LimiTEC: Limited-Duration Teclistamab Results | Beatrice Razzo, MD & Cindy Chmielewski

Hi everyone, my name is Cindy Shmuleski. I've been living with multiple myeloma since 2008. I am, some of you may know that I am the Health Tree University Curriculum Director for multiple myeloma, but I'm also a research advocate. And I'm a research advocate on Dr. Arazo and actually not just hers, but the Limitech trial. And what does a research advocate do? Well, a research advocate is kind of like a liaison between the research community and the patient community. And I bring the patient perspective when trials are designed. I look at the protocols to see if they're not burdensome on the patient and they're patient-centric. And then we do things like this. We share the research with our patient audience. We look at patient-facing materials, make sure they're in patient-friendly language so that patients understand. And I'm really happy to be a patient advocate on this trial because it's a limited duration to Toclistimab trial. And we know that Toclistimab is a great drug, but it causes infections. And sometimes those infections are serious. So it would be really nice if we could limit the duration of Toclistimab and maybe stop some of those infections. So Dr. Arazo is going to now talk about this. Absolutely. Thank you, Cindy, for the opener. Yes. So I'm Dr. Beatrice Arazo. I work at Thomas Jefferson University. And on behalf of my colleagues through the Limitech study, including PI and mentor Dr. Al Garfel, and on behalf of our advocates, I'm glad to share a little bit more about the study. And so as Cindy mentioned, Toclistimab, which is approved for patients with refractory myeloma and greater than four prior lines of therapy, is very effective. Responses are seen in many patients. It's approved as continuous treatment, but that has come at the with the expense of continuous high rates of infections, including severe infections. And indeed, it is unknown whether continuous treatment is also needed from an efficacy perspective. And so this compelled the study, which opened now over two years ago, looking at patients who had a good response to Toclistimab after six to nine months of treatment, defined as a very good partial response or better, to discontinue the therapy and undergo very close observation. Off of treatment, the study also looks at response to retreatment of Toclistimab Toclistimab. When patients experience disease growth or progression, overall asking the question whether intermittent dosing overall yields to comparable efficacy to the Majestic One study, which led to the approval of Toclistimab and with secondary endpoints being the rates of infection and other efficacy parameters. And our abstract, which will be presented tonight as a poster, it shows outcomes for 50 enrolled patients who have at least one month of follow-up data. I'll talk a little bit about the efficacy stand up perspective, but even before that, we've obviously been capturing parameters of immune recovery and we'll show those trends in the poster later today, but shows that with discontinuation of Toclistimab, there was a gradual recovery of CD19 and uninvolved light chains that gradually rose throughout the first year off of treatment. Our infections data is not mature yet to be presented and discussed and that will come in subsequent presentations. Of these 50 patients, the average number of lines of therapy they had received were four. 80% were what we call triple class refractory, meaning they had been resistant to a CD38 monoclonal antibody, an immunomodulatory agent, and a proteosome inhibitor, overall reflective of a heavily pre-treated group. 22% of those patients had gotten previously received a treatment that targets BCMA. Nine of those 50 patients had received CAR T cell therapy before. Of those patients enrolling, 72 were in a very good partial response. The other 28 were in a complete response or deeper, and of those patients in VGPR, many would have also been in complete response just by looking at the serum criterion. Our poster tonight reports how patients did after an average of 12 months of follow-up. So the time on study ranged from one month to greater than two years for several of our patients. Amongst those, the majority of patients were able to remain off of therapy even after 12 months of follow-up. Encouragingly, the curves and trends in terms of progression-free survival that we observed appeared very comparable to those seen in Majestic One when patients remained off of treatment. Regarding re-treatment, many of those who did experience relapse within 12 months of discontinuation of Teclistomab, all of those patients did not respond to restarting Teclistomab when the multiple myeloma was progressing. Only one of the three who had later progression after one year off of treatment has manifested a response. Surprisingly to us, even though the outcomes and the time that patients remain on remission off of Teclistomab is very comparable to if they had remained on Teclistomab, the fact that most of these patients do not respond to Teclistomab coming on board again for treatment, along with some of our pathology and laboratory findings that really suggest that BCMA is no longer expressed on the multiple myeloma cells or there is a new mutation in the BCMA gene, it kind of makes, portrays a consistent picture that an early selection of BCMA negative or mutated clones is a large driver of relapse in this patient population and we have limited experience with those who are progressing after a long time off of Teclistomab, but that does seem to be the overwhelming case for those who experience progression early on even if that is the minority of patients. So we're excited to continue looking at these who have done very well off Teclistomab for a while, understanding whether this is associated with fewer infections and what it means more long terms for their possibility of re-response to Teclistomab and then those who've unfortunately experienced earlier progressions, I think this continues to add a lot of important information for us regarding how patients relapse and what the next best options for those are after Teclistomab. Encouragingly, even though all of these patients did not go on to respond to Teclistomab re-challenge, five out of six of those patients who then were treated with Talcuitomab had an excellent response and so we're excited to continue expanding in this cohort and really understanding what the best way to treat patients after an early or later relapse, but likely safely having a period off of therapy. And I'm very excited about this trial. I can't wait for further data to come up. Curious about what you find out about the infection rates later on. I know it's immature data and hopefully once we started this with Teclistomab, maybe in some of the other bismacific antibodies, we can look at a limited duration for them and which will be much nicer on patients. So thank you. Yeah, thank you. If our videos have helped you in any way and you're able to please consider making a donation to help us continue this important work. Your gift will go three times as far when we reach $500,000 by the end of the year. Every contribution, big or small, makes a difference and we're deeply grateful for your support.