Lynozyfic (linvoseltamab-gcpt) / Regeneron, Sanofi - LARVOL DELTA

Safety and efficacy of linvoseltamab as a simplified monotherapy first-line regimen in NDMM: Initial Results from the window of opportunity Phase 1/2 LINKER-MM4 trial (ASH 2025) - P1/2 | "In this larger, longer follow-up analysis, LINVO monotherapy continues to have high ORRand a generally manageable safety profile in NDMM, with no Gr ≥2 CRS events and 1 Gr 1 ICANS eventobserved. Responses may deepen over time, especially in the 200 mg cohort, supporting the furtherexploration of LINVO as a foundational drug in NDMM front-line regimens."

Clinical • Monotherapy • P1/2 data • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Plasmacytoma • Pneumonia • Respiratory Diseases

A phase 2 trial of abbreviated fixed-duration (Default 4 Cycles) linvoseltamab immuno-consolidation to deepen responses post newly diagnosed multiple myeloma combination therapy for minimal residual disease positivity (the IMMUNOPLANT Study) (ASH 2025) - P2 | "Although high-dose melphalan with autologous stem cell transplant (HDM-ASCT)remains an option for some patients, others prefer a harvest and delayed approach...Prophylaxis includestocilizumab 8 mg/kg to prevent cytokine release syndrome (CRS) 1 hour prior to first dose,dexamethasone 40/10mg C1 only, and standard anti-microbial prophylaxis, IViG, and thromboembolismprophylaxis...As of datacut-off, 14 patients completed 4 cycles of Linvo and underwent MRD assessment with 100% (95%CI: 76.8-100%) achieving MRD negativity by both NGS clonoSEQ (10-6) and flow cytometry (10-5) (13 sCR; 1 VGPR).All patients remain alive, with no relapses and all after C4 have initiated lenalidomide-based maintenancetherapy per treating physician... Recent randomized studies of quad-therapies have shown unprecedented MRD negativeresponses (e.g. PERSEUS, ADVANCE, MIDAS) and in turn, HDM-ASCT may not confer further benefit inthese patients. Given the recent clinical success of T cell..."

Combination therapy • Minimal residual disease • P2 data • Residual disease • Cardiovascular • Cough • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Respiratory Diseases

Patient-reported Quality of Life with Linvoseltamab in Triple-class Exposed Patients with Relapsed/refractory Multiple Myeloma: 2-year Results from the LINKER-MM1 Phase 1/2 Clinical Trial (IMS 2025) - "Improvements in pt-reported QoL, PF, pain, and fatigue were robust over 2 years of linvoseltamab treatment, complementing clinical benefits and supporting a favorable benefit–risk profile."

Clinical • HEOR • P1/2 data • Fatigue • Hematological Malignancies • Multiple Myeloma

LINKER-SMM2: A Study to Compare Linvoseltamab and Daratumumab Treatment in High-Risk Smoldering Multiple Myeloma (HR-SMM) (clinicaltrials.gov) - P3 | N=270 | Not yet recruiting | Sponsor: Regeneron Pharmaceuticals

New P3 trial • Hematological Malignancies • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma

Antibody-Drug Conjugates, T-Cell Engager Bispecific Antibodies and Chimeric Antigen Receptor T Cells for Multiple Myeloma: What's the Current Status? (PubMed, Target Oncol) - "This has resulted in European Medicines Agency and US Food and Drug Administration approval of agents targeting the B-cell maturation antigen: antibody-drug conjugate belantamab mafodotin (belantamab), bispecific T-cell engaging antibodies teclistamab, elranatamab and linvoseltamab, and chimeric antigen receptor T-cell products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). Talquetamab, a bispecific T-cell engaging antibody targeting G protein coupled receptor family C group 5 member D has also been approved by the European Medicines Agency and Food and Drug Administration. With increasing availability of these agents, knowledge on the efficacy and safety of these novel treatments will be essential for future multiple myeloma care. In this narrative review, we discuss the pivotal trials, current real-world evidence and recent insights in the mechanisms of resistance of antibody-drug conjugates, bispecific T-cell engaging antibodies and..."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Real-World Outcomes of Heavily Pretreated Relapsed Refractory Multiple Myeloma Patients Treated with Bispecific Antibodies (TCT-ASTCT-CIBMTR 2026) - "INTRODUCTION 4 Bispecific antibodies (BsAb): Teclistamab (Tec), Elranatamab (Elran), Talquetamab (Tal) & Linvoseltamab are approved for relapsed refractory multiple myeloma (RRMM) after ≥4 lines of therapy (LOT), with impressive overall response rates (ORR) and progression free survival (PFS). 3. To compare OS between early responders (those achieving partial response, VGPR, complete remission within ≤1 month of therapy initiation) and patients with stable or progressive disease at 2 month post bispecific antibody"

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

BCMA Bispecific Antibody Therapy for Post-BCMA CAR T-Cell Therapy Relapse (RECLAIM) (clinicaltrials.gov) - P2 | N=34 | Not yet recruiting | Sponsor: Medical College of Wisconsin | Initiation date: Dec 2025 ➔ Mar 2026

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and Efficacy of Linvoseltamab (LINVO) in Patients (Pts) with High-risk Smoldering Multiple Myeloma (HR-SMM): First Results from the Phase 2 LINKER-SMM1 Trial (IMS 2025) - P2 | "Tocilizumab was used in 2 pts. LINVO in HR-SMM was highly active with 100% ORR, and the safety profile appeared more favorable compared to RRMM. These data support further investigation of LINVO as an early intervention for SMM."

