LINKER-MM1: Efficacy and Safety Data of Linvoseltamab 200 mg in MM

Joshua Richter, MD, associate professor of medicine, hematology and oncology at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and the director of myeloma at the Blavatnik family Chelsea Medical Center, evaluates the efficacy and safety data of linvoseltamab (REGN5458) for the treatment of patients with multiple myeloma.

Findings of 2 different dose levels of linvoseltamab were assessed in the phase 2 LINKER-MM1 study (NCT03761108) and presented at the 20th International Myeloma Society Annual Meeting.

According to Richter, linvoseltamab given at the 200 mg dose demonstrated higher efficacy than the 50 mg dose across subgroups enrolled in the trial, including high-risk and high tumor burden subgroups. The safety profile of the agent was similar at both doses. These data support 200 mg of linvoseltamab as the recommended dose for future studies.

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0:10 | We saw a 71% response rate in the 200 mg dosing cohort. The median progression-free survival is not yet reached, and although we can't make any predictions just yet, the curve is looking kind of flat. So fingers crossed it's going to be very durable. But we're starting to see very prolonged responses. Anecdotally, I have some patients in my clinic who even received the earlier doses that are still on q2 weekly dosing, and still in remission on week 100, and on week 180, just continuing to maintain responses. Again, my personal experience is that the drug has been very efficacious.

0:45 | Now, we have to talk about the toxicity because what are we giving up for that high efficacy rate? When it comes to these types of therapies, there are immediate toxicities and the long-term toxicities. Long-term toxicities are fairly similar as we see with other assets within the class of infections. We definitely see infections with the drug, although the overwhelming majority of these are grade 1 and grade 2. There were a few cases of PJP [pneumocystis jiroveci pneumonia] however, those patients were not on PJP prophylaxis. For anyone who took PJP prophylaxis, there was no evidence of PJP pneumonia.

1:19 | From a median toxicity standpoint, 1 of the most exciting things we saw was the relatively low rate of CRS [cytokine release syndrome] within linvoseltamab. Now again, we can't do cross trial comparisons. But in myeloma we always say to take a nice deep breath, and then we do cross trial comparisons. If you look at other similar drugs in the asset class, the CRS rates are 70%-80%. The CRS rate here at the 200 mg dose was around 45%. Again, the overwhelming majority of this is grade 1, grade 2. There's only 1 grade 3 in the mix. Whereas a lot of the assets are looking to add prophylactic tocilizumab to bring the CRS rates down, the starting CRS rate here was already quite low. To us, that provides the great balance between safety and tolerability. And again, overall, I think if we approach the drug with the appropriate ion prevention, early intervention with CRS appropriate use of IVIG and anti infective prophylaxis, we're able not only to achieve those deep responses, but maintain them and have patients avoid some of the adverse event pitfalls that we can see anytime we engage in T-cell redirection.