Issues

Chimeric antigen receptor (CAR) T cells have been approved in myeloma as a late-line therapy. In this setting, their performance is likely suboptimal due to patients’ weakened immune systems, higher disease burden, and selection of multi-therapy resistance. There is hope that moving CAR T-cell treatment to a frontline setting may open a safer and more effective avenue of treatment. In this issue, Garfall and colleagues present pioneering work with a phase I clinical trial of dual-targeting CAR T cells as an early- versus late-line therapy supporting safety and feasibility of the treatment. At the same time, the lower-than-expected complete response rate suggests that patient-specific factors beyond those addressed by early-line use continue to shape the outcomes. The cover image by Tetiana Sichkarenko illustrates how an optimal path out of the woods is fraught with challenges unique to the nature of each setting and its explorer. For details, see the article on p. 118.