Clinical • P2 data • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Respiratory Diseases • Smoldering Multiple Myeloma

Linvoseltamab (LINVO) + bortezomib (BTZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): First results from the LINKER-MM2 trial. (ASCO 2025) - P1 | "Dexamethasone premedication was limited to C0–1...One DLT occurred at DL2 (Gr 3 CMV colitis on day 48; resolved with tx delay and ganciclovir)... LINVO + BTZ induced high response rates, with encouraging early DOR and PFS, in a population that was mostly PI-refractory. Safety was consistent with the known profile of each drug, and risk of Gr 3–5 infection was similar to LINVO monotherapy. These data will inform LINVO combination strategies for earlier LoT."

Clinical • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology • Pneumonia • Respiratory Diseases • Thrombocytopenia

LINKER-MM5: A Study to Compare Linvoseltamab Monotherapy and Linvoseltamab + Carfilzomib Combination Therapy With Standard-of-Care Combination Regimens in Adult Participants With Relapsed/Refractory Multiple Myeloma (RRMM) (clinicaltrials.gov) - P3 | N=915 | Recruiting | Sponsor: Regeneron Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Monotherapy • Hematological Malignancies • Multiple Myeloma • Oncology

Linvoseltamab (LINVO) + carfilzomib (CFZ) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the LINKER-MM2 trial. (ASCO 2025) - P1 | "Dexamethasone premedication was limited to C0–1. LINVO + CFZ induced a high rate of deep and durable responses with a safety profile consistent with the individual drugs, supporting further development. Enrollment at 200 mg LINVO in combination with CFZ is ongoing."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

LINVOSELTAMAB + CARFILZOMIB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL RESULTS FROM THE LINKER-MM2 TRIAL (EHA 2025) - P1 | "Dexamethasone premedication was limited to C0-1. LINVO + CFZ induced a high rate of deep and durable responses with a safety profile consistent with the individual drugs, supporting further development. Enrollment of patients receiving LINVO 200 mg in combination with CFZ is ongoing."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia

EARLY, DEEP, AND DURABLE RESPONSES, AND LOW RATES OF CRS WITH REGN5458, A BCMAXCD3 BISPECIFIC ANTIBODY, IN A PHASE 1/2 FIRST-IN-HUMAN STUDY IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (EHA 2022) - P1/2 | "Early, deep and durable responses were seen in triple- to penta-refractory pts with RRMM, with a 75.0% response rate at the combined 200–800 mg dose levels. The Phase 2 portion of the study is currently recruiting."

Clinical • P1/2 data • Fatigue • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology

LINKER-MM1 study: Linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma. (ASCO 2023) - P1/2 | "Linvoseltamab 200 mg showed better efficacy compared with 50 mg, including in pts with high disease burden. The 200 mg dose had consistent efficacy across high-risk subgroups and induced responses in pts who progressed on 50 mg. Safety was consistent across Ph 2 doses."

Clinical • Anemia • Fatigue • Hematological Disorders • Hematological Malignancies • Immune Modulation • Infectious Disease • Inflammation • Multiple Myeloma • Oncology • Plasmacytoma

Evaluation of the efficacy and safety of two different linvoseltamab Phase 2 dose regimens: Results from LINKER-MM1 (IMW 2023) - P1/2 | "Linvoseltamab 200 mg showed higher efficacy than 50 mg. Notably, high ORRs with 200 mg were seen across subgroups, even in high-risk and high tumor burden subgroups. Supporting the higher dose, some pts who progressed on 50 mg responded after dose escalating to 200 mg."

Clinical • P2 data • Anemia • Cough • Fatigue • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Musculoskeletal Pain • Neutropenia • Oncology • Plasmacytoma • Respiratory Diseases

Linvoseltamab, a B-cell maturation antigen-targeted T-cell-engaging bispecific antibody, induces deep and durable responses in patients with relapsed or refractory multiple myeloma including difficult-to-treat subgroups (AACR 2024) - P1/2 | "The frequency and severity of infections decreased after 6 months coincident with Q4W dosing.Conclusions Linvoseltamab induced high rates of deep and durable responses in patients with RRMM including those in high-risk subgroups. Linvoseltamab is associated with a generally predictable timing of CRS, and the Q4W response adapted schedule in patients with ≥VGPR may provide a substantial benefit for patient convenience and is associated with a reduced infection rate."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Indirect comparison of linvoseltamab versus teclistamab for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). (ASCO 2024) - "The results suggest potentially greater efficacy for linvoseltamab vs teclistamab for all outcomes, highlighting its potential as a highly effective treatment option for TCE RRMM."

Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Comparative effectiveness of linvoseltamab versus standard-of-care (SOC) treatment (tx) in real-world patients (pts) in the United States (US) with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). (ASCO 2024) - P1/2 | "Linvoseltamab significantly improved outcomes vs RW SOC in the US, highlighting its potential as a highly effective tx in pts with TCE RRMM."

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

LINVOSELTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA IN THE LINKER-MM1 STUDY: DEPTH AND DURABILITY OF RESPONSE AT 14-MONTH MEDIAN FOLLOW-UP (EHA 2024) - P1/2 | "Linvoseltamab induced high rates of deep and durable responses in patients with RRMM, including those inhigh-risk subgroups. Long-term data are critical to establish the value of linvoseltamab; 14-month medianfollow-up data, including durability across subgroups, will be presented at the meeting."

Clinical • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Plasmacytoma

Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma. (PubMed, J Clin Oncol) - "Linvoseltamab 200 mg induced deep and durable responses, with a median DOR of 29.4 months, in patients with RRMM with an acceptable safety profile."

Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Inflammation • Multiple Myeloma • Neutropenia • Oncology

Assessment of health-related quality of life (HRQoL) in triple-class–exposed patients with relapsed or refractory multiple myeloma (RRMM) treated with linvoseltamab in the LINKER-MM1 trial. (ASCO 2024) - P1/2 | "Over 76 weeks of treatment, improvements in measures of HRQoL including pain and fatigue were reported in patients with triple-class exposed RRMM receiving linvoseltamab; responders showed significant improvements on all scales. These PRO results support a favorable benefit–risk profile of linvoseltamab. Clinical trial information: NCT03761108."

Clinical • HEOR • Fatigue • Hematological Malignancies • Multiple Myeloma • Oncology • Pain

BCMA biology and therapeutic targeting in multiple myeloma: From ligand signaling to antigen escape. (PubMed, Semin Hematol) - "We then summarize the clinical development and distinguishing features of currently approved BCMA-targeted modalities-CAR T-cell therapies (ide-cel, cilta-cel), bispecific T-cell engagers (teclistamab, elranatamab, linvoseltamab), and the antibody-drug conjugate (belantamab mafodotin)-highlighting their efficacy, toxicity profiles, and practical positioning in relapsed/refractory MM. Finally, we review emerging resistance mechanisms, including γ-secretase-driven sBCMA elevation, ligand-rich APRIL/BAFF niches, and therapy-induced TNFRSF17 lesions, ranging from biallelic deletions to epitope-altering missense mutations and in-frame deletions within the BCMA extracellular domain. These insights inform rational strategies such as γ-secretase inhibition, dual-target CAR T-cells and bispecific T-cell engagers."

IO biomarker • Journal • Developmental Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • TNFRSF17

Mass Spectrometry Profiling of Therapeutic Antibodies in Multiple Myeloma: m/z Features and Concordance with Immunofixation Electrophoresis. (PubMed, Biomedicines) - "The m/z library enabled attribution of interference to linvoseltamab (n = 9), daratumumab (n = 6), and teclistamab (n = 3); in 16 patients treated with other bispecifics, no drug-related peaks were detected after 3 months. Longitudinal analysis discriminated therapeutic from endogenous immunoglobulins, identified baseline M-protein, and prevented false residual signals. MS (EXENT®)-based characterization of t-mAbs improves response monitoring accuracy in multiple myeloma and supports integration of MS into routine laboratory practice."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Current landscape and future prospects of bispecific antibodies in multiple myeloma. (PubMed, J Egypt Natl Canc Inst) - "The recent FDA approvals of teclistamab, talquetamab, elranatamab and linvoseltamab have reshaped the therapeutic landscape of relapsed/refractory MM (RRMM), achieving overall response rates (ORR) exceeding 60% in heavily pretreated patients...In addition to these milestones, early-phase data from emerging trispecific antibodies, such as ISB 2001, show ORRs as high as 75% and deep responses, including stringent complete responses (sCR) and minimal residual disease (MRD) negativity...We synthesize the latest clinical trial data, explore strategies for overcoming resistance, and discuss ongoing efforts to optimize combination regimens and sequencing. By critically evaluating these advancements, we highlight the evolving role of BsAbs and trispecific antibodies in redefining treatment paradigms, with the ultimate goal of improving patient outcomes and advancing toward a potential cure for multiple myeloma."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Incidence of second primary malignancies (SPMs) following bispecific antibody (BsAb) therapy for lymphoid malignancies: A descriptive analysis of clinical trials (ASH 2025) - "Included agents were blinatumomab (CD19×CD3), glofitamab, mosunetuzumab, epcoritamab, and odronextamab (all CD20×CD3), as well as elranatamab, teclistamab, and linvoseltamab (BCMA×CD3), and talquetamab (GPRC5DxCD3). Notably, some reported cases may represent disease progression rather than true SPMs. However, limited follow-up duration across trials warrants continued long-term surveillance, particularly as agents move to frontline settings where longer survival may reveal delayed malignancies."

Clinical • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lung Cancer • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • CD20