Response Patterns of Linvoseltamab for Relapsed/Refractory Multiple Myeloma With Hans Lee, MD
At the recent American Society of Hematology (ASH) Annual Meeting, Dr. Hans Lee, the Director of Multiple Myeloma Clinical Research at MD Anderson, presented his team's research from the LINKER-MM1 study, which sought to evaluate response patterns of linvoseltamab for relapsed/refractory multiple myeloma. Later, Dr. Lee sat down with Oncology Data Advisor to further discuss his study, the results he was able to present, and his team's next steps for this research.
Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we are at the ASH Annual Meeting with Dr. Hans Lee. Thank you so much for being here today. Would you like to give us an introduction of yourself and your research interest?
Hans Lee, MD: Thank you, Lyn. My name is Hans Lee. I'm an Associate Professor at MD Anderson Cancer Center in Houston, Texas, in the Department of Lymphoma/Myeloma. Also, I'm the Director of Multiple Myeloma Clinical Research at MD Anderson. I treat patients with multiple myeloma, and I'm engaged in clinical research in multiple myeloma with new therapies that might be effective in multiple myeloma.
Oncology Data Advisor: Incredible. And thank you again for your time today. First question I wanted to ask, just to get into things, is could you give a brief overview of the LINKER-MM1 study and what it set to accomplish?
Dr. Lee: The LINKER-MM1 study is a clinical trial evaluating a drug called linvoseltamab, which is a BCMA bispecific T-cell antibody in relapsed/refractory multiple myeloma. There are two parts of the study. The phase 1, dose escalation, tried to identify the optimal dose of linvoseltamab. The phase 2 part of the study looked at two separate doses of linvoseltamab, at either 50 mg or 200 mg, to optimize the dose selection of the drug.
Oncology Data Advisor: Incredible. Thank you for that. And what were the results that you presented from the study?
Dr. Lee: So, at this year's ASH meeting in 2023, it really reflects two key things. One is more mature, longer follow-ups. The median follow-up at this year's ASH meeting is reporting data with a median follow-up of 8.1 months. In addition, the second key aspect is this is the first time that the primary end point of the study, which is overall response rate as adjudicated by the independent review committee (IRC), is being reported in the study.
In summary, in the 200-mg dose cohort, which is the recommended dose of linvoseltamab moving forward, based on earlier safety and efficacy data, 117 patients were enrolled in the study. They were heavily pretreated with a median of five prior lines of therapy. Eighty percent of patients were called triple-class refractory to the three main myeloma drugs, immunomodulatory drugs (IMiDs), protease inhibitors, and anti-CD38 monoclonal antibodies. Over a quarter of the patients were over the age of 75.
What the results showed was that the overall response rate at the 200-mg cohort was 69%, with the majority of patients attaining what we call a very good partial response—so a deep response—of 59%.
I would mention though that actually just early this week, there was a press release with an even later data cut of linvoseltamab at a median follow-up of 11 months. What we saw was that actual responses seemed to deepen over time. So, with this longer follow-up at 11 months, the overall response rate by the IRC was 71%, with a 46% complete response rate.
Oncology Data Advisor: I'm curious, were there any limitations in this study that your team experienced that you'd like to address in a phase 3 trial?
Dr. Lee: In terms of the safety profile of this study, one thing that we're always watching very closely is cytokine release syndrome (CRS) and the rates of cytokine release syndrome. Overall, the rates of cytokine release syndrome were low in this study, 46%, the majority of which being what we call grade 1 in severity.
Another adverse event of special interest is infection, so about 37% of patients had grade 3 or higher infection. So, moving forward, we're always looking for ways to optimize CRS management and infection management. And of course, this will be looked at very closely in future studies with linvoseltamab.
But really, the positive data with the LINKER-MM1 study has then led to a number of other studies evaluating linvoseltamab and other areas of myeloma. For instance, the LINKER-MM3 study is a randomized space evaluating linvoseltamab compared to standard-care therapy and comparing specific to elotuzumab, pomalidomide, dexamethasone, and earlier lines of prior therapy. This will hopefully provide confirmation of the efficacy of linvoseltamab in a randomized study in this particular patient population.
Oncology Data Advisor: Since multiple myeloma is such a rapidly evolving treatment landscape, how is linvoseltamab a unique treatment option for relapsed/refractory myeloma patients?
Dr. Lee: That's a great point you make, Lyn, and that the treatment landscape for multiple myeloma is evolving very rapidly. We're very excited that there's a number of new immunotherapies available for our patients, including bispecific T-cell antibodies and chimeric antigen receptor (CAR) T therapies that target different antigens such as BCMA and GPRC5D.
What we're seeing is that these drugs are very effective in late relapsed/refractory multiple myeloma. Ultimately, as the treatment landscape evolves, these treatments will be used in earlier lines of therapy, and even newly diagnosed patients, because we're really seeing incredible efficacy with these therapies, and the safety profile also seems to be promising with many of these therapies, as well. So, the risk-benefit ratio is strongly in favor of these treatments.
Oncology Data Advisor: Incredible. Thank you. We're definitely excited to hear more about the future results and studies. So, thank you so much for your time today, Dr. Lee. We really appreciate it.
Dr. Lee: Thank you so much, Lyn.
About Dr. Lee
Hans Lee, MD, is the Director of Multiple Myeloma Clinical Research at and an Associate Professor in the Department of Lymphoma Myeloma at MD Anderson Cancer Center in Houston, Texas. Dr. Lee's research interest is centered around multiple myeloma, developing novel treatment options, and advancing patients' care and treatment processes.
For More Information
Jagannath S, Richter J, Dhodapkar M, et al (2023). Patterns of response to 200 mg linvoseltamab in patients with relapsed/refractory multiple myeloma: longer follow-up of the LINKER-MM1 study. Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 4746. Available at: https://ash.confex.com/ash/2023/webprogram/Paper177968.html
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of Oncology Data Advisor.