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

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

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Future on Bispecifics and Antibody-Drug Conjugates (SOHO 2025) - "The pivotal phase 1/2 MajesTEC-1 trial and the MagnetisMM trials led to the US Food and Drug Administration (FDA) approval of teclistamab and elranatamab, respectively, both of which target surface B-cell maturation antigen (BCMA) on MM cells. A third approved BsAb, talquetamab, has efficacy against another antigen, G protein-coupled receptor family C group 5 member D (GPRC5D), as evidenced in the MonumenTAL-1 trial...These include BCMA-targeting linvoseltamab as well as ABBV-383, which features a distinct bivalent BCMA-binding domain and a low-affinity CD3-binding domain in a unique 2+1 design. A third MM antigen, Fc receptor-like 5 (FcRH5), is targetable by the BsAb cevostamab. Several other BsAbs engage CD38, the target of daratumumab and isatuximab...The ongoing phase 3 MajesTEC-7 study is assessing the combination of teclistamab, daratumumab, and lenalidomide versus daratumumab, lenalidomide, and dexamethasone for newly diagnosed patients who are ineligible for, or..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • GZMB • SDC1 • SLAMF7

Current and future role of carfilzomib-based quadruplet combinations as therapy for newly diagnosed multiple myeloma. (PubMed, Hemasphere) - "The treatment of newly diagnosed multiple myeloma (NDMM) has advanced rapidly in recent years, with the standard of care (SOC) now including not only triplet combinations of proteasome inhibitors (PIs), immunomodulatory agents, and steroids but also quadruplet combinations that add the anti-CD38 monoclonal antibodies isatuximab (Isa) or daratumumab (D) to a triplet backbone. In addition to the widely used bortezomib-lenalidomide-dexamethasone (VRd) combination, an alternative triplet option that can be considered is the combination of the second-generation PI carfilzomib (K) with lenalidomide-dexamethasone (KRd)...KRd-based combinations may represent a suitable alternative to VRd for some patients. This article discusses measures that may help to establish KRd-based quadruplets as an additional SOC in this setting, including proper patient selection, steps to mitigate safety concerns, and the establishment of optimal dosing schedules."

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

Efficacy and Safety of Quadruplet Versus Triplet Regimens in Transplant-Ineligible Newly Diagnosed Multiple Myeloma: A Systematic Review, Meta-Analysis, and Network Meta-Analysis (SOHO 2025) - "In the NMA, D-VRd (daratumumab plus VRd [bortezomib, lenalidomide, dexamethasone]) was associated with the best PFS (P-score = 0.8637), followed by Isa-VRd (isatuximab plus VRd; P-score = 0.8050), DRd (P-score = 0.5737), VRd (P-score = 0.2564), and Rd (lenalidomide, dexamethasone; P-score = 0.0011). Quadruplet regimens significantly improve PFS, sCR, and MRD negativity in TIE-NDMM. D-VRd and Isa-VRD are comparable to DRd in terms of PFS based on indirect evidence. Large-scale randomized controlled trials are required to directly compare quadruplet regimens with DRd."

Retrospective data • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Daratumumab-Bortezomib-Lenalidomide-Dexamethasone vs Contemporary Treatment Alternatives in Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma: Results of a Systematic Literature Review and Network Meta-Analysis (SOHO 2025) - "For PFS, the Bayesian probability of DVRd having superior efficacy was 72% vs isatuximab-bortezomib-lenalidomide-dexamethasone (IsaVRd), 88% vs daratumumab-lenalidomide-dexamethasone (DRd), 91% vs daratumumab-bortezomib-melphalan-prednisone (DVMP), and 100% vs bortezomib-lenalidomide-dexamethasone (VRd). Of the currently available treatment options for TIE patients with NDMM, DVRd was associated with the highest probability of offering the best PFS and OS outcomes. These comparative efficacy data may help inform treatment selection for maximum benefit in TIE patients with NDMM. Acknowledgments: This study was funded by Johnson & Johnson."

Retrospective data • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Health-related quality of life (HRQoL) in frail patients with newly diagnosed multiple myeloma (NDMM) treated with isatuximab (Isa), bortezomib, lenalidomide, and dexamethasone (Isa-VRd) vs VRd alone (IMS 2025) - No abstract available

Clinical • HEOR • Hematological Malignancies • Multiple Myeloma

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

A network meta-analysis of randomized clinical trials in lenalidomide-exposed or -refractory multiple myeloma patients. (PubMed, ESMO Open) - "Emerging therapies, including chimeric antigen receptor T-cell (CAR-T-cell) therapy and bispecific antibodies, are set to reshape RRMM treatment paradigms. Trials such as CARTITUDE-4 and MajesTEC-3 are exploring these agents in earlier treatment lines, particularly for lenalidomide- and daratumumab-refractory patients. Our analysis provides an evidence-based hierarchy of lenalidomide-free regimens, supporting BVd as a preferred second-line treatment. Future studies should refine treatment sequencing strategies and evaluate novel agents in earlier disease stages to optimize outcomes for RRMM patients."

