Real World Experiences of Patients Treated with Teclistamab | Shonali Midha, MD | IMS 2023

I'm Shnally Mehta. I'm one of the physicians at Dana-Farber Cancer Institute in Boston, Massachusetts. Today, I'll be discussing our results from the real-world experience of Toclystumab, a BCMA-directed bispecific antibody in the relapsed refractory multiple myeloma patient population. So we evaluated at a single center at Dana-Farber our experience in a retrospective analysis from the time of FDA approval in October 2022 up through August 15, 2023. We had looked at patients that had completed ramp up with Toclystumab, so the first three step-up doses, and included patients that had progressed or had died due to toxicity or infection-related complications prior to the day 30 response assessment, including up to 56 patients in our cohort. We found that the patients that we were treating were more heavily pretreated as well as patients that had a larger burden of disease. They tended to have a higher stage, RISS2 or 3. More patients had extra medullary disease, CNS disease, and renal dysfunction as compared to Majestic 1, which was the trial that led to the FDA approval of Toclystumab in the relapsed refractory space. We had of the 56 patients, 20 that had received prior BCMA-directed therapies, 13 that had received prior BCMA CAR, and 13 that had received prior BCMA antibody-drug conjugate like Bilanthamab and Matfidotin. And so we did find that those patients, compared to those that did not have prior BCMA, were more likely to have a better performance status. However, we're also more heavily pretreated, receiving nine prior median lines of therapy as opposed to six in our overall cohorts. In regards to toxicity, we saw similar rates of toxicity compared to Majestic 1. We had about 51.8% all-grade cytokine release syndrome that was observed, which is an inflammatory state associated with T-cell-engaging products. However, we only had one patient that had a high-grade toxicity event, equating to about 1.8%. We also only had one patient with a neurotoxic event that was reported, even though we had a higher proportion of patients with central nervous system involving disease. We did not have any grade III neurotoxicity events or high-grade neurotoxicity events, and no late neurotoxicity events have been reported. In regards to the survival outcomes, we saw an overall response rate of 53.6% in our overall cohorts. So we saw a lower response rate in prior BCMA-treated patients at 45%, largely related to prior BCMA CAR T therapy with a response rate of 30.8, as opposed to patients with prior belantyma amafodotin with a response rate closer to our overall survival at 53%—our overall response rate at 53%. We also saw in patients with high-risk features, such as with extra medullary disease, a response rate that was lower than the total cohort at 37.5%. Within Toclistomab treatment, we still see infection signal as a significant signal. We experienced—sorry, it's going to take me a second to remember the numbers. So we still saw a significant infection signal within our Toclistomab-treated patients with 37 infections and 26 patients, nearly half of which were high-grade infections or required inpatient hospitalization and management. The majority of those infections were respiratory, being upper respiratory infections or pneumonia. However, we did also see 13% skin and soft tissue infections, as well as 13% gastrointestinal infections, with the remainder made up of urinary tract infections, infections in the bloodstream. Of the upper respiratory infections, about 45% were COVID-related. That being said, we did not have any Toclistomab-related infection deaths in our cohorts. In regards to survival outcomes, we saw a medium progression-free survival in our real-world cohort of 4.7 months. And when we look at that broken down by prior BCMA therapy in patients that had received prior BCMA therapy, the medium progression-free survival was 4 months, versus in those that were naive to buy BCMA-targeted products was 4.8 months. So overall, we saw very similar overall responses compared to the majestic trial, the original trial that led to the approval of Toclistomab. However, we did see adverse effect on progression-free survival based on risk factors such as high stages, our ISS stage 3, our high disease burden, extramedullary disease, or in our case, we saw a significantly increased risk of a poor response or progression-free survival with an increased ferritin or inflammatory response. Sorry, do you have more? No, I can stop there. I don't know if that's too long or too short. Oh, it's like it's told. Okay. I'm not done. I'm not done. No, no, I don't have too much more. So we're excited to present these results but have more work to do in understanding the relation of duration of BCMA-targeted treatment to response as well as durability of response and are working on looking into that further with correlative studies, understanding immune subset T-cell and immune fitness. Thank you.