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IMS 2026 | Daratumumab- versus isatuximab-based regimens in newly diagnosed multiple myeloma
Heinz Ludwig, MD, Wilhelminen Cancer Research Institute, Vienna, Austria, discusses a systematic review and meta-analysis comparing daratumumab- and isatuximab-based regimens in newly diagnosed multiple myeloma. He highlights broadly similar progression-free survival (PFS) and overall efficacy, with small differences in response rates and grade 3 or higher infections, while emphasizing the heterogeneity of the available studies and the limitations of indirect comparisons. This interview took place at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, UK.
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Transcript
We have now two CD38 antibodies, but they bind to different epitopes of the CD38 molecule. So the question pops up whether they are comparable in their activity and side effects. As it is unrealistic that we will have a head-to-head randomized trial, we decided to do a meta-analysis and we included 15 eligible studies which used daratumumab or isatuximab combinations for first-line therapy. So first of all, I have to say a few caveats because the studies are very heterogeneous...
We have now two CD38 antibodies, but they bind to different epitopes of the CD38 molecule. So the question pops up whether they are comparable in their activity and side effects. As it is unrealistic that we will have a head-to-head randomized trial, we decided to do a meta-analysis and we included 15 eligible studies which used daratumumab or isatuximab combinations for first-line therapy. So first of all, I have to say a few caveats because the studies are very heterogeneous. But when we then did all the meta-analyses, two important questions or findings popped up. Daratumumab is slightly more or significantly more effective in terms of overall response rate, but the difference is relatively small, 94% versus 91% in overall response rate. Other differences of importance, of course, there’s a difference in MRD rate, but that is not significant, favoring isatuximab. But we have to be careful, so we cannot really rely on this data because they are too limited. But we also looked at, of course, PFS. And PFS is very strongly supported by the data. And actually, PFS is similar. So that’s the good news. When you look at MRD rates, they are slightly higher, but it’s not significant with daratumumab. And when you look at side effects, grade 3 and higher infections are less frequent with isatuximab. But in general, both drugs are really comparable for clinical practice, so I think one can use one or the other, depending on what’s available to you. Personally, I’m quite confident that the meta-analysis is very solid, but there’s a word of caution because there’s a big, significant heterogeneity between different studies. So we have to be careful in interpreting the results. You can interpret the results as explanatory, but I don’t think it will change the main message. Both drugs are comparable. There are slight differences in overall response rates, slight differences in grade 3 and higher infections, but more or less PFS is similar. So both are excellent drugs.
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