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

Hi everyone, my name is Cindy Chmielewski. 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. I'm also a research advocate and I'm a research advocate on Dr. Arazzo and actually not just hers but the LIMITEC 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 inpatient friendly. Look at the clinical data, look at the clinical data, look at the clinical language so that patients understand. And I'm really happy to be a patient advocate on this trial because it's a limited duration toclistamab trial and we know that toclistamab 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 toclistamab and maybe stop some of those infections. So Dr. Arazzo is going to now talk about this. Absolutely. Thank you Cindy. You can introduce yourself. Sure. Yeah so I'm Dr. Beatrice Arazzo. I work at Thomas Jefferson University and on behalf of my colleagues through the LIMITEC study including PI and mentor Dr. Al Garfel and on behalf of our our advocates I'm glad to share a little bit more about the study. And so as Cindy mentioned toclistamab which is approved for patients with refractory myeloma and greater than four prior lines of therapy. It is very effective and responses are seen in many patients. It's approved as a continuous treatment but that has come with the expense of continuous high rates of infections including severe infections and indeed it is unknown whether continuous treatment is is also needed from an efficacy perspective. And so this compelled the study which opened now over two years ago. looking at who had a good response to ticlistamab after six to nine months of treatment defined as a very good partial response or better to discontinue these therapy and undergo very close observation off of treatment the study also looks at response to retreatment of ticlistamab 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 ticlistamab and and with secondary endpoints being the rates of infection and and other efficacy parameters and our abstract which will be presented tonight as a poster it shows outcomes for the ticlistamab and the 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 the efficacy stand perspective but even before that we've obviously been capturing parameters of immune recovery and we'll show those trends and the the poster later today but shows that with discontinuation of ticlistamab there was a gradual recovery of cd-19 an uninvolved light change 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 proteasome inhibitor, overall reflective of a heavily pretreated group. 22% of those patients had previously received a treatment that targets BCMA. Nine of those 50 patients had received CAR T-cell therapy before. Of those 50 patients, 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-1 when patients remained off of treatment. Regarding re-treatment, many of those who did experience relapse within 12 months of discontinuation of teclistamab, all of those patients did not respond to restarting teclistamab when the multiple myeloma was progressing. And only one of the three who had a relapse in the past year, or a later progression after one year off of treatment, has manifested a response. And so, surprisingly to us, even though the outcomes and the time that patients remain on remission off of teclistamab is very comparable to if they had remained on teclistamab, the fact that most of these patients do not respond to teclistamab coming on board again for treatment, along with some of our our pathology and laboratory findings, that we have seen, that really suggests that BCMA is no longer expressed on the multiple myeloma cells, or there is a new mutation in the BCMA gene, it kind of 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 to the next stage of treatment, and we have limited experience with those who are progressing to the next stage of treatment, after a long time off of teclistamab, but that does seem to be the overwhelming case for those who experience progression early on, even if that is the minority of patients. And so we're excited to continue looking at these who have done very well off the teclistamab for a while, understanding whether this is associated with fewer infections and what it means more long-term for their possibility of re-response to teclistamab. 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 teclistamab. Encouragingly, even though all of these patients did not go on to respond to teclistamab re-challenge, five out of six of those patients who then were treated with talquetamab had an excellent response. who then were treated with talquetamab had an excellent response. who then were treated with talquetamab had an excellent response. who then were treated with talquetamab 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. I'm 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 teclistamab, maybe in some of the other bispecific antibodies, we can look at a limited duration for them, which will be much nicer on patients. So thank you. 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