Meletios Dimopoulos; ASH 2025: B-Cell Maturation Antigen Bispecific Antibody Linvoseltamab Brings High Response Rates in Patients with Relapsed/Refractory Multiple Myeloma

B-Cell Maturation Antigen Bispecific Antibody Linvoseltamab Brings High Response Rates in Patients with Relapsed/Refractory Multiple Myeloma

An interview with:

Meletios-Athanasios C. Dimopoulos MD, Professor and Chair, Department of Clinical Therapeutics (Alexandra Hospital), School of Medicine, University of Athens, Greece.

ORLANDO, USA—The bispecific monoclonal antibody linvoseltamab achieved high rates of clinical response when used in combination with anti-CD 38 therapy in patients who had relapsed/refractory multiple myeloma. Early findings on efficacy and safety from the phase 1b LINKER-MM2 trial were announced at the 2025 Annual Meeting of the American Society of Hematology by Meletios Dimopoulos MD, Chair of Clinical Therapeutics at the University of Athens in Greece. Peter Goodwin caught up with him just after his talk:

Audio Journal of Oncology: Meletios-Athanasios C. Dimopoulos MD

IN: [GOODWIN]I am here at the American….

OUT: ….. Journal of Oncology, I’m Peter Goodwin. 8:20 secs

2025 ASH Abstract 2254

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 ABSTRACT: 2254

Title :

“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”

Poster Abstract Session, Speaker: Meletios Dimopoulos, MD

Authors

Meletios Dimopoulos 1, Sosana Delimpasi2, Salomon Manier3, Jean-Marie Michot4, Enrique Ocio5, Samuel Rubinstein6, Joselle Cook7, Maria Del Carmen Martinez Chamorro8, Aurora Breazna9, Amishi Dhadwal9,Yogita Ghodke9, Sheila Masinde9, Glenn Kroog9, Shawn Sarkaria9, Albert Oriol10

Institutions:

1 Alexandra General Hospital, National and Kapodistrian University of Athens, Athens, Greece, 2Department of Hematology and Bone Marrow Transplantation Unit, General Hospital Evangelismos, Athens, Greece, 3 Hematology Department, Lille University Hospital, Lille, France, 4 Gustave Roussy Cancer Campus, Villejuif, France, 5 Servicio de Hematología y Hemoterapia, Hospital Universitario Marqués de Valdecilla University Hospital (IDIVAL) Universidad de Cantabria Santander, Santander, Spain, 6 Department of Hematology/Oncology, University of North Carolina, Chapel Hill, NC, United States, 7

Mayo Clinic, Rochester, MN, United States, 8 Hematology Department, Hospital Universitario Quirónsalud Madrid and Universidad Europea de Madrid, Madrid, Spain, 9 Regeneron Pharmaceuticals, Inc., Tarrytown, NY, United States, 10 Department of Hematology, Institut Català d’Oncologia i Institut Josep Carreras Hospital Germans Trias i Pujol, Badalona, Spain

Phase 1b LINKER-MM2 trial (NCT05137054).

Introduction

LINVO, a human B-cell maturation antigen (BCMA)xCD3 bispecific antibody, was recently approved for triple-class exposed (TCE) RRMM after ≥3 prior therapies (EU) or ≥4 prior lines of therapy (US), demonstrating high efficacy and a generally manageable safety profile. Combining LINVO with an anti-CD38 mAb, such as DARA or ISA, may provide additional benefit to pts with RRMM. Here we report pooled safety and efficacy results from the LINVO + DARA and LINVO + ISA cohorts during the dose-finding portion of the Phase 1b LINKER-MM2 trial (NCT05137054).

