$Thumbnail for EHA 2026 | Linker-AL2 study: linvoseltamab monotherapy in relapsed or refractory AL amyloidosis$

EHA 2026 | Linker-AL2 study: linvoseltamab monotherapy in relapsed or refractory AL amyloidosis

Duration: 4:16 718 transcript words EN summary

Video summary

The video discusses linvoseltamab, a novel bispecific monoclonal antibody designed to treat relapsed or refractory AL amyloidosis by targeting the underlying plasma cells that produce harmful proteins. Unlike traditional chemotherapy, this biologic drug functions by binding simultaneously to two different targets: one arm attaches to the plasma cell while the other binds to an immune T cell. This dual-action mechanism brings the T cell directly next to the plasma cell and sends a signal to activate it, effectively instructing the immune system to destroy the diseased cells that generate amyloid-forming light chains. In early safety studies involving the first twenty patients, the treatment demonstrated an excellent safety profile with no severe toxicities that would hinder further research. While minor side effects such as infections were observed, they were generally low-grade and easily manageable. The most significant finding was the drug's ability to induce a rapid and profound reduction in light chain protein levels in the blood; typically, these levels normalized within two weeks of starting treatment and became almost undetectable by the third week. This speed and depth of response represent a major improvement over previous therapies, offering patients a critical opportunity to immediately halt the production of amyloid precursors. The administration protocol involves an initial intravenous infusion for the first two doses, followed by subcutaneous injections under the skin, usually in the abdomen. The dosing schedule begins with weekly injections for eight weeks and transitions to monthly doses thereafter, with treatment typically continuing for twelve months but potentially extending up to two years if necessary. These results from the early phase study highlight linvoseltamab as a highly tolerated option that achieves deeper responses than almost any other chemotherapy used in amyloidosis, marking a transformative potential for patients suffering from light chain amyloidosis. Looking ahead, the research is moving from this safety-focused phase one trial to a phase two trial aimed at evaluating the drug's effectiveness in a larger patient population. Recruitment for this next stage is expected to be completed over the coming year or two, with results intended to support regulatory licensing for patients who have relapsed or refractory disease. Additionally, there are hopes to eventually study the medication in newly diagnosed patients, further expanding its role as a leading treatment option that combines safety, rapid action, and deep efficacy to improve outcomes for those with AL amyloidosis.

Read the full video transcript

[music] >> So then we set them up is a monoclonal antibody. It's a protein that binds to plasma cells. It's a bispecific antibody, which means that it binds to two different things. It has got one arm which binds to the plasma cell. It's got a second arm which binds to an immune cell called T cell. The T cell binding arm, the immune cell binding arm also has a little signal which tells the T cell to become active and gives it a signal to kill the plasma cell. So it really mediates the immune cell to come right next to the plasma cell and then tells the immune cell kill this plasma cell. So that's really what this antibody is meant to do. This antibody is uh given initially as an intravenous infusion as a drip for the first two doses. And then after that it's given as a subcutaneous injection under the skin usually in the tummy. Uh it's given once weekly for the first 8 weeks and then it's given once a month thereafter and in this trial we did usually 12 months of treatment with a potential to extend it to 2 years if it was necessary. So the LINKER-MM1 trial is investigating uh linvoseltamab as a treatment for the plasma cell that produced amyloid forming protein is investigating as a treatment for the plasma cell dyscrasia that that underlies systemic amyloidosis. This drug is intended to kill the plasma cells with a view to reducing the amyloidogenic light chain protein in the blood. And certainly in this trial what we were able to show and this was a very early phase study, which means that we were looking mainly at the safety of this drug uh to show that we can deliver it safely to patients and certainly in the first 20 patients that were treated and in the abstract that we presented we saw no toxicities or side effects that would limit us from studying this drug further. Uh we saw some uh some toxicities like infection, but generally they were fairly low grade and they were very very manageable. Uh what we saw in a striking way was that we were measuring these uh the light chain protein amyloid forming protein in the blood for all of these patients every week when we started the treatment and we saw a very dramatic reduction in the light chain protein. So, typically by second week, so 14 days after the drug was given, so after the first two doses, almost every patient had normalized their light chain protein and typically by the third week the light chains were almost undetectable. And that is a very critical finding for amyloid patients where we really want a deep and a rapid response and this this drug achieves both. And the responses that we're seeing with lenalidomide are much much faster than responses we've seen almost with any other drug um apart from other similar drugs that have been studied in amyloidosis. So, this really is a treatment which has a potential to transform patients with light chain amyloidosis where we immediately want to stop the production of the amyloid precursor protein, the light chains. So, these results represent a huge advance for patients with AL amyloidosis. This [music] is a biologic drug, it's not a chemotherapy, it's a monoclonal antibody, it's incredibly well tolerated and we see very fast and very rapid responses. We see deeper responses than what almost every other chemotherapy that we've used in amyloidosis. So, it does represent a huge advance for treatment of light chain amyloidosis. Now, this was a phase one trial, which means we were looking at safety. We are now studying this drug in a phase two trial where we're actually looking at effectiveness with a view that the phase two will lead to this drug being licensed in patients with relapse refractory amyloidosis. >> [music] >> So, the phase two trial will complete its recruitment over the coming 1 to 2 years. And once those results are analyzed, they will be presented to the regulatory authorities with a view to licensing. And we're also hoping that we will be able to study this drug in patients with newly diagnosed light chain amyloidosis. >> [music]