCT04751877"

Minimal residual disease • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Transplantation

An immune-therapeutic salvage strategy for 'functional' high-risk (FHR) multiple myeloma (MM) incorporating iberdomide, isatuximab, and dexamethasone – the IBIS study amarc 20-01. (ASH 2025) - P2 | "Of 50 pts: 28%, 32%, 16%, 12% with 0, 1, 2 or 3 high-risk chromosomal abnormalitiesrespectively; 34% fulfilling IMS2025 high-risk criteria, 54% standard-risk and 12% in whom diagnosticCG/FISH were omitted, 83% received PI-IMID 1L (76% VRd, 3% VRd+chemotherapy, 7% VRd+Selinexor),10% bortezomib-cyclophosphamide-dexamethasone (VCD), 7% lenalidomide-dexamethasone (Rd), 24%ASCT; 10% 1REF to 1L and 90% relapsed after initial response to 1L, of these 72% had ³PR to 1L. In this second planned interim analysis, IB-IS-DEX was well-tolerated, achieved early diseasecontrol and demonstrated promising efficacy in FHR MM. Preliminary ctDNA genomic analyses highlight asubstantial burden of adverse biology, with frequent del(17p), MYC copy number gains, and high cTFamong pts with PD. Updates on survival will be presented at the conference."

CNS Disorders • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Insomnia • Multiple Myeloma • Neutropenia • Respiratory Diseases • Septic Shock • Sleep Disorder • Squamous Cell Carcinoma

Disproportionality analysis of drug-associated progressive multifocal leukoencephalopathy: roles of underlying diseases and immunomodulatory therapies in FAERS. (PubMed, Front Immunol) - "Fifty-four drugs showed significant signals in primary analysis with the exception of acalabrutinib in the analysis restricted to 6,258 cases, including established high-risk agents and potential novel associations. Notably, we observed signals with four monoclonal antibodies (daratumumab, elotuzumab, epcoritamab, and isatuximab); isatuximab had no previous mentions in regulatory labels or published literature to our knowledge. Among established agents, natalizumab had the highest number of reports (n=1,848; ROR 40.7), and rituximab also showed a strong signal (n=1,296; ROR 41.8)...Median TTO for antineoplastic drugs (13.6 months; 95% CI: 11.5-15.9) was significantly shorter than for non-antineoplastic drugs (42.4 months; 95% CI: 39.7-44.1). These findings reinforce established and emerging PML reporting signals with immunomodulatory therapies and support heightened pharmacovigilance-particularly for novel monoclonal antibodies used in hematologic malignancies."

Journal • B Cell Non-Hodgkin Lymphoma • CNS Disorders • Hematological Disorders • Hematological Malignancies • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Oncology • Rare Diseases

Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. (PubMed, N Engl J Med) - P3 | "Isatuximab-VRd was more effective than VRd as initial therapy in patients 18 to 80 years of age with newly diagnosed multiple myeloma who were ineligible to undergo transplantation. (Funded by Sanofi and a Cancer Center Support Grant; IMROZ ClinicalTrials.gov number, NCT03319667.)."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Low conversion rates to minimal residual disease (MRD) negativity despite improved IMWG responses with lenalidomide-isatuximab maintenance after autologous stem cell transplant (ASCT) in multiple myeloma. (ASH 2025) - P2 | "More than half of the patients showed an improvement in IMWG response, with doubletmaintenance of lenalidomide and CD38 MoAb in patients with persistent MRD following ASCT in thispatient population, which was enriched for high-risk disease and predominantly received a quadrupletCD38 MoAb-based induction regimen. There is thus significant potential for continued exploration ofnovel approaches, including CAR T-cell therapy and bispecific antibodies, to further enhance responses inpatients with persistent MRD."

Clinical • IO biomarker • Minimal residual disease • Residual disease • Back Pain • Constipation • Gastroenterology • Gastrointestinal Disorder • Genito-urinary Cancer • Hematological Malignancies • Hypertension • Infectious Disease • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Prostate Cancer • Respiratory Diseases • Solid Tumor • Thyroid Gland Carcinoma • Thyroid Gland Papillary Carcinoma • Transplantation • CD4 • PD-L1

Double hit ultra-high risk myeloma treated with isatuximab, bortezomib, lenalidomide, dexamethasone and cyclophosphamide (Isa-VRDc) induction and isa-VRD consolidation: Initial results of the UK myeloma research alliance (UKMRA) RADAR trial in newly diagnosed transplant eligible patients (ASH 2025) - "RADAR HRv4 pathway is the largest analysis of ultra-high risk (double hit) patients reportedto date. All participants meet the new IMS/IMWG HR criteria. Isa-VRDc induction, followed by Isa-VRDconsolidation post-ASCT and IsaR maintenance met the primary endpoint, with the study crossing theGreen design threshold, with 88% (59/67) alive and progression-free at 18 months."

