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

Hematotoxicity and immune deficits with bispecific antibodies: A systematic review and meta-analysis in lymphoma and multiple myeloma (ASH 2025) - "Among NHL cohorts, the BsAb distribution was: 7 glofitamab, 6 mosunetuzumab, 5 epcoritamab, and 4 odronextamab. Among MM cohorts, 6 received teclistamab, 3 talquetamab, 1 teclistamab and talquetamab, 2 elranatamab, 2 linvoseltamab and 1 etentamig (ABBV-383)... Cytopenias affect a substantial proportion of patients treated with BsAbs, particularly in MM and in NHL with combination regimes. These findings support the need for systematic hematologic monitoring, IG surveillance and tailored pre-emptive strategies to mitigate infection risk.This study represents the first and most comprehensive meta-analysis of hematotoxicity and immune deficits with BsAbs, establishing a benchmark across clinical settings."

Retrospective data • Review • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia

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

A novel and highly effective truncated BCMA safety switch for adoptive cell therapy (ASH 2025) - "We selected BCMA as a safety switch as i) it is not naturally expressed on immune cells commonly used for adoptive cell therapies including T cells, NK cell, NKT cells, gd T cells, and macrophages, ii) its expression is restricted to plasma cells and a small subset of B cells amongst normal human tissues, and iii) highly effective BCMA-targeting bispecific T-cell engagers, such as teclistamab, elranatamab, and linvoseltamab are readily available in the clinic and used for the treatment of multiple myeloma...To assess the efficacy of the safety switch, CD19 CAR T cells co-expressing either ctBCMA or GPI-BCMA were transduced with GFP and cocultured with a B-cell lymphoma cell line at an effector to target ratio of 1:1 in the absence or presence of teclistamab, elranatamab or belantamab mafodotin or their respective isotype antibody controls...Conclusion In conclusion, our results indicate that either ctBCMA or GPI-BCMA may serve as a novel and highly effective safety..."

Clinical • IO biomarker • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • CD52 • CD55 • GPI • PD-L1

Efficacy of tocilizumab prophylaxis in preventing cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome: A systematic review and meta-analysis (ASH 2025) - "The Bispecific antibodies used were Teclistamab. Eltranatamab, Talquetamab, and Linvoseltamab... Tocilizumab is a viable option for preventing all grades of CRS and ICANS following CAR-T cell therapy and Bispecific antibodies. Randomized trials with larger patient populations are needed to further demonstrate its efficacy, safety, and the impact on treatment responses."

Cytokine release syndrome • Retrospective data • Review • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Infectious Disease • Inflammation • Leukemia • Lymphoma • Mantle Cell Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia

Validation of the high-risk consensus genomic staging system in the era of bispecific antibodies: Role of NGS and cytogenetic reclassification (ASH 2025) - "The median age at treatment initiation was 61 years (IQR 55–68), and 56.1% were male.Bispecific antibodies administered included teclistamab (27.6%), linvoseltamab (22.4%), talquetamab(21.4%), etentamig (14.3%), and elranatamab (12.2%).The most frequent high-risk cytogenetic alteration was 1q gain (38.8%), followed by del(17p) (21.4%),monoallelic del(1p32) (14.3%), t(4; 14) (11.2%), and t(14; 16) (3.1%). The revised IMWG-IMS high-risk genomic classification improved risk stratification over classic criteria ina large cohort of patients treated with bispecific antibodies. Even among heavily pretreated high-riskpatients, the updated classification more accurately identified those with poorer outcomes. Thesefindings support incorporating next-generation sequencing and refined cytogenetic definitions forprognostic assessment and treatment decisions in this patient population."

Next-generation sequencing • Hematological Malignancies • Multiple Myeloma • SDC1 • TP53

Health care resource utilization in patients with multiple myeloma receiving bispecific antibody therapy with teclistamab: A Medicare claims database analysis in the US (ASH 2025) - "Background :Four bispecific antibodies (bsAbs), teclistamab, elranatamab, talquetamab, and linvoseltamab have beenapproved for use in the U.S. in patients (pts) with relapsed/refractory (R/R) multiple myeloma (MM). Most pts with MM receiving teclistamab initiate treatment in an IP setting, with hospital LOS consistentwith dosing guidance from the prescribing information. A substantial proportion of those who initiateteclistamab in an OP setting are hospitalized within 30 days. Treatment duration and percentage of ptscompleting SUD were consistent with values in other real-world studies of teclistamab."

Claims database • Clinical • HEOR • Medicare • Reimbursement • US reimbursement • Hematological Malignancies • Multiple Myeloma

Real-world safety and efficacy of BCMA bispecific antibodies in relapsed light chain amyloidosis (ASH 2025) - "The current standard of care for newly diagnosed AL Amyloidosis isDaratumumab, Cyclophosphamide, Bortezomib and Dexamethasone with a hCR rate of 59.5% withmedian time to hCR of 67.5 days. There are three FDA approved B-cell maturation antigen (BCMA)bispecific antibodies (BSAbs) for the treatment of relapsed refractory multiple myeloma (RRMM) after 4+lines of therapy, Teclistimab, Elranatamab and Linvoseltamab... Of the 20 patients, median age 73 (60-83), 55% were female and the majority were caucasian 17(85%). Patients received a median of 4 (3-10) prior lines of treatment. There were 14 patients with cardiacinvolvement with the following breakdown based on the 2004 Mayo Cardiac Staging: 3 with stage IIIB, 9with stage IIIA, none with stage II and 2 with stage I. The average NTproBNP at the time of BCMA BsAbinitiation was 8828 with a minimum of 284 and maximum of 70,000."

