SOHO 2026 | MonumenTAL-3: potential benefits and risks of adding pomalidomide to Tal-D in RRMM

So, in the MonumenTAL-3 study, we had as a control arm, daratumumab, pomalidomide and dex. And as experimental arms, we had two different treatments, a doublet, talquetamab plus Daratumumab, or a triplet, talquetamab, daratumumab, and pomalidomide. So, both experimental arms, Tal-Dara and Tal-Dara-POM, resulted in being superior in terms of responses, CR rates, MRD-negativity rates, eventually also progression-free survival, and numerically also overall survival as compared to DPd. And if we look at the data, we’ll see that two years of follow-up, roughly, we have a median progression-free survival for DPd of two years, which is, in fact, one of the longest, if not the longest, PFS shown in a study, in a large Phase III study by the control arm. And at the same time point, roughly 80% of patients treated with Tal-Dara or Tal-Dara-POM were free from progression and alive. So numerically, there is not much difference between the doublet and the triplet. So the addition of pomalidomide carried probably a little bit more in terms of progression-free survival, in terms of CR rates, but we are talking about very small numbers. So it’s unclear at this stage if in terms of efficacy, pomalidomide really added efficacy, let’s say. On the other hand, we have seen more infections and more neutropenia associated with the use of pomalidomide. And in fact, the combination of Tal-Dara alone carried a lower risk of infections, not only as compared to Tal-Dara-POM, but also as compared to the control arm. So clearly, there is an impact in terms of infections and neutropenia carried by the use of pomalidomide. So I would say that for sure, Tal-Dara is a very strong combination at first relapse in patients who have been exposed to Dara only or are naive to Dara for sure. The addition of pomalidomide is at this stage, it’s based on patient characteristics and the feeling that investigators may have about a more intensive treatment, which may down the road result into more sustained responses, longer PFS. But at this point, we haven’t seen this. We haven’t seen this yet. I would say that a possibility is also in clinical practice to start with the doublet and maybe add the pomalidomide for patients who are not responding optimally to the doublet. This is not supported by the study, but this is a consideration that can be made as an ongoing assessment and treatment adjusted.

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