Dr Burke on MRD Testing in CLL and Myeloma

In this installment of Chief Insights in Oncology, John M. Burke, MD, co-editor in chief of Targeted Therapies in Oncology, discusses his column from the September II 2025 issue.

Burke discusses the underutilization of minimal residual disease (MRD) testing in treating hematological malignancies, despite its availability. The main reason cited for this is that doctors don't know what to do with the information, as the results have traditionally been considered prognostic rather than a guide for patient management. This perspective, however, may be changing due to 2 recent studies published in The New England Journal of Medicine.

The first study, the MIDAS trial, focused on multiple myeloma. It compared a quadruplet drug regimen (isatuximab, carfilzomib, lenalidomide, and dexamethasone) with and without an autologous stem cell transplant (ASCT). The results showed that patients who received the quadruplet regimen alone achieved an undetectable MRD rate of 84%, which was very similar to the 86% rate seen in patients who also underwent an ASCT. This suggests that ASCT may not be necessary for patients who achieve undetectable MRD after induction therapy with this quadruplet regimen, potentially allowing for the omission of a costly and intensive procedure.

The second study, the FLAIR trial, examined chronic lymphocytic leukemia (CLL). In this trial, a doublet of ibrutinib and venetoclax was compared to single-agent ibrutinib. The doublet significantly improved both progression-free survival and overall survival. Approximately half of the patients on the doublet achieved undetectable MRD after 1 year. This is the first time a frontline CLL treatment has shown a survival advantage over a single-agent BTK inhibitor. The findings suggest that MRD testing could be used to determine the optimal duration of therapy with the doublet regimen, moving MRD testing from a prognostic tool to one that can directly influence patient care.

Read Dr Burke's full column here.