IMS 2025 | Outcomes of limited-duration therapy with bispecific antibodies in RRMM

Currently, bispecific antibodies are given as continuous therapy to disease progression or intolerance to therapy. However, we know that a subset of patients may have sustained remission following a finite or a limited duration therapy. So, we are interested in looking into the subset of patients to identify some of the factors predicting relapse-free survival of therapy. So, in this work that was presented at the International Myeloma Society meeting, we identified 78 patients among the 720 patients who received bispecific antibody in this multinational effort. For the study, we included patients who received a bispecific antibody or a multi-specific antibody directed against BCMA and/or GPRC5D. This could be patients who received a standard of care treatment or an investigational product on a clinical trial. So, patients received treatment but came off for reasons other than disease progression and had ongoing remission for at least three months after therapy. We looked into relapse-free survival, which is of interest clinically. The 24-month relapse-free survival after therapy was 68%. We have seven patients among the 78 patients who have had remission that lasted for 3 years and more; the most extended remission off therapy was about 5 years. We also looked into factors predictive of relapse-free survival in the study; the presence of extramedullary disease, a higher number of prior lines of therapy, mostly 6 lines and more, and a partial disease remission status at the time of treatment discontinuation was associated with an inferior relapse-free survival. Another interesting finding here is the risk of infection after therapy and the IgG kinetics and IV Ig utilization. We know that infection is a serious concern with bispecific antibody therapy, and we wanted to understand whether the infection risk modulates with a finite duration therapy. We found that in patients who have got a finite duration therapy, as in the study, the 24-month cumulative incidence of first high-risk infection was 32 percent. We also found that the rates of recurrent high-grade infection went down with increasing time after therapy. Indeed, 900 days and beyond post-treatment discontinuation, there were no reports of new first high-grade infection. We also looked into IgG kinetics over time. Most of our patients, as we know, have hypogammaglobulinemia and require IVIG supplementation in a real-world setting. So, in this experience, we found that nearly 75% of patients had a low IgG level even 180 days following treatment discontinuation, and 900 days and beyond, 90% of patients had a normal IgG level, showing that there is a slow but steady improvement in the IgG levels with increasing time after therapy. We looked into the trends in IVIG utilization. Nearly 33% of patients in this experience required at least one dose of IVIG in a 30-day window period within the first 180 days of treatment discontinuation. Just like with the IgG levels, we found that IVIG utilization also decreased with increasing time after therapy. Thus, we show in the study that a finite duration bispecific antibody therapy may be a good option at least in a subset of patients. The 24-month relapse-free survival was 68 percent after therapy. The risk of infection does go down with increasing time off therapy, along with a corresponding improvement in the serum IgG level and IVIG utilization.

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