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

Cost of Anti-CD38 Monoclonal Antibodies in Combination With Bortezomib, Lenalidomide and Dexamethasone for the Frontline Treatment of Transplant-Ineligible Patients With Newly Diagnosed Multiple Myeloma in the US. (PubMed, J Health Econ Outcomes Res) - "Background: The efficacy of the combination of bortezomib, lenalidomide, and dexamethasone with daratumumab (DVRd) or isatuximab (IsaVRd) for the frontline treatment of transplant-ineligible (TIE) newly diagnosed multiple myeloma (NDMM) has been demonstrated in clinical trials. DVRd results in time savings vs IsaVRd, which is preferable for patients and caregivers. DVRd is a timesaving and less expensive frontline treatment option for patients with TIE NDMM than IsaVRd in the first and second year of treatment."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Single-cell immune landscape associated with Isatuximab, Carfilzomib, Lenalidomide, and Dexamethasone induction efficacy in Newly Diagnosed Myeloma (IMS 2025) - No abstract available

Clinical • Hematological Malignancies • Multiple Myeloma

DREAMM-7 Study of Belantamab Mafodotin + Bortezomib + Dexamethasone vs Daratumumab + Bortezomib + Dexamethasone in Relapsed/ Refractory Multiple Myeloma: Efficacy in Patients by Subsequent Therapy (SOHO 2025) - P3 | "Subsequent anti-CD38 mAbs were given in the third line and beyond (3L+); the most common regimens included isatuximab + pomalidomide + dexamethasone (n = 12); daratumumab monotherapy (n = 8); daratumumab + lenalidomide + dexamethasone (n = 6); and daratumumab + pomalidomide + dexamethasone (n = 6). In patients who received anti-CD38 mAbs, pomalidomide, or carfilzomib as the first subsequent therapy after BVd, the median time from the start of subsequent therapy to progression/death was ≈15 months, showing that subsequent therapy with these agents in the 3L + was effective post BVd and comparable to median PFS of DVd in the 2L+. Funded by GSK. Drug-linker technology licensed from Seagen Inc.; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

SKylaRk: KRDI in Transplant-Eligible MM (clinicaltrials.gov) - P2 | N=50 | Active, not recruiting | Sponsor: Massachusetts General Hospital | Trial completion date: Mar 2025 ➔ Mar 2026

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

Autologous NK Cell Therapy as a Consolidative Strategy after Auto-SCT (ICBMT 2025) - "Building on these findings, a randomized phase II clinical trial was initiated, comparing CellProtect in combination with the anti -CD38 antibody isatuximab versus isatuximab alone. Together, these strategies will define the next generation of NK cell immunotherapies. By integrating clinical translation with advanced genetic engineering and precision delivery platforms, the Alici group aims to broaden the therapeutic impact of NK cell s in multiple myeloma and extend their application to other hematologic and solid malignancies."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Solid Tumor • GZMB • PTPRC

Comparison of isatuximab-pomalidomide-dexamethasone versus elotuzumab-pomalidomide-dexamethasone in relapsed/refractory multiple myeloma patients: a target trial emulation using real-world data. (PubMed, Haematologica) - No abstract available

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

Consensus Guidelines and Recommendations for the anti-CD38-based Therapy in Clinical Practice for Relapsed/Refractory Multiple Myeloma: From the Pan-Pacific Multiple Myeloma Working Group. (PubMed, Clin Hematol Int) - "Anti-CD38 monoclonal antibodies (mAbs), including daratumumab and isatuximab, have become key components of treatment for relapsed/refractory multiple myeloma (RRMM). Moreover, anti-CD38 mAbs are recognized as key components within evolving treatment paradigms, supporting their use for combination strategies involving emerging immunotherapies such as CAR-T cells and bispecific antibodies. This consensus provides a framework to guide individualized treatment decisions and highlights the need for continued research to optimize the integration of anti-CD38 mAbs into the modern therapeutic landscape of RRMM."

