Lynozyfic Shows Early Responses for Newly Diagnosed Myeloma

Lynozyfic (linvoseltamab), a B-cell maturation antigen and CD3 bispecific antibody, showed a high overall response rate and a tolerable safety profile when used alone for the treatment of patients with newly diagnosed multiple myeloma, according to initial results from a phase 1/2 study presented at the American Society of Hematology (ASH) Meeting.

The study, which is the first to evaluate a bispecific antibody as a standalone agent in the frontline setting, showed an investigator-assessed overall response rate of 79% across all dose levels. In the 200 mg dose group, which reflects the approved dosage for relapsed or refractory disease, the overall response rate reached 86%. Most evaluable patients achieved minimal residual disease negativity.

These findings suggest that Lynozyfic could offer a simplified highly effective alternative to complex triplet and quadruplet regimens that currently define the standard of care for newly diagnosed myeloma.

Lynozyfic Showed Early Responses

The study enrolled 45 adult patients with previously untreated symptomatic multiple myeloma. The cohort included both transplant-eligible and transplant-ineligible patients.

Responses occurred early, with a median time to partial response or better of 1.2 months.

Among 43 patients evaluable for response, 56% achieved a very good partial response or better, 26% achieved a complete response or better, and most complete responses occurred within months of starting treatment

The efficacy data indicated a dose-dependent pattern. Patients in the 200 mg group (21 patients) demonstrated higher response rates compared with the 50 mg group (20 patients), with 86% versus 70% overall response rates. At the time of analysis, all patients remained progression-free.

Safety and Side Effects of Lynozyfic

Safety findings showed a favorable profile for Lynozyfic compared with historical outcomes for other bispecific antibodies. There were no dose-limiting toxicities reported in phase 1 and no grade 2 or higher cytokine release syndrome side effects.

Cytokine release syndrome was the most common treatment-related side effect and occurred in 44% of patients. All events were grade 1.

Only one patient experienced immune effector cell-associated neurotoxicity syndrome and this grade 1 side effect resolved.

Infections were reported in 84% of patients and were grade 3 to 4 in 33% of those cases. Most infections occurred within the first months of treatment and declined thereafter.

There were a few cases of cytomegalovirus reactivation and none involved organ complications.

The most common blood-related side effects were neutropenia and anemia. Only one patient discontinued treatment because of a side effect.

Patient Demographics From the Phase 1/2 Study

The trial population reflected a diverse group. The median age was 67 years. Regarding racial representation, 18% of patients identified as Black or African American. High-risk cytogenetics were present in 11% of evaluable patients and most patients had high bone marrow plasmacytosis.

The study will advance using 200 mg as the recommended phase 2 dose.

“In general, we feel that this study supports a positive benefit-to-risk profile and there is further exploration of Lynozyfic as a foundation in frontline therapy in newly diagnosed multiple myeloma,” Orlowski concluded.

Reference

1. “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,” by Dr. Robert Orlowski.Presented at: 67thAnnual ASH Meeting; December 6–9, 2025; Orlando, Florida. Abstract 697.

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