Hepcidin-DMT1 interaction and GPRC5D-targeting bispecific antibody for MM

In this week's episode, Blood editor Dr. Laura Michaelis interviews authors Drs. Marion Falabrègue and Ajai Chari on their papers published in volume 146 issue 24 of Blood. The work of Dr. Falabrègue and colleagues in "Intestinal hepcidin overexpression promotes iron deficiency anemia and counteracts iron overload via DMT1 downregulation" indicates that iron absorption from the apical surface of enterocytes can be modulated through manipulation of the hepcidin-DMT1 interaction, opening new avenues for research and therapeutic manipulation. "Talquetamab plus daratumumab in multiple myeloma" features a phase 1b/2 trial of 65 heavily pretreated patients with MM, where Chari et al combined daratumumab and talquetamab, a GPRC5D-targeting bispecific antibody, reporting depletion of CD38-expressing regulatory T cells following daratumumab and impressive efficacy, with an 80% overall (57% complete) response rate and median progression-free survival of 23.3 months. This regimen is now being evaluated in a phase 3 trial.