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

Isatuximab for the treatment of multiple myeloma: current clinical advances and future directions. (PubMed, Expert Opin Investig Drugs) - "Further, we address current approaches to optimize treatment with isatuximab-based combinations involving changes in bortezomib or dexamethasone dosing. Lastly, we review current findings with new administration modalities developed to optimize delivery of isatuximab in the clinic. Supported by multiple lines of high-level evidence, isatuximab in combination with standard-of-care backbone therapies produces triplet or quadruplet regimens with enhanced efficacy and consistent safety for the treatment of patients with NDMM and RRMM."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Autoimmune complications of lymphoproliferative diseases (ICML 2025) - "Moreover, several drugs may be responsible for immune-mediated cytopenias, including several antibiotics (ceftriaxone, piperacillin, rifampin, nafcillin, erythromycin, ticarcillin, trimethoprim, sulfamethoxazole), and various other drugs (procainamide, quinine, phenacetin, diclofenac, cimetidine, hydrochlorothiazide, chlorpropamide) [8]...Ibrutinib, through the inhibition of autoantibodies producing B-cells and restoration of T-cell homeostasis seems safe, while some case reports of autoimmune diseases have been reported for idelalisib (autoimmune hepatitis, colitis) and venetoclax (AIHA) [5, 6]...They included nivolumab, followed by pembrolizumab, ipilimumab, and atezolizumab...In particular, in CLL several therapies have been reported effective in refractory cytopenias: alemtuzumab single agent, the combinations ibrutinib-rituximab, bendamustine-rituximab, and rituximab–cyclophosphamide-dexamethasone [34-37]. Notably, some of the new/experimental treatments for primary..."

IO biomarker • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Lymphoplasmacytic Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • CTLA4 • HP • IL10 • PD-1 • TGFB1

Horizon Two Adaptive Platform Study in High Risk Newly Diagnosed Multiple Myeloma (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: Multiple Myeloma Research Consortium

New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

A Rare Case of Pseudohypercalcemia Associated with Multiple Myeloma. (PubMed, Kobe J Med Sci) - "Treatment with isatuximab plus dexamethasone normalized albumin-corrected calcium levels as IgG levels decreased. This report highlights the importance of recognizing pseudohypercalcemia to prevent misdiagnosis of true hypercalcemia due to myeloma. Measuring ionized calcium levels is crucial for accurate diagnosis when hypercalcemia is suspected without corresponding clinical symptoms."

Journal • Endocrine Disorders • Hematological Malignancies • Metabolic Disorders • Multiple Myeloma • Oncology

Cardiac biomarkers for risk stratification in newly diagnosed high-risk multiple myeloma in the GMMG-CONCEPT trial. (PubMed, Cardiooncology) - P2 | "We investigated the predictive value of cardiac biomarkers for onset of CVAE in patients with newly diagnosed high-risk multiple myeloma treated with isatuximab, carfilzomib, lenalidomide, and dexamethasone in the GMMG-CONCEPT study (NCT03104842). Patients with hsTropI level ≥ 2.9 ng/L, corresponding to the lower limit of quantification, showed a higher risk for CVAE compared to patients with hsTropI < 2.9 ng/L at baseline (p = 0.0023). In conclusion, in patients with newly diagnosed high-risk multiple myeloma undergoing carfilzomib-based quadruplet treatment, low hsTropI pretreatment levels are of high negative predictive value for the occurrence of CVAE whereas elevated NT-proBNP levels are very common before treatment initiation."

Biomarker • Journal • Cardiovascular • Hematological Malignancies • Multiple Myeloma • Oncology

Subcutaneous administration of isatuximab in patients with multiple myeloma by an on-body delivery system: results of a nurse survey. (PubMed, Front Oncol) - "Subcutaneous (SC) administration of the anti-CD38 antibody isatuximab (Isa) by an on-body delivery system (OBDS), plus pomalidomide-dexamethasone, has demonstrated safety and efficacy comparable to intravenous (IV) administration, with no infusion reactions and excellent local tolerability in multiple myeloma (MM) patients. Our findings show a high level of confidence among nurses in SC Isa administration via OBDS, due to the ease of use, tolerability, and time savings achieved with hands-free OBDS injections. Our findings suggest applicability of the OBDS for convenient SC Isa administration to MM patients in routine clinical practice."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Pain

A retrospective study of isatuximab-pomalidomide-dexamethasone in relapsed/refractory systemic AL amyloidosis. (PubMed, Haematologica) - "Not available."

