IMS 2024 | The efficacy of linvoseltamab in prespecified high-risk subgroups in the LINKER-MM1 study

The LINKER-MM1 study is a Phase I/II study of an agent called linvoseltamab in relapsed/refractory myeloma. Linvoseltamab is a BCMA-CD3 bispecific antibody and it’s being investigated in relapsed/refractory myeloma in patients who have had at least three prior lines of therapy and triple-class exposed or triple-class refractory. Specifically for this meeting, we’re presenting the data on four different high-risk subgroups that have been pre-identified, predefined at baseline. So they are the people who are over 75 years of age, patient with high-risk cytogenetics, advanced stage, and also patients with extramedullary disease. So we’ve already reported out the efficacy based on overall response rate, which is a primary objective of the study. In this one, we’re going deeper into the detail to also look at longevity of those response, so in the snippets, response rates high all across four different subgroups. The extramedullary disease subgroup numerically had a little bit lower response rate of about 53%, while everyone else we’re looking at a response rate that is in the 70%. Longevity of the response is certainly there as well, right now progression-free survival has not been reached in all subgroup except the EMD population which also unfortunately has a shorter progression-free survival. On the safety signal, which is important particularly for folks who are older, we actually see that response was not only sustained but also there’s not a lot of new side effects being identified. Infection is common for patients getting this kind of treatment and linvoseltamab also has high infection rate overall of about 70% and about 30% being grade 3, 4. But the kind of infection that makes people stop therapy is quite rare and it didn’t seem to be any different in between the younger than 65, 65 to 75, and also folks who are older than 75. The way the treatment was given schedule-wise is also a little bit different comparing to other agents. It’s given step-up dosing day one and eight so just a week apart, and then patients are on weekly therapy from that week three through week 13. Then they go down a little bit faster comparing to other programs to every two weeks from that week 14 all the way to week 24. Now, the major difference is in that patients with deep response, VGPR or better, actually go down to just every four weeks so whether that plays a role in decreasing the chance of treatment-related side effects and keeping people on therapy longer and translates to the long-term benefit, which is left to be seen.