Clinical • Real-world • Real-world evidence • Amyloidosis • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Respiratory Diseases

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

Factors influencing patient treatment selection among bispecific antibodies for relapsed/refractory multiple myeloma (RRMM): A mixed methods study (ASH 2025) - "The attributes and levelswere informed by clinical data available for elranatamab, linvoseltamab, talquetamab, and teclistamab.Finally, patients were asked to select the single most and single least meaningful attribute per categorybased on the difference in highest and lowest levels, reflecting their overall prioritization. The findingshighlight the need for a large-scale quantitative study to more systematically assess patient preferencesand quantify the trade-offs that patients are willing to make among key attributes in treatment selection.The results of this study will directly inform the design and selection of attributes for a discrete choiceexperiment (DCE). Based on the findings, a patient DCE focusing on BsAbs for treatment of RRMM shouldinclude attributes related to mode of administration, dosing schedule, survival, response rate, seriousside effects like ICANS and grade 3-4 infections, and quality of life-related side effects, such as loss oftaste and..."

Clinical • Hematological Malignancies • Infectious Disease • Multiple Myeloma

Safety and efficacy of linvoseltamab (LINVO) combined with anti-CD38 monoclonal antibodies (mAbs) daratumumab (DARA) or isatuximab (ISA) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial results from the multicohort, Phase 1b LINKER-MM2 trial (ASH 2025) - P1 | "Dexamethasonepremedication was required during the first 2 cycles and then given per label for DARA or ISA. Pharmacokineticanalyses showed LINVO concentrations were not affected by the addition of DARA or ISA.ConclusionsIn pts with heavily pretreated RRMM, half of whom had prior anti-CD38 mAb exposure, the combinationof LINVO and DARA or ISA was feasible, inducing a high rate of deep and durable responses, andexhibiting a safety profile similar to that reported for each individual drug. These preliminary datasupport continued development of LINVO plus an anti-CD38 mAb for the tx of pts with MM."

Clinical • P1 data • Cytomegalovirus Infection • Epstein-Barr Virus Infections • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • 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

Lynozyfic: “ Linvoseltamab maintained a generally manageable safety profile at 21.3 months of median follow up, including decreased infection risk over time and no new safety signals“; Multiple myeloma (Regeneron Pharmaceuticals) - Regeneron Roundtable: Lynozyfic

P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Linvoseltamab in multiple myeloma: a BCMA × CD3 bispecific antibody for relapsed and refractory disease. (PubMed, Ann Med Surg (Lond)) - No abstract available

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Lynozyfic: "Deep responses: ≥70% VGPR or better across all dose levels despite limited follow up; responses deepening over time which is expected to continue"; Multiple myeloma (Regeneron Pharmaceuticals) - Regeneron Roundtable: Lynozyfic: "MRD Negativity: across dose groups, 95% (19/20) patients who achieved ≥VGPR and had evaluable samples were MRD negative at 10−5 sensitivity"

P1/2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Lynozyfic: ’Initial data from LINKER-SMM1 in high-risk smoldering multiple myeloma patients demonstrated nearly 40% ≥CR at less than 4 months of follow up“; Multiple myeloma (Regeneron Pharmaceuticals) - Regeneron Roundtable: Lynozyfic

P2 data • Hematological Malignancies • Multiple Myeloma • Oncology

Lynozyfic: Initiation of P3 LINKER-SMM2 trial for high-risk smoldering myeloma in H1 2026 (Regeneron Pharmaceuticals) - Regeneron Roundtable Lynozyfic: PFS data from P3 LINKER-SMM2 trial for high-risk smoldering myeloma in 2030

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

Lynozyfic: "Significant market opportunity in multiple myeloma" (Regeneron Pharmaceuticals) - Regeneron Roundtable: Lynozyfic: "Lynozyfic has the potential to become a significant portion of the $30B+ multiple myeloma market by advancing through lines of therapy"

Commercial • Hematological Malignancies • Multiple Myeloma • Oncology

Lynozyfic: MRD negativity and PFS data from P3 LINKER-MM3 trial (NCT05730036) for 3L+ r/r multiple myeloma in 2027 (Regeneron Pharmaceuticals) - Regeneron Roundtable Lynozyfic: MRD negativity data from P3 LINKER-MM6 trial for 1L multiple myeloma in 2028; PFS data from P3 LINKER-MM6 trial for 1L multiple myeloma in 2030

