Skip to content
MRD Watch

Sunday, November 15, 2026

Subscribe
Sponsor this briefing. One site and newsletter slot, $250/week.

MRD evidence

What the studies show

Landmark papers an MRD reader should know, including trials that did not meet their aim. Numbers below are taken from the abstracts. Assay names are labels, not a ranking. The full list remains on Research. Multi-cancer early detection is on MCED.

Level 1

A prospective trial in which the ctDNA or MRD result assigns, withholds, or changes treatment. Randomized and single-arm adaptive trials both qualify. Positive and negative trials are listed.

Level 2

A large prospective observational cohort, or a correlative analysis from a phase 3 trial or other large study. The test informs prognosis or describes a treatment association. It does not assign therapy.

Level 3

A smaller cohort, a single-center series, a feasibility study, or an analytical validation. Useful for methods and early signals, not for changing practice on its own.

Must-know papers

  1. PositiveLevel 12025 · The New England Journal of Medicine

    ctDNA-Guided Adjuvant Atezolizumab in Muscle-Invasive Bladder Cancer.

    Powles T, et al. PMID 41124204. doi 10.1056/NEJMoa2511885

    Phase 3 trial. 761 people with muscle-invasive bladder cancer were monitored with ctDNA after surgery; 250 who tested positive were randomized 2:1 to atezolizumab or placebo. Median disease-free survival was 9.9 versus 4.8 months (HR 0.64) and median overall survival was 32.8 versus 21.1 months (HR 0.59). People who stayed ctDNA-negative were not treated on study.

  2. PositiveLevel 22021 · Nature

    ctDNA guiding adjuvant immunotherapy in urothelial carcinoma.

    Powles T, et al. PMID 34135506. doi 10.1038/s41586-021-03642-9

    Correlative analysis of a phase 3 adjuvant trial (IMvigor010) that missed its primary endpoint in all randomized patients. Among 581 people evaluable for ctDNA, 214 (37%) were positive and had a poor prognosis on observation (HR 6.3). In the ctDNA-positive group, atezolizumab improved disease-free survival (HR 0.58) and overall survival (HR 0.59). No treatment difference was seen in the ctDNA-negative group.

  3. PositiveLevel 22024 · European Urology

    Updated Overall Survival by Circulating Tumor DNA Status from the Phase 3 IMvigor010 Trial: Adjuvant Atezolizumab Versus Observation in Muscle-invasive Urothelial Carcinoma.

    Powles T, et al. PMID 37500339. doi 10.1016/j.eururo.2023.06.007

    Updated overall-survival analysis of IMvigor010 by ctDNA status. The abstract reports an overall-survival benefit for adjuvant atezolizumab versus observation in people who were ctDNA-positive.

  4. PositiveLevel 22026 · Annals of Oncology

    Adjuvant nivolumab versus placebo for high-risk muscle-invasive urothelial carcinoma: 5-year efficacy and ctDNA results from CheckMate 274.

    Galsky MD, et al. PMID 41110694. doi 10.1016/j.annonc.2025.09.139

    Five-year update of CheckMate 274. Among 709 people with high-risk muscle-invasive urothelial carcinoma, adjuvant nivolumab improved disease-free survival versus placebo (HR 0.74). In a post hoc Signatera analysis, the disease-free survival HR was 0.35 when baseline ctDNA was detectable and 0.99 when it was not.

  5. PositiveLevel 22024 · JCO Precision Oncology

    Longitudinal Testing of Circulating Tumor DNA in Patients With Metastatic Renal Cell Carcinoma.

    Basu A, et al. Alan Tan is the senior author. PMID 39693589. doi 10.1200/PO-24-00667

    Retrospective series, Alan Tan senior author. In 92 people with metastatic renal cell carcinoma tested with Signatera, serial ctDNA negativity or clearance tracked with longer progression-free survival, and longitudinal positivity during surveillance tracked with shorter progression-free survival.

  6. PositiveLevel 12022 · The New England Journal of Medicine

    Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer.

    Tie J, et al. PMID 35657320. doi 10.1056/NEJMoa2200075

    DYNAMIC, a randomized trial in stage II colon cancer. Of 455 people, 302 had ctDNA-guided management and 153 had standard management. Adjuvant chemotherapy use was 15% versus 28%. Two-year recurrence-free survival was 93.5% versus 92.4%, meeting the non-inferiority margin.

