Linvoseltamab Monotherapy Elicits Promising ORR, MRD-Negativity in NDMM

Linvoseltamab (Lynozyfic; Regeneron) demonstrated a generally manageable safety profile across all doses with promising overall response rate (ORR), complete response (CR) rate, and minimum residual disease negativity (MRD-negativity) rates, in patients newly diagnosed multiple myeloma (NDMM).

The study specifically looked at the impact of linvoseltamab, a B-cell maturation antigen (BCMA) and CD3 bispecific antibody, in NDMM patients who were autologous stem cell transplantation (ASCT) eligible (TE) or ineligible (TIE). Results from an abstract on this study were presented at the 2025 International Myeloma Society Annual Meeting in Toronto, Ontario, Canada.¹

Linvoseltamab recently became the first FDA-approved BCMA x CD3 bispecific antibody for the treatment of adults with relapsed or refractory (RR) MM who previously received at least 4 lines of prior therapy.²

Linvoseltamab’s Efficacy and Safety in Multiple Myeloma

The results from the open-label, dose-escalation portion of the phase 1/2 LINKER-MM4 (NCT05828511) study demonstrate the feasibility of linvoseltamab monotherapy in patients who may be eligible for stem cell transplant, and could allow for greater proliferation of the treatment in patients across numerous treatment stages.

Key results from the original phase 1 portion of LINKER-MM4 indicated a robust, 70% ORR in patients with NDMM, with 45% achieving a CR or better. With a step-up dosing regimen, administered once weekly in a hospital setting, it allows for more palatable administration of the regimen, especially for older patients who may not be able to tolerate a long hospital stay, according to Sundar Jagannath, MD, MBBS, professor of medicine at Mount Sinai Health System, who helped lead the LINKER-MM$ investigation.^2,3

Noting that patients with NDMM are more likely than RRMM patients to have intact T-cell fitness, the investigators of this current abstract sought to report the efficacy of linvoseltamab in a newly diagnosed MM population. It is particularly important to elucidate the impacts of linvoseltamab across patient subgroups, including those who are TE or TIE, to ensure no patients are left behind. Furthermore, determining the impacts of linvoseltamab in a population that hasn’t previously received any lines of therapy would provide major indications into its potential as a monotherapy.¹

Linvoseltamab Elicits Robust Effects in Newly-Diagnosed Patients, Regardless of Transplant Eligibility

Patients with previously untreated, symptomatic MM who were TE or TIE were enrolled. TE patients received linvoseltamab induction therapy followed by ASCT and linvoseltamab consolidation, while TIE patients received linvoseltamab monotherapy until their disease progressed. Phase 1/A included a modified step-up dosing regimen and evaluated 3 full doses (50, 100, and 200 mg). Primary end points included incidences of dose-limiting toxicities (DLTs), treatment emergent adverse events (TEAEs), and AEs of special interest.¹

By the first cut-off point of February 11, 2025, 12 patients had received linvoseltamab (50 mg, n = 3; 100 mg, n = 4; 200 mg, n = 5) in phase 1/A, with 75% of these patients being TE. Following a median follow-up of 9.1 months (range: 1.6—12.9), investigator-assessed ORR was 83%, with 75% achieving a very good partial response or better and 58% achieving a CR or better. Importantly, the median time to response was 1.1 months, and 5 of the 7 CRs occurred within 6 months of initiating treatment, indicating a speedy mechanism of action for linvoseltamab monotherapy and highlighting the robust efficacy if a patient has not received prior lines of therapy.¹

Accordingly, the 5 patients deemed MRD evaluable were all MRD negative, as determined by clonoSEQ.¹

Regarding safety, the most common TEAEs observed were increased alanine aminotransferase (any grade, 67%; grade 3–4, 17%) and aspartate aminotransferase (50%). Neutropenia was a common hematologic TEAE (50%, all grade 3–4), while cytokine release syndrome (CRS) was reported in 33% of patients. Infections were a concern, occurring in 58% of patients (grade 3–4, 25%). However, there were no treatment discontinuations due to TEAEs, nor any TEAEs that resulted in death, according to the investigators.¹

These results support the use of linvoseltamab monotherapy in patients with NDMM in the front-line setting. With robust efficacy and manageable safety, linvoseltamab is poised to become a paradigm-shifting treatment in the realm of MM. As the drug continues its proliferation across hospitals and specialty clinics, pharmacists stand to play an essential role in designing orders for linvoseltamab, managing CRS, and assisting nurses in navigating patient care and patient monitoring.^1,4

“Hospital pharmacists have moved far beyond just dispensing—they’re advancing cancer care,” Jagannath noted. “They’ve become indispensable in deliving safe, sophisticated therapies like linvoseltamab.”^1,4

REFERENCES

1. Ferreri C, Shah M, Chakraborty R, et al. Linvoseltamab (LINVO) Monotherapy in Patients (pts) with Newly Diagnosed (ND) Multiple Myeloma (MM): Initial Dose-Escalation Results from the WindowofOpportunityLINKER-MM4Trial. Presented: 2025 International Myeloma Society Annual Meeting; Toronto, Ontario, Canada; September 16 to September 19, 2025. Accessible Online: chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://events.jspargo.com/ims25/CUSTOM/pdf25/AbstractsandEmbargoPolicy.pdf

2. Halpern L. FDA Approves Linvoseltamab-gcpt for Treatment of Relapsed or Refractory Multiple Myeloma. Pharmacy Times. Published July 2, 2025. Accessed September 18, 2025. https://www.pharmacytimes.com/view/fda-approves-linvoseltamab-gcpt-for-treatment-of-relapsed-or-refractory-multiple-myeloma

3. Jagannath S, Halpern L. Expert: FDA-Approved Linvoseltamab Delivers Deep Responses, Offering New Hope for Older Patients With MM. Pharmacy Times. Published July 24, 2025. Accessed September 18, 2025. https://www.pharmacytimes.com/view/expert-linvoseltamab-s-simplified-dosing-expands-access-enhances-tolerability-in-older-patients-with-multiple-myeloma

4. Jagannath S, Halpern L. Video: Pharmacists Take Center Stage in Delivering Linvoseltamab, Advancing Myeloma Care. Pharmacy Times. Published August 1, 2025. Accessed September 18, 2025. https://www.pharmacytimes.com/view/video-pharmacists-take-center-stage-in-delivering-linvoseltamab-advancing-myeloma-care