MRD dynamics predicts progression and reveals a vulnerable state for immunotherapy interception in multiple myeloma.

MRD dynamics from ≥3 assessments in 539 newly diagnosed multiple myeloma patients identifies five MRD-behavior subgroups, with late-sustained response showing excellent survival and primarily/resurgent resistance showing dismal outcomes.

• Why it matters: Clinically meaningful use of more than two MRD timepoints is unclear, including how to stratify patients with ≥3 measurements and whether acting on persistent MRD could improve outcomes.
• What they did: MRD dynamics were computed using next-generation flow cytometry and CONNECTOR across 3610 MRD assessments in GEM2012MENOS65/GEM2014MAIN and GEM2017FIT, then validated in 249 routine-practice patients; anti-BCMA CAR T therapy was tested in MIcγ1hCRBN mice.
• The result: MRD dynamics outperformed transplant eligibility and the Revised International Staging System, and anti-BCMA CAR T infusion at MRD resistance prolonged mouse survival versus identical treatment at relapse, suggesting a vulnerable interception window.

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