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IMS
— Bispecific antibody yields 100% overall response rate in early data from phase II trial
by Mike Bassett, Staff Writer, MedPage Today
September 20, 2025 • 3 min read
TORONTO — Linvoseltamab (Lynozyfic) appeared effective in patients with high-risk smoldering multiple myeloma (HR-SMM), according to preliminary phase II trial data.
With a median follow-up of 3.9 months among 19 evaluable patients who received at least one full dose of linvoseltamab, the overall response rate (ORR) was 100%, with a very good partial response (≥VGPR) rate of 73.7%, and a complete or stringent complete response (≥CR) rate of 36.8%, reported Paula Rodríguez-Otero, MD, of the Cancer Center Clinica Universidad de Navarra in Pamplona, Spain.
Furthermore, in a subset of six patients who were included in a safety run-in (part 1 of the LINKER-SMM1 study), the ORR was 100%, ≥VGPR was 100%, and ≥CR was 83.3%, with a longer follow-up of 12.7 months.
The median time to first response was 1.7 months, and all responses were ongoing at the time of data cutoff, she reported at the International Myeloma Society annual meeting.
Linvoseltamab is a fully human BCMA×CD3 bispecific antibody that has demonstrated efficacy in relapsed/refractory myeloma (RRMM), and the agent’s safety profile in HR-SMM seemed more favorable than what has been seen in RRMM, Rodríguez-Otero said. Linvoseltamab 200 mg is FDA approved for triple-class exposed RRMM after ≥4 lines of therapy, based on phase I/II LINKER-MM1 data.
“We believe the data from this ongoing study, although it is still very preliminary, provides compelling evidence supporting linvoseltamab as a promising early intervention strategy with high-risk smoldering multiple myeloma that may eventually delay or prevent progression to active disease,” Rodríguez-Otero said.
She noted that previous phase III clinical trials have studied the impact of early intervention versus observation in patients with mostly HR-SMM and shown significant survival benefits.
Among the 80 treated patients in LINKER-MM1, the ORR was 71%, with a ≥VGPR of 63% and ≥CR of 52%. Median PFS was not reached after a median follow-up of 21.3 months. Minimal residual disease negativity (10-5 threshold) was achieved in 94% of evaluable patients with a ≥CR.
“So the hypothesis is that by intervening early in this stage of [HR-SMM], when the immune system is more functional than in the active disease, we may be able to either significantly delay, or even completely prevent, the progression from high-risk smoldering to active disease,” Rodríguez-Otero said.
LINKER-SMM1 is an open-label study of linvoseltamab monotherapy in treatment-naïve adults with a HR-SMM diagnosis within 5 years of study entry. Treatment began with a 3-week step-up schedule of 1 mg in week 1, 4 mg in week 2, and 24 mg in week 3, followed by linvoseltamab 200 mg in 28 day cycles.
As of May 2025, a total of 24 patients were enrolled in the study, all of whom are still receiving treatment.
The median age of the patients at baseline was 63 (n=10 age ≥65; n=3 age ≥75), and most (92%) patients had an ECOG performance stat of 0.
Regarding safety, while 22 patients (92%) had any grade treatment-emergent adverse events (TEAEs), just nine (38%) had a grade ≥3 TEAE.
There have yet to be any treatment discontinuations due to TEAEs, and there have been no deaths in the study, Rodríguez-Otero stated.
Neutropenia was the only grade ≥3 hematologic toxicity, occurring in six patients, while cytokine release syndrome (CRS) occurred in 10 patients (n=9 grade 1 events; n=1 grade 2 event). The median duration of CRS was 9.23 hours, and two patients received tocilizumab (Actemra) to treat CRS. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.
“With this safety profile we believe it appears more favorable compared to the safety profile of linvoseltamab in the relapsed, refractory setting, with lower rates of grade 3 or higher adverse events, no ICANS events, no treatment discontinuations, and no treatment-related adverse events resulting in death,” Rodríguez-Otero said.
In addition, the rate of grade ≥3 infection rates was lower in patients with HR-SMM compared with relapsed/refractory patients, with grade 3 infections reported in three patients — a COVID-19 infection, a case of Salmonella gastroenteritis, and a Staphylococcus epidermidis bacteremia infection. The non-COVID infections were assessed as treatment-related, and resolved with IV antibiotics.
Rodríguez-Otero reported that a phase III trial comparing linvoseltamab with daratumumab (Darzalex) in HR-SMM is in the works.
