EBMT 2026 | The potential of soluble BCMA as an emerging biomarker in BCMA T-cell-redirecting therapies

A few years ago we had a very big problem in the multiple myeloma field. We had a problem in triple-class refractory patients. The LOCOMMOTION and MAMMOTH studies showed very bad results with overall survival less than one year. And then BCMA-directed therapies revolutionized this field. Well, now we have CAR T-cell and bispecific antibodies with a deep and durable response, even in patients who are relapsed and refractory. So we have one solution. But what’s the problem? We have patients that respond very well to these therapies and we have other patients that don’t show a response. So we think that it’s very important to know why one patient is going to respond and why another patient is not going to respond. So we want to design strategies to see why one patient is going to respond and another not. 

One of these strategies is biomarkers. One of these biomarkers is a soluble BCMA. So we designed one prospective study in which we included 160 patients. From these 160 patients that we included between 2022 and 2025, we selected 36, 20 with CAR T-cells and 16 with bispecific antibodies. We selected these patients because we monitored soluble BCMA in different moments, from baseline initiation, day 28, 56, 100, six months, 12 months, and progression. Our objectives were mainly three. The first one to correlate soluble BCMA with tumor burden markers. The second one to study if soluble BCMA can be a dynamic biomarker. And the third one is if soluble BCMA can predict early response. Baseline characteristics were similar in both groups. 

And regarding the results, the first question to correlate soluble BCMA with tumor burden markers. Well, we saw a moderate correlation between bone marrow plasma cell infiltrations and also with monoclonal serum protein. About the second question, about dynamic biomarkers, we saw that soluble BCMA in patients that achieve response have a big decrease by month one, and this decrease maintains stable in patients that achieve response. Patients that do not achieve response have levels that were a little bit higher. And when a patient is going to relapse, we saw that soluble BCMA levels increased. We compared in both groups, in CAR T-cells and bispecific antibodies, and we see similar results. Maybe in CAR T-cell groups, the responses were deeper and quicker by month one. And regarding the third question, if a soluble BCMA can predict an earlier response, we saw that patients that achieve at least partial response by month one decrease soluble BCMA levels around 40 points. But patients that do not achieve response, we have a very big increase of soluble BCMA levels. 

So we can conclude with this study that soluble BCMA is a serum biomarker that correlates with tumor burden markers, that can be a dynamic biomarker, and also can predict patients’ response. So we think that soluble BCMA, although further studies are needed, we think this is a strategy we can take into routine clinical practice.

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