  7. NegativeLevel 12025 · Nature Medicine

    Circulating tumor DNA-guided adjuvant therapy in locally advanced colon cancer: the randomized phase 2/3 DYNAMIC-III trial.

    Tie J, et al. PMID 41115959. doi 10.1038/s41591-025-04030-w

    DYNAMIC-III, a randomized phase 2/3 trial in stage III colon cancer. Of 968 evaluable people, 702 (72.5%) were ctDNA-negative. Three-year recurrence-free survival was 87% if ctDNA-negative and 49% if positive. De-escalation in the negative group did not meet non-inferiority (85.3% versus 88.1%). Escalation in the positive group did not improve 2-year recurrence-free survival (51% versus 61%).

  8. PositiveLevel 22023 · Nature Medicine

    Molecular residual disease and efficacy of adjuvant chemotherapy in patients with colorectal cancer.

    Kotani D, et al. PMID 36646802. doi 10.1038/s41591-022-02115-4

    GALAXY, the observational arm of CIRCULATE-Japan, in 1,039 people with stage II–IV resectable colorectal cancer. Postsurgical ctDNA positivity at 4 weeks was associated with recurrence (HR 10.0) and was the strongest prognostic factor in stage II or III disease (HR 10.82).

  9. PositiveLevel 22022 · Clinical Cancer Research

    Circulating Tumor DNA in Stage III Colorectal Cancer, beyond Minimal Residual Disease Detection, toward Assessment of Adjuvant Therapy Efficacy and Clinical Behavior.

    Henriksen TV, et al. PMID 34625408. doi 10.1158/1078-0432.CCR-21-2404

    Prospective series of 168 people with stage III colorectal cancer (1,204 plasma samples; Reinert is an author). Postoperative ctDNA detection predicted recurrence (HR 7.0). The assay used 16 patient-specific variants.

  10. PositiveLevel 22026 · NPJ Precision Oncology

    Validation of a methylation-based, tissue-free MRD assay in colorectal cancer patients from the GALAXY study.

    Nakamura Y, et al. PMID 41555007. doi 10.1038/s41698-026-01277-5

    A tissue-free methylation assay (Latitude) was tested on 1,230 time points from 195 people in GALAXY. ctDNA positivity was associated with worse disease-free survival in the residual-disease window (HR 10.0) and in surveillance (HR 31.9).

  11. NegativeLevel 12026 · Nature Medicine

    Post-adjuvant chemotherapy in ctDNA-positive patients with resected colorectal cancer: a randomized phase 3 trial.

    Bando H, et al. PMID 42260101. doi 10.1038/s41591-026-04428-0

    ALTAIR, a randomized phase 3 trial (NCT04457297). 243 people with resected colorectal cancer who were ctDNA-positive without radiographic disease were assigned to trifluridine/tipiracil or placebo. Median disease-free survival was 9.30 versus 5.55 months (HR 0.79, P = 0.107). The primary endpoint was not met.

  12. NegativeLevel 12026 · Nature Cancer

    Circulating tumor DNA-guided de-escalation or escalation of adjuvant therapy in high-risk stage II and stage III colon cancer: the phase 2 PEGASUS trial.

    Marsoni S, et al. PMID 42736431. doi 10.1038/s43018-026-01237-9

    PEGASUS, a phase 2 ctDNA-guided trial. Of 135 people, 35 (26%) were ctDNA-positive after surgery. The primary endpoint, a 2-year relapse-free rate of at least 92% in the ctDNA-negative group, was not met (observed 88%).

  13. PositiveLevel 32015 · Science Translational Medicine

    Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer.

    Garcia-Murillas I, et al. PMID 26311728. doi 10.1126/scitranslmed.aab0021

    Prospective cohort of 55 people with early breast cancer. ctDNA after apparently curative treatment predicted metastatic relapse (HR 25.1 at one postsurgical time point). Serial samples gave a median lead time of 7.9 months. The cohort is small, so this is Level 3 even though it is a landmark methods paper.

  14. NegativeLevel 12023 · Annals of Oncology

    Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate- and high-risk early-stage triple-negative breast cancer.

    Turner NC, et al. PMID 36423745. doi 10.1016/j.annonc.2022.11.005

    c-TRAK TN, a phase 2 trial (NCT03145961). ctDNA was detected by 12 months in 44 of 161 people (27.3%). Of those allocated to pembrolizumab, 23 of 32 already had metastases on staging, and none of the five who started pembrolizumab had sustained ctDNA clearance.

  15. PositiveLevel 22026 · Clinical