Clinical • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Transplantation

Health-related quality of life (HRQoL) in patients with newly diagnosed multiple myeloma (NDMM) eligible for transplantation and treated with isatuximab, lenalidomide, bortezomib, and dexamethasone (Isa-RVd) versus rvd alone: Results from part 1 of the GMMG-HD7 study (ASH 2025) - P3 | "This enhanced efficacy is observed withoutcompromising overall HRQoL, and importantly, is associated with significant improvement in fatigue anda favorable trend in pain reduction, compared to RVd alone. These findings underscore the favorablebenefit-risk profile and value of Isa-RVd quadruplet for transplant eligible NDMM pts."

Clinical • HEOR • Hematological Malignancies • Multiple Myeloma • Transplantation

GRAAL-2024: A 3-cohort Randomized Study Evaluating the Role of New Immunotherapeutic Agents and of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) in Frontline Therapy of Adults With Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P2/3 | N=1200 | Recruiting | Sponsor: Assistance Publique - Hôpitaux de Paris | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Transplantation

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

Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma. (PubMed, N Engl J Med) - P3 | "Among patients who were MRD-negative at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with ASCT than with Isa-KRd. Among patients who were MRD-positive status at 10-5 sensitivity after induction, the percentage with a premaintenance MRD-negative status at 10-6 sensitivity was not significantly higher with tandem ASCT than with single ASCT. (Funded by Intergroupe Francophone du Myélome and others; MIDAS ClinicalTrials.gov number, NCT04934475.)."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Efficacy and Safety of Newly Diagnosed Multiple Myeloma Combination Therapies: A Systematic Review Integrating Network Meta-Analysis and Real-World Vigilance Study. (PubMed, Pharmaceuticals (Basel)) - "Separately, adverse event reports for daratumumab, bortezomib, lenalidomide, and dexamethasone (D_VRd) regimens were extracted from the US FDA Adverse Event Reporting System (FAERS) (Q1 2015-Q2 2025)...For the primary efficacy endpoints, compared to the standard bortezomib, lenalidomide, and dexamethasone (VRd) regimen, both D_VRd (OR = 3.21, 95% CI: 2.46-4.26; HR = 0.48, 95% CI: 0.38-0.63) and isatuximab plus VRd (Isa_VRd) (OR = 1.71, 95% CI: 1.25-2.32; HR = 0.66, 95% CI: 0.51-0.85) regimens demonstrated superior efficacy...Real-world data analysis further indicates that the D_VRd regimen carries several safety risk signals that remain underappreciated and exhibits a bimodal time distribution pattern. These findings provide new evidence to guide clinical decision-making and risk-stratified monitoring."

Journal • Real-world evidence • Retrospective data • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Single-molecule localization microscopy reveals the molecular organization of endogenous membrane receptors. (PubMed, Sci Adv) - "To demonstrate the usefulness of the method for immunotherapy applications, we investigated the interaction of primary multiple myeloma cells with the therapeutic monoclonal antibodies daratumumab and isatuximab and a polyclonal anti-CD38 antibody. Our approach might lay the foundation for improved personalized diagnostics and treatment with therapeutic antibodies."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CD69 • PTPRC

Addition of anti-CD38 mAb in newly diagnosed multiple myeloma: advancing toward quadruplet induction regimens. (PubMed, Blood Neoplasia) - "We conducted a systematic search of the Cochrane Library, PubMed, Embase, Scopus, and Web of Science databases to identify studies comparing induction regimens with and without anti-CD38 monoclonal antibodies (daratumumab or isatuximab) and assessed the efficacy and safety of anti-CD38-based induction regimens in NDMM. Grade 3 or 4 infections and hematologic toxicities occurred more frequently with anti-CD38 regimens. In summary, anti-CD38-based induction improves depth of response and PFS across NDMM populations, including high-risk disease, with increased but manageable toxicity."

Journal • Review • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Transplantation

Elotuzumab in combination with pomalidomide, bortezomib, and dexamethasone in relapsed and refractory multiple myeloma. (PubMed, Blood Adv) - "Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM)...Prior therapies included: pomalidomide (33%), daratumumab (25%), and isatuximab (4%)...Common grade ≥3 adverse events were neutropenia (33%); infections, any (33%); lung infection (27%); hypophosphatemia (19%); and thrombocytopenia (15%). Elo-PVd is one of the first trials of a quadruplet regimen in relapsed/refractory MM incorporating a monoclonal antibody to show efficacy across diverse prior treatments, including triple class exposed with prior anti-CD38 monoclonal antibody."

Combination therapy • Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Renal Disease • Respiratory Diseases • Thrombocytopenia • SLAMF7

Thromboembolism in transplant-ineligible multiple myeloma patients on triplet/quadruplet therapy: a post-hoc analysis of BENEFIT. (PubMed, J Thromb Haemost) - P3 | "In summary, the cumulative incidence of VTE remains high in patients with TI nMM. DOACs could be the most effective option for preventing VTE."

Journal • Retrospective data • Cardiovascular • Hematological Malignancies • Multiple Myeloma • Oncology • Renal Disease • Transplantation • Venous Thromboembolism

GMMG-HD7: Trial on the Effect of Isatuximab to Lenalidomide/Bortezomib/Dexamethasone (RVd) Induction and Lenalidomide Maintenance in Patients With Newly Diagnosed Myeloma (GMMG HD7) (clinicaltrials.gov) - P3 | N=662 | Active, not recruiting | Sponsor: University of Heidelberg Medical Center | Trial completion date: Mar 2027 ➔ Jun 2028 | Trial primary completion date: May 2025 ➔ Jun 2028

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Isatuximab, carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) for high-risk (HR) newly diagnosed multiple myeloma (NDMM): First-time report of the full cohort of transplant-eligible (TE) patients in the GMMG-CONCEPT trial. (ASCO 2025) - P2 | "The full CONCEPT cohort represents the largest prospective trial cohort of purely HR NDMM pts reported so far. Isa-KRd resulted in unprecedented rates of MRD-neg., sustained MRD-neg. and survival supporting the use of Isa-KRd as a standard-of-care regime in this hard-to-treat population."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Sarclisa (multiple myeloma) sales were €157 million and increased by 27.7%, supported by high growth in all regions mainly from increased use in the transplant-ineligible, front-line combination treatment setting based on results in the IMROZ phase 3 study. (GlobeNewswire)

Sales • Multiple Myeloma

MINIMAL RESIDUAL DISEASE-DRIVEN STRATEGY FOLLOWING ISATUXIMAB-CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE INDUCTION IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PRIMARY ENDPOINTS OF THE PHASE 3 MIDAS TRIAL (EHA 2025) - P3 | "MRD- positive patients after induction (MRD ≥10−5) were randomized to either single ASCT plus 2 cycles of IsaKRD (Arm C) or tandem ASCT (Arm D) followed by isatuximab plus iberdomide maintenance. After 6 induction cycles with IsaKRD, in patients who achieved MRD negativity at 10−5, MRD negativity rates at 10−6 before maintenance were not significantly different between the transplant-based approach and IsaKRD consolidation alone, whereas in patients who do not achieve MRD negativity at 10-5, tandem ASCT did not significantly improve MRD negativity rates at 10−6 before maintenance. Further follow-up, including sustained MRD negativity and PFS data, is needed to evaluate the long-term outcomes of this MRD-adapted strategy."

Minimal residual disease • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Dual Targeting of Slamf-7 and CD38 in Mulitple Myeloma (MM): A Phase II Study of Isatuximab, Elotuzumab, Pomalidomide and Dexamethasone (Isa-EloPD) in Relapsed and/or Refractory MM (RRMM) (ASH 2023) - P2 | "Disease was refractory to lenalidomide in all patients, and refractory to both bortezomib and lenalidomide in 3 patients. This is the first ever report combining two different mAbs with dual targeting of CD38 and SLAMF7 in RRMM. The results demonstrate that Isa-EloPD combination is both safe and feasible with high frequency and durability of responses. Despite an anticipated reduction in number, NK cell cytotoxicity remain unaffected with the combination."

IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • SLAMF7

A multicenter prospective randomized controlled study of quadruplet regimen in newly diagnosed transplant-ineligible high-risk multiple myeloma patients (ChiCTR) - P4 | N=117 | Not yet recruiting | Sponsor: Peking Union Medical College Hospital; Peking Union Medical College Hospital

New P4 trial • Anemia • Endocrine Disorders • Fatigue • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Oncology • Renal Disease • Transplantation • TP53

The addition of CD38 monoclonal antibody to triplet regimens improves survival in newly diagnosed multiple myeloma with high-risk cytogenetics: a systematic review and meta-analysis of randomized controlled trials. (PubMed, Front Immunol) - "However, subgroup analyses revealed that the PFS benefit was not significant for isatuximab-based quadruplet regimens (pooled HR = 1.04, 95% CI: 0.67-1.62, P = 0.84) or in transplant-ineligible patients (pooled HR = 0.79, 95% CI: 0.56-1.13, P = 0.19). The incorporation of CD38 mAbs, particularly daratumumab, into triplet regimens improves depth of response and PFS in NDMM patients with high-risk cytogenetics. https://inplasy.com/inplasy-2025-10-0103/ , identifier INPLASY2025100103."

Clinical • Journal • Retrospective data • Review • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial. (PubMed, J Clin Oncol) - P3 | "Weighted risk set estimator analysis accounting for second random assignment followed by maintenance with only lenalidomide confirmed a statistically significant benefit for Isa-RVd followed by lenalidomide maintenance versus RVd followed by lenalidomide maintenance (stratified weighted log-rank test P = .016). In conclusion, after 18-week induction therapy followed by transplant without consolidation therapy, adding Isa to RVd resulted in a significant PFS benefit, regardless of maintenance strategy."

Journal • Bone Marrow Transplantation • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation