Patients with relapsed and/or refractory multiple myeloma whose disease has become refractory to both lenalidomide and daratumumab represent a distinct and clinically demanding sub-population. Standard options are narrowed because these patients have already progressed through two major drug classes.
This protocol specifically addresses multiple myeloma in the relapsed and/or refractory setting, in patients with disease refractory to lenalidomide and refractory to daratumumab. Selecting an appropriate next regimen requires evidence from trials that enrolled this prior-exposure population — a limited evidence base.
For patients in this situation, preferred strategies include a CAR-T cell therapy and an antibody-drug conjugate–based combination — the only approaches with trial evidence specifically in patients who have received both lenalidomide and daratumumab previously, in the early relapse setting. Further options exist for a subset of patients, subject to prior treatment sensitivity; their use is limited by scarce supporting evidence in this refractory population.
Full regimen selection, eligibility criteria, and sequencing are in the complete protocol below.
DOI: 10.1038/s41571-025-01041-x