IO biomarker • Journal • Review • Geriatric Disorders • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology

Ex Vivo Testing Platform Unveils Differential Response to Daratumumab and Isatuximab in Multiple Myeloma (SOHO 2025) - "The results of this study highlight the potential of PMAs to comprehensively evaluate the performance of therapeutic antibodies, even those designed for the same target. Such actionable insights may serve as a powerful tool for enabling greater personalization in therapy selection. Moreover, our investigation of the responses to daratumumab vs isatuximab indicates that these therapeutic antibodies are not always interchangeable, and their side-by-side evaluation merits further clinical investigation."

Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

FOXM1 down-regulation is a trigger of isatuximab-induced direct cell death in multiple myeloma cells with 1q. (PubMed, Haematologica) - "Not available."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • FOXM1

Comparative Efficacy and Safety of BCMA-Targeted CAR T-Cell Therapies and Bispecific Antibodies in Relapsed/Refractory Multiple Myeloma: A Comprehensive Review of Clinical Outcomes and Adverse Events (SOHO 2025) - " The monoclonal anti-CD38 antibodies daratumumab and isatuximab, when added to standard regimens, achieved ORRs of 60– 90%, median PFS of 11-22 months, and CR rates up to 40%, with infusion reactions (15-50%), neutropenia (20-40%), and infections representing the most common adverse events. The anti-BCMA ADC belantamab mafodotin yielded an ORR of approximately 32% in heavily pretreated cohorts, with a median DOR of 11 months, although ocular keratopathy (>60%) and thrombocytopenia (35– 45%) necessitated rigorous monitoring. BCMA × CD3 BiTEs such as teclistamab demonstrated ORRs of 60-65% and CR rates of 20– 30%, with cytokine release syndrome in 55-70% (predominantly grade 1-2), alongside frequent neutropenia (70%) and hypogammaglobulinemia. Targeted immunotherapies have shown strong response rates and lasting remissions in patients with relapsed or refractory multiple myeloma; however, their unique benefits and side effects highlight the need for personalized..."

Adverse events • CAR T-Cell Therapy • Clinical • Clinical data • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Long-Term Effectiveness and Safety of Isatuximab in Combination with Pomalidomide and Dexamethasone in a Japanese Patient with Refractory Multiple Myeloma and 1q21 Amplification: A Case Report. (PubMed, Case Rep Oncol) - "The only serious adverse event was grade 3 cataracts. Our case shows that isatuximab-Pd is capable of inducing an enduring response in a patient with 1q21+ RRMM."

Journal • Cataract • Hematological Malignancies • Multiple Myeloma • Oncology • Ophthalmology

Efficacy of Isatuximab plus Dexamethasone versus non Isatuximab-based Treatments in Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis (ESMO 2025) - No abstract available

Retrospective data • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Efficacy of Isatuximab Plus Dexamethasone Versus No Isatuximab-Based Treatments in Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis (SOHO 2025) - "Isatuximab-based regimens offer a clear clinical benefit in delaying treatment progression for RRMM patients, although OS improvement remains uncertain. Adverse events, particularly infusion reactions and URTIs, were increased and should be monitored closely. These findings support the clinical integration of isatuximab, but more long-term studies need to be done, taking patient characteristics into account to better define its survival benefit and long-term safety profile."

Retrospective data • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Sarclisa: “Extension of indication to include, in combination with bortezomib, lenalidomide and dexamethasone, the induction treatment of adult patients with newly diagnosed multiple myeloma…based on the results from study IIT15403 (GMMG-HD7)…. as a consequence, sections 4.1, 4.2, 4.4, 4.8, 5.1 and 5.2 of the SmPC are updated.” (European Medicines Agency) - CHMP Final Minutes of the meeting on 24 - 27 Mar 2025: “The committee adopted a request for supplementary information with a specific timetable”

CHMP • Hematological Malignancies • Multiple Myeloma • Oncology

The Impact of Anti-CD38 Monoclonal Antibody Therapy on Stem-Cell Mobilization Yields in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Referred from Community and Academic Oncology Practices: Single Center, Real World Data 2021-2024. (PubMed, Transplant Cell Ther) - "CD38 mAb-containing induction regimens were associated with inferior stem cell mobilization yields and higher resource utilization. Extended washout periods modestly improved yield, highlighting a potential modifiable factor. These findings support the need for tailored mobilization strategies in CD38 mAb-exposed patients and warrant prospective evaluation of alternative mobilization agents and collection protocols to optimize efficiency and cost-effectiveness in the ASCT setting."

Journal • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation • CD34

MODIFY: Isatuximab and Iberdomide as Immunotherapy for High Risk in Smouldering Myeloma (clinicaltrials.gov) - P2 | N=63 | Recruiting | Sponsor: University College, London | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2030 ➔ Nov 2032 | Trial primary completion date: Sep 2029 ➔ Nov 2032

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