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MRD-negative complete remission

MRD-negative complete remission means not just no leukaemia visible under the microscope, but none detectable with tests a thousand times more sensitive. It is the goal of modern leukaemia treatment.

Complete remission with undetectable measurable residual disease by flow (10^-4) or molecular methods (10^-5 to 10^-6). Prognostic across AML, ALL, CLL, and myeloma; accepted as a regulatory endpoint in ALL (blinatumomab MRD+ label) and, since FDA ODAC 2024, as an accelerated-approval endpoint in myeloma. Drives transplant decisions (AML), blinatumomab consolidation (ALL), and duration debates (CLL).

Endpoints: what this kind of term is about · animated schematic, not to scale
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Endpoints

Key papers

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rctNew England Journal of Medicine 2024changed practice
ECOG-ACRIN E1910: adding blinatumomab to chemotherapy for adults with B-cell ALL already in MRD-negative remission

E1910 changed the standard of care for adult B-ALL: immunotherapy is now part of front-line consolidation even for patients with no detectable leukaemia, because MRD-negative by flow cytometry does not mean cured. It also demonstrated that a T-cell engager can improve overall survival in a curative setting. Chemotherapy-light or chemotherapy-free regimens built on blinatumomab and inotuzumab are the next step.

translationalNature 2023changed practice
AUGMENT-101: revumenib, the first menin inhibitor, in relapsed leukaemias driven by KMT2A rearrangement or NPM1 mutation

Revumenib proved that a transcriptional dependency, rather than a kinase, can be drugged in leukaemia, opening treatment for two genetic subgroups that together cover roughly a third of AML plus most infant ALL. It is now approved and is being combined with venetoclax-azacitidine and intensive chemotherapy in front-line trials. Single-agent remissions are often short without transplant.

rctNew England Journal of Medicine 2020changed practice
VIALE-A: venetoclax plus azacitidine for older adults with acute myeloid leukaemia who cannot have intensive chemotherapy

VIALE-A turned a palliative regimen into one that produces remission in two-thirds of older AML patients and is now the reference treatment for anyone not fit for intensive chemotherapy. It shifted the field towards lower-intensity targeted combinations and opened the door to adding FLT3, IDH and menin inhibitors to the backbone. Cure remains uncommon and most patients relapse within two years.

translationalNew England Journal of Medicine 2014changed practice
Maude 2014: CD19 CAR-T cells produce complete remission in 27 of 30 children and adults with relapsed ALL

This paper is the proof-of-concept for a living drug: a single infusion of a patient's own engineered T cells could eradicate leukaemia that had survived chemotherapy, transplant and antibody therapy. It defined cytokine release syndrome and its antidote, tocilizumab, and revealed antigen-loss relapse. It led directly to the first approved gene-modified cell therapy three years later.

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