MajesTEC-2 Trial | Emma Searle, MBChB MA MRCP FRCPath PhD | ASH 2022

Hi, I'm Emma Searle. I'm a consultant hematologist at the Christie Hospital in Manchester, England, and honorary senior lecturer at the University of Manchester. I'm here at ASH 2022 presenting the early findings from cohort E of the Majestec II trial, in which patients with relapsed multiple myeloma were treated with Teclastomab, Daratumamab and Linamide. I think this data is important because it's the first of data sets that we're starting to get around how we might use these agents at an earlier line of therapy. So patients that were included in this study had had between one and three prior lines of therapy and an average of two lines of therapy. It's also some of the first data that we're seeing with BCMA targeting by specifics in combination with other myeloma drugs. And I think what we've learned is that these are very powerful anti-myeloma tools when used in combination in earlier lines of therapy. We saw a very high overall response rate of 94% with a complete remission rate of 55% and a very good partial response or better rate of over 90%. So the vast majority of patients were responding to the treatment. It's a bit too early to say how durable those responses are going to be because their average follow-up was around about eight months. But at the point that we analysed the data ahead of the conference, we could see that over 80% of patients were still on treatment and responding. So I think these are exciting new treatments, but they also bring with them side effects. And we've learned a bit more about the sort of side effects that occur when these by specific antibodies such as teclistomab are used in combination. We do see that patients can drop their blood counts. In particular, they can become neutropenic and we need to keep an eye out for that and manage it appropriately. In terms of the early side effects, so cytokine release syndrome in which patients experience temperatures, they can drop their oxygen levels, they can drop their blood pressure. That can occur and did occur in the majority of patients who were right at the beginning of treatments. But I think we've all gained a lot of experience with managing those side effects and I think we didn't see severe versions of that. I don't feel it's a big concern for this agents going forward. I think the area of data where we do need to apply some caution is really around infections. So 90% of patients experience an infection. Fortunately, most of these were not serious infections, but we did have about a third of patients who experienced more serious infections, including severe COVID-19. And we did sadly lose two patients out of the 32 who were treated in this study to infection, one from COVID-19 and one from more generalized sepsis. So they had a very severe skin infection relating to another medical disorder that they had. And that sadly took their life. So moving forward, as hematologists, we're very used to using treatments that can affect the immune system. I think these agents have very high efficacy and I think we all want to see them moving forward into clinic. But we do need to continue to understand more about the side effects and how to keep patients safe when they're receiving these treatments. The next step for Teclistumab going forward is the planned up and coming Majestex 7 trial, in which we'll compare this combination of Teclistumab, Daratumumab and Lenalidomide against Daralendex. And I think that will be really interesting and important data to see a direct head-to-head comparison against the standard of care. And I look forward to seeing that data written at the next ASH conference. We couldn't do these trials without the patients who give up their time to participate. And I'd really like to thank all of the patients and their families and caregivers. And in terms of what else has excited me, it's ASH. This is a very exciting time to be a myeloma doctor. For years, we've had versions of the same types of treatments, whether that's immunomodulatory drugs or proteasome inhibitors, or the anti-CD38 monoclonal antibodies. And we've now got a whole tranche of new immunotherapy options, new targets that are going to provide really effective drugs for patients going forward. I still don't think we're there with having cured myeloma, but I think we're really making progress now in having treatment options for patients that can produce deep and long remissions and to keep people well as long as possible.