Methods

Eligible pts were aged ≥18 years with RRMM that progressed after ≥3 lines of therapy (LoTs), or ≥2 LoTs if TCE or double-class refractory (immunomodulatory drug [IMiD] + proteasome inhibitor [PI]). Prior treatment (tx) with DARA or ISA was allowed if previously tolerated and ≥6 months (mos) or ≥3 mos washout, respectively, had elapsed since last exposure. Tx began with LINVO monotherapy (Cycle [C]0; 28-day cycle) consisting of 2 step-up doses (5 mg, 25 mg) and 2 full doses (dose level [DL]1 100 mg; DL1b 150 mg; DL2 200 mg) before standard dosing of DARA or ISA was added at C1. LINVO was given once weekly in C1–3 and once every 2 weeks in C4+. At the end of 2024, dosing once every 4 weeks was implemented after C6 if a very good partial response or better (≥VGPR) was achieved. Dexamethasone premedication was required during the first 2 cycles and then given per label for DARA or ISA. Primary endpoints: dose-limiting toxicities (DLTs) and tx-emergent adverse events (TEAEs). Key secondary endpoints: overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and rate of minimal residual disease (MRD) negativity. The analyses reported here combine the LINVO + DARA and LINVO + ISA cohorts.

Results

As of May 7, 2025, 42 pts were enrolled. All pts were included in the safety analysis set: DL1 (DARA, n=12; ISA, n=6), DL1b (n=6; n=10), or DL2 (n=8; n=0); 37 were included in the efficacy analysis set: DL1 (DARA, n=11; ISA, n=5), DL1b (n=5; n=9), or DL2 (n=7; n=0). At baseline, all pts had received ≥1 PI (refractory to ≥1 PI: 76%) or ≥1 IMiD (refractory to ≥1 IMiD: 86%), and 21 pts (50%) had received prior DARA or ISA (refractory to DARA or ISA: 33% [DARA, n=4; ISA, n=10]). Median number of prior LoTs was 3 (range 2–8), including 50% of pts with TCE and 21% with triple-class refractory disease. Median age was 68 years (range 42–86); male, 57%; ISS stage III at study entry, 12%; high-risk cytogenetics, 31%; bone marrow plasma cells ≥50%, 31%; and soft tissue plasmacytomas, 33% (extramedullary, 12%). Median follow-up duration was 14.8 mos for DL1 (DARA 21.3; ISA 11.3), 7.6 mos for DL1b (DARA 13.5; ISA 5.2), and 5.9 mos for DL2 (all DARA), with 44%, 50%, and 63% of pts still receiving tx, respectively. The most common TEAEs were anemia (any grade [Gr] 48%; Gr 3/4 26%), neutropenia (41%; 41%), diarrhea (38%; 2%), and thrombocytopenia (38%; 17%). Cytokine release syndrome was reported in 33% of pts (all Gr 1/2 events except 1 Gr 3 event during the step-up period that fully resolved). No pts experienced immune effector cell-associated neurotoxicity syndrome (ICANS). Infections were reported in 32 pts (any Gr 76%; Gr ≥3 40%), and 3 resulted in death (1 tx related: cytomegalovirus [CMV] pneumonia; 2 tx unrelated: C. diff colitis and lower respiratory infection). One DLT was observed at DL1b in the ISA cohort (Gr 3 Epstein–Barr virus pharyngitis) and 1 was observed at DL2 in the DARA cohort (Gr 5 CMV pneumonia). Among efficacy evaluable pts, ORR was 75% at DL1 (12/16; ≥VGPR rate 75%), 93% at DL1b (13/14; ≥VGPR rate 57%), and 86% at DL2 (6/7; ≥VGPR rate 86%). Of 10 MRD-evaluable pts, all were MRD negative (<10−5by clonoSEQ or EuroFlow). The 12-mo DOR rate was 79% (95% confidence interval [CI] 52–92; median DOR not reached) and 12-mo PFS rate was 73% (95% CI 53–86; median PFS not reached). Pharmacokinetic analyses showed LINVO concentrations were not affected by the addition of DARA or ISA.

Conclusions:

In pts with heavily pretreated RRMM, half of whom had prior anti-CD38 mAb exposure, the combination of LINVO and DARA or ISA was feasible, inducing a high rate of deep and durable responses, and exhibiting a safety profile similar to that reported for each individual drug. These preliminary data support continued development of LINVO plus an anti-CD38 mAb for the tx of pts with MM.

ASH 2025 Audio Journal of Oncology: Meletios-Athanasios C. Dimopoulos. Posted January 21, 2026