EHA 2026 | ImmunoPRISM results: teclistamab improves depth of response and PFS compared with Rd in HR-SMM

Yeah, so teclistamab is a BCMA-directed T-cell engager that is approved for patients with relapsed/refractory myeloma. We’ve seen recent data in the earlier disease setting in one to three prior lines of therapy where teclistamab shows substantial improvements compared to standard regimens in relapsed/refractory myeloma. So that really sets the premise for this ImmunoPRISM trial, which is the first trial looking at teclistamab in patients with high risk smoldering myeloma that have a high risk of progression to overt myeloma. The rationale was that if you use teclistamab in patients that have a more intact immune system, you’re going to see potentially even more heightened activity and hopefully a better safety profile. And historically, prior to the approval of daratumumab, there really wasn’t anything available for patients with high-risk smoldering myeloma in terms of early intervention, but there were some previous studies of lenalidomide-based approaches that were shown to be superior to observation. So we wanted to do a randomized trial, and this is a phase 2 study, and we used lenalidomide and dexamethasone as a comparator arm compared to teclistamab. 

So this trial enrolled patients with high-risk smoldering myeloma using various established criteria. We initially had a six-patient safety run-in and then randomized patients to lenalidomide and dexamethasone for two years versus teclistamab for initially two years, but we amended the protocol to reduce the time of therapy to 12 months based on the strong efficacy signal we were seeing. So ultimately, 59 patients were enrolled into the study, and a total of 45 were treated with teclistamab, and 14 were treated with lenalidomide and dexamethasone. 

The safety profile was overall quite favorable, so CRS occurred in almost about two-thirds of patients, but all low grade. And then infections, which is a common issue with bispecific antibodies, we saw a much lower incidence of grade three infections in only 20% of patients, which was actually similar to the control arm. So there really wasn’t an increase in infections, similar to what we see in people with relapsed/refractory myeloma. And I think what was really exciting was just the responses that we saw. So 75% of patients achieved a complete response to therapy and 82% of patients were MRD negative at 10 to the minus five just with single agent teclistamab. So this is a really effective regimen and these numbers seem a bit higher than what we’ve seen in this space in other sort of more conventional combination type therapies. So a time-limited therapy with a bispecific antibody leading to an MRD negativity rate of over 80% was very encouraging. And what we were really impressed with was the data for progression-free survival. So they had two multiple myeloma on this study, five of them in total. The majority of these, all of these progressions were bone complications, bone lesions that patients develop. But the two-year estimated progression-free survival was 92% with teclistamab and 51% with the control arm. So a pretty striking progression-free survival benefit that we saw. So I think, you know, really deep responses with this single agent in the high-risk smoldering population. Overall, the safety profile was, I think, a little bit better than what we expected, you know, compared to what we see with the relapse patients. And really, this MRD negativity rate and the durability of MRD negative responses is really going to be key going forward to know, you know, what the long-term outcomes are for these patients.

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