Journal • Retrospective data • Amyloidosis

Positive Results Reported With Isa-KRd in High-Risk, Newly Diagnosed MM (Hematology Advisor) - P2 | N=246 | CONCEPT (NCT03104842) | "Phase 2 trial results support isatuximab plus carfilzomib, lenalidomide, and dexamethasone (Isa-KRd) as a standard treatment option for patients with high-risk, newly diagnosed multiple myeloma (MM), according to a presentation at the EHA 2025 Congress...This phase 2 trial — CONCEPT (NCT03104842) — included 219 patients with newly diagnosed, transplant-eligible MM who had 1 or more high-risk features. The trial also included 26 patients with newly diagnosed, transplant-ineligible MM...The primary endpoint was minimal residual disease (MRD) negativity at the end of consolidation (10-5). At that time, 74.8% of transplant-eligible patients and 54.2% of transplant-ineligible patients were MRD negative....The proportion of patients who achieved MRD negativity at any time was 86.8% in the transplant-eligible cohort and 69.2% in the transplant-ineligible cohort."

P2 data • Multiple Myeloma

Efficacy and Safety of Anitocabtagene Autoleucel in Participants With Newly Diagnosed Multiple Myeloma (GEM-AnitoFIRST) (clinicaltrials.gov) - P2 | N=30 | Not yet recruiting | Sponsor: PETHEMA Foundation

New P2 trial • Hematological Malignancies • Multiple Myeloma • Oncology

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), the NCCN Drugs & Biologics Compendium (NCCN Compendium), the NCCN Radiation Therapy Compendium, and the NCCN Imaging Appropriate Use Criteria (NCCN Imaging AUC) for Multiple Myeloma, Version 1.2026. (NCCN)

NCCN guideline • Multiple Myeloma

Single-cell transcriptomic landscape indicates the potential role of immunotherapy in metastatic pancreatic angiosarcoma. (PubMed, Gastroenterol Rep (Oxf)) - "Our findings outlined an immunosuppressive and angiogenic tumor ecosystem in pancreatic angiosarcoma liver metastasis, suggesting that pancreatic angiosarcoma may be insensitive to most targeted therapies. Conversely, immunotherapies targeting LAG3, PD-L1, and CD86 (e.g. isatuximab, Opdualag, and abatacept) and anti-angiogenic agents may be therapeutically effective and worthy of subsequent exploration."

Journal • Angiosarcoma • Oncology • Pancreatic Cancer • Sarcoma • Solid Tumor • CD86 • CDK4 • CTLA4 • EGFR • HIF1A • LAG3 • PD-1

Treatment Patterns, Goals, and Decision-Making Criteria for Second- and Third-Line Therapies for Multiple Myeloma in Germany. (PubMed, Adv Ther) - "The results suggest that in the absence of a single standard of care for RRMM, prescribers made patient-centred choices of regimens with efficacy as the main goal of therapy."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Daratumumab and isatuximab differentially affect CD38 detection on plasma cells in myeloma: Anti-CD38 nanobody (clone JK36) and CD319 combination improve flow cytometric identification of plasma cells after targeted therapies. (PubMed, Br J Haematol) - "Interestingly, isatuximab showed an opposite pattern, with complete loss of CD38 detection by JK36, while retaining dim positivity by HB-7. This combination of markers proved highly effective in identifying abnormal PCs after CD38-directed therapies, supporting a need for redundancy of gating markers in FC panels."

IO biomarker • Journal • Hematological Malignancies • Multiple Myeloma • Oncology • PTPRC • SDC1 • SLAMF7

Sarclisa - opinion on variation to marketing authorisation (European Medicines Agency) - "On 19 June 2025, 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. The marketing authorisation holder for this medicinal product is Sanofi Winthrop Industrie. The CHMP adopted a new indication to include treatment of adults with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant."

CHMP • Multiple Myeloma

Risk adapted therapy for newly diagnosed multiple myeloma delivered through local cytogenetic laboratories in a National Clinical Trial: UKMRA RADAR study. (PubMed, EJHaem) - "We have observed excellent overall success rates, with > 90% patients assigned to a risk-adapted pathway following cytogenetic testing in 25 local laboratories nationwide, with clinically-relevant turnaround times allowing > 70% patients to commence isatuximab at the earliest opportunity if indicated. This paves the way for providing standard-of-care risk-adapted treatment for multiple myeloma patients in the UK."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

REAL-WORLD THERAPY INSIGHTS: PATIENT-REPORTED OUTCOMES & WEARABLE DATA IN UK MULTIPLE MYELOMA PATIENTS (EHA 2025) - "Treatments included maintenance lenalidomide (n=8), Panobinostat, Bortezomib and Dexamethasone (n=1), Isatuximab, Pomadlidomide and Dexamethasone (n=1) and maintenance daratumumab (n=1). This work establishes symptom profiles and demographic trends with real-world MM patient data using a selected set of PROs and biometrics. Early findings suggest potential links between symptom burden and wearable data, with initial observations aligning with prior reports of more aggressive disease in younger MM patients, who exhibit higher symptom severity.As more patients are onboarded and data collection continues through the MyMM app, this will enable more comprehensive analysis, including subgroup assessments by disease stage (Monoclonal Gammopathy of Unknown Significance, smouldering myeloma, multiple myeloma), further demonstrating potential of digital health tools for continuous monitoring and personalised disease management."

