Linvoseltamab in AL amyloidosis: Early data

By Laura Boyd

Linvoseltamab demonstrates rapid and deep hematologic responses in patients with relapsed or refractory (R/R) systemic light chain (AL) amyloidosis, according to initial results from the phase 1/2 LINKER-AL2 study (NCT06292780) presented at the 31st Annual Meeting of the European Hematology Association (EHA2026 Congress).

In the overall cohort, all patients had a hematologic response, with high rates of complete response (CR). Mean involved free light chain (iFLC) levels normalized by day 15, indicating rapid disease control.

Ashutosh Wechalekar (University College London Hospitals and National Amyloidosis Centre, UK) presented the data, reporting that linvoseltamab monotherapy showed clinically meaningful activity, with deep responses across both dose levels and rapid reductions in iFLC observed within the first treatment cycle.

The phase 1 portion of the LINKER-AL2 study was an open-label trial evaluating linvoseltamab, a BCMA×CD3 bispecific antibody, in patients with R/R AL amyloidosis who had received at least one prior line of therapy. Twenty patients were treated and received step-up intravenous doses followed by subcutaneous administration at either 80 mg (n=7) or 240 mg (n=13) for a 28-day cycle.

With a median follow-up of 9.5 months, hematologic response rates were 71% in the 80 mg cohort and 100% in the 240 mg cohort, with a median response of 1.0 months and 1.6 months, respectively. Hematologic responses deepened over time, with no progression events.

Organ responses were also observed. Among patients evaluable for organ response, renal responses occurred in 73% and cardiac responses in 50%, with many responses achieved within 3 months.

Safety findings were consistent with the known profile of BCMA-directed therapies. No dose-limiting toxicities were reported. Grade ≥3 treatment-emergent adverse events were reported in 65% (n=13 across both dose groups) of patients, of which nine were treatment related. Cytokine release syndrome occurred in 50% of patients; all events were grade 1 or 2, and most were during step-up dosing. Infections were reported in 85% of patients, with grade ≥3 events in 25%.

Wechalekar noted that responses were rapid, with normalization of light chains often achieved within weeks, and that the safety profile was generally manageable in this patient population.

He concluded that linvoseltamab monotherapy “showed encouraging results in R/R AL amyloidosis, for which no approved therapy is available.” The phase 2 study continues with potential registrational intent.

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