P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Lynozyfic: Initiation of P3 LINKER-MM7 trial for 1L multiple myeloma in H1 2026 (Regeneron Pharmaceuticals) - Regeneron Roundtable Lynozyfic: MRD negativity data from P3 LINKER-MM7 trial for 1L multiple myeloma in 2028; PFS data from P3 LINKER-MM7 trial for 1L multiple myeloma in 2030; Initiation of P2/3 LINKER-MM8 trial for 1L multiple myeloma in H1 2026; MRD negativity data from P3 LINKER-MM7 trial for 1L multiple myeloma in 2030; PFS data from P2/3 LINKER-MM8 trial for 1L multiple myeloma in 2032

New P2/3 trial • New P3 trial • P2/3 data • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Lynozyfic: Initiation of P3 LINKER-MM5 trial (NCT07222761) for r/r multiple myeloma in Q1 2026 (Regeneron Pharmaceuticals) - Regeneron Roundtable Lynozyfic: Data from P3 LINKER-MM5 trial for r/r multiple myeloma in 2028

Trial initiation date • Hematological Malignancies • Multiple Myeloma • Oncology

Safety and Efficacy of Anti-B-cell Maturation Antigen (Anti-BCMA) Bispecific Antibodies for Relapsed/Refractory Multiple Myeloma: A Systematic Review of Clinical Trials. (PubMed, Cureus) - "AMG-420, AMG-701, elranatamab, REGN5458, teclistamab (Tec), alnuctamab (ALNUC), and ABBV-383 are the seven anti-BCMA-CD3 bispecific Abs currently being assessed in clinical trials as monotherapy and in combination with immunomodulators/proteasome inhibitors against RRMM. Our analysis of the trials revealed that bispecific Abs showed efficacy in RRMM, with CRS and hematologic toxicities being the most common adverse events, mostly low-grade and manageable. Based on the promising efficacy and safety of BCMA targeting bispecific Abs, these drugs are emerging as a new therapeutic option for patients with advanced and RRMM."

Journal • Review • Hematological Disorders • Hematological Malignancies • Inflammation • Multiple Myeloma • Oncology

CAR T-cell therapy and bispecific antibodies in the management of multiple myeloma. (PubMed, Hematology Am Soc Hematol Educ Program) - "At present, two B-cell maturation antigen (BCMA)-targeted CAR T-cell therapies, idecabtagene vicleucel and ciltacabtagene autoleucel, are approved for standard use in the United States. There are currently 4 commercially approved bispecific antibodies: teclistamab, elranatamab, and linvoseltamab, which target BCMA, as well as talquetamab, which targets the GPRC5D antigen on the surface of plasma cells. In this review, we explore (a) the advantages and challenges of integrating CAR T-cell therapy earlier in the RRMM treatment course; (b) the safety and efficacy of bispecific antibodies and their evolving role in the current RRMM treatment paradigm; (c) practical considerations for both modalities, focusing on patient selection and supportive care strategies; and (d) recommendations for sequencing of T-cell redirecting therapies to maximize long-term outcomes."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Endless possibilities and how to exploit them? What is the optimal treatment sequence? (PubMed, Hematology Am Soc Hematol Educ Program) - "For transplant-eligible, transplant-deferred, and fit transplant-ineligible patients who are younger than 80 years old, we use anti-CD38 mAb-, lenalidomide-, and bortezomib/carfilzomib-based quadruplets as an induction regimen. For early relapse (1-3 prior lines), chimeric antigen receptor T-cell therapies targeting B-cell maturation antigen (BCMA) have demonstrated superiority over standard regimens, with ciltacabtagene autoleucel (cilta-cel) being the most efficacious product currently, albeit with some unique toxicities such as parkinsomism...In late relapse (≥4 prior lines), bispecific antibodies (BsAbs) targeting BCMA (teclistamab, elranatamab, and linvoseltamab) and GPRC5D (talquetamab) have demonstrated impressive single-agent activity with distinct toxicity profiles...For patients with BCMA- and GPRC5D-refractory disease, FcRH5-targeting BsAb (cevostamab), BCL2 inhibitors for t(11;14)-positive disease, and novel trispecific antibodies (BCMAXCD38; BCMAXGPRC5D)..."

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

Regeneron Pharmaceuticals…announced encouraging data from the Phase 1/2 LINKER-MM4 trial evaluating Lynozyfic (linvoseltamab) in adults with newly diagnosed multiple myeloma (NDMM) who were transplant eligible or ineligible were shared in an oral presentation at the American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Across all dose levels (n=45), there was a 1.2 months median time to onset of response (range: 1-4.5 months). All three dose groups (50 mg, 100 mg and 200 mg) showed impressive efficacy, with a VGPR+ (very good partial response or better) of ≥70% with limited follow-up. Evidence shows that these responses are expected to deepen over time. Across all dose groups, 95% (19 of 20 patients) of all minimum residual disease (MRD) evaluable VGPR+ patients achieved MRD negative status at 10-5 sensitivity."

P1/2 data • Multiple Myeloma

EMN39: A Study to Learn How Safe and How Well Linvoseltamab Works Compared to Standard Treatment in Adult Patients With Multiple Myeloma Who Are Not Eligible for Transplant (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: European Myeloma Network B.V. | Not yet recruiting ➔ Recruiting

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