Clinical • Patient reported outcomes • Real-world • Real-world evidence • CNS Disorders • Constipation • Depression • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Monoclonal Gammopathy • Mood Disorders • Multiple Myeloma • Oncology • Pain • Psychiatry • Xerostomia

REAL-WORLD INFUSION OF INTRAVENOUS ISATUXIMAB IN 30-MINUTE FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA. EXPERIENCE OF 5 CENTERS IN SPAIN. (EHA 2025) - "This real-world study confirms that 30-minute isatuximab infusions are safe and well-tolerated. IRR at initial isatuximab treatment does not predict a IRR at rapid infusion. The shortened infusion time improves patient quality of life and optimizes healthcare resources."

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology

SUCCESSFUL EARLY RESCUE WITH ISATUXIMAB PLUS CARFILZOMIB-DEXAMETHASONE (ISA-KD) IN DARATUMUMAB-REFRACTORY NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS WITH "NO WASHOUT PERIOD". (EHA 2025) - "All of our patients with MM refractory to daratumumab achieved an objective, rapid and deep response after treatment with Isa-KD without having performed any washout period between daratumumab and isatuximab. Further real-word studies are needed in MM patients refractory to daratumumab and with few previous therapy lines, in whom combinations of Isatuximab might still be a suitable second therapy line without the need of changing the therapeutic target CD38 or expose them to newer drugs with a different mecanism of action and toxicity profile."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

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

ANALYSIS OF SUSTAINED MRD NEGATIVITY IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE WITH OR WITHOUT ISATUXIMAB (PHASE III ISKIA TRIAL) (EHA 2025) - P3 | "Isa-KRd pts received 4 full-dose Isa-KRd induction cycles, melphalan at 200 mg/m2 (MEL200) and ASCT, 4 full-dose Isa-KRd consolidation cycles, and, thereafter, 12 28-day light consolidation cycles [Isa 10 mg/kg IV on days (dd) 1, 15; K 56 mg/m2 IV dd 1; R 10 mg PO daily dd 1-21; d 20 mg PO dd 1, 15]. The addition of isatuximab to KRd induction-consolidation and the prolonged light consolidation significantly increased the rates of 10-6 sustMRD negativity in NDMM pts (including those with high-risk disease) and did not cause any additional safety issues."

Clinical • Minimal residual disease • P3 data • Cardiovascular • Infectious Disease • Multiple Myeloma • Neutropenia • Pulmonary Embolism • Respiratory Diseases • Thrombocytopenia

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 (EHA 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

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 (EHA 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

IMPACT OF 1Q GAIN AND AMPLIFICATION IN PATIENTS TREATED WITH ANTI-CD38 MONOCLONAL ANTIBODIES. REAL WORLD DATA FROM A SINGLE CENTER IN SPAIN. (EHA 2025) - "Daratumumab was mostly used in combination with carfilzomib (18.3%), bortezomib (17.4%), bortezomib and melphalan (15.7%) and lenalidomide (12.2%). Chromosome 1q alterations are frequently found associated with other high-risk features. In daratumumab-treated patients, a trend toward shorter PFS was observed but 1q alterations did not remain an independent risk factor in the multivariate analysis when adjusting for other high-risk cytogenetic alterations. 1q gain did not impact response rates or survival in patients treated with isatuximab."

Clinical • IO biomarker • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology

AUTOLOGOUS STEM CELL TRANSPLANT - DOES IT BENEFIT MULTIPLE MYELOMA PATIENTS IN ERA OF CD38 MONOCLONAL ANTIBODIES? (EHA 2025) - "TrinetX, a global federated research network that provides a dataset of electronic medical records from different healthcare organizations (HCOs) was utilized to query patients with MM, who had received QT with Isatuximab/Daratumumab, Lenalidomide, Bortezomib, Dexamethasone. Patients receiving ASCT were younger, and the majority were Caucasians. After matching for age, race and gender, it was seen that there is no difference in OS in both groups. Further prospective studies are required to compare the efficacy of ASCT in the era of QT."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation