IMS 2025 | CMV and other viral reactivations in patients with RRMM treated with BCMA-targeted bispecifics

Currently, we’re all using BCMA-targeted bispecific antibodies for patients with relapsed multiple myeloma. We are aware that there are a number of infectious complications which can be mitigated by antibacterial, antiviral, prophylaxis, and IVIG. But what we’re also seeing is the incidence of more opportunistic infections. And if you start testing patients, then you do see that patients seem to reactivate CMV. Now, of course, this is of concern because of the immunosuppressed nature of these patients and the potential of the CMV reactivation causing CMV disease. Currently, when you look at the guidelines, it’s not very clear how this should be managed. And when the IMWG bispecific guidelines were written, a survey was performed by the IMWG and there was no real consensus as to how to manage this. To try and guide future guidelines, we in the UK decided to analyze our data for patients receiving BCMA bispecific antibodies and to understand what the rates of CMV activation and disease were. At University College Hospital, we screened all of our patients receiving BCMA antibodies and showed that actually quite a high proportion of patients do get CMV reactivation. But what was very clear was that we had no actual events of CMV disease. So essentially what we were seeing was very low level CMV activation. And when you dive into the actual levels of transcripts of CMV, then most of them were below quantifiable limits, which is actually could be seen as being CMV negative. Now, when you look to see what happens to those CMV levels, then we do see that those CMV levels can go up. And actually, whether you stop or continue treatment didn’t seem to alter the trajectory of the CMV. Certainly for some patients we did interrupt the bispecific antibody and the CMV titers went down. But overall when we looked at the data actually we determined that there was no need to be routinely testing for CMV PCR in patients and whether we should stop bispecific treatment should be made on a case-by-case basis and couldn’t make any firm recommendations. But certainly, if you were concerned, then stopping the bispecific antibody would be appropriate as we do see recovery of CMV levels thereafter.

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