EHA 2026 | Findings from MonumenTAL-3: Tal+Dara±Pom versus Dara+Pom+Dex in R/R multiple myeloma

We looked at the bispecific antibody talquetamab which is currently approved for heavily pretreated patients, for myeloma patients who’ve relapsed just one or more times. So we looked at talquetamab in combination with the CD38 antibody daratumumab, with or without the immunomodulatory drug pomalidomide. And we compared those two experimental arms with a standard of care in the early relapse space, which is daratumumab with pomalidomide and dexamethasone. The primary endpoint of our study was progression-free survival. Secondary endpoints included response rate, depth of response, overall survival and safety. And what we were able to show in this group of patients is that talquetamab with daratumumab, with or without pomalidomide, reduced the risk of disease progression or death in both of the arms and also reduced the risk of death from any cause. So we improved both progression-free and overall survival. And when we looked at the progression-free survival benefit across clinically relevant subgroups, we saw consistent benefits, including in older patients, patients who have ISS stage 3 disease, soft tissue plasmacytomas, high-risk cytogenetics, patients who’ve previously been exposed to daratumumab, consistent progression-free survival benefits. Now, with regards to side effects, we saw less infection with the talquetamab daratumumab arm compared to BCMA targeted bispecific antibodies that are currently available. So for example, the grade three and four infection signal with talquetamab and daratumumab was 29% in contrast to 54% that we saw in the MajesTEC-3 study with daratumumab combined with teclistamab. We also saw less neutropenia in that particular scenario as well with the talquetamab and the daratumumab. But the target of talquetamab, GPRC5D, is expressed in select epithelial structures in the skin as well as the nail beds, mouth, and to some extent, the inferior olivary nucleus of the cerebellum, which leads to a very distinct side effect profile, this particular agent. So we saw taste changes that in some instances led to weight loss, but in most cases, not severe weight loss. We saw skin side effects that are manageable with topical steroid therapies. We saw nail changes. Importantly, the skin and nail changes that we saw were typically low to moderate in severity and rarely grade three. We did see some signal of cerebellar side effects. So about 12.5% to 14.5% of patients had either ataxia or some form of balance disorder. But thankfully, only 2.2% to 2.9% of patients had a grade 3 event. So I think on balance, when you look at the risk and the benefit and the notable progression-free and overall survival advantage, I think that supports talquetamab and daratumumab with or without pomalidomide as a new standard of care for relapsed myeloma patients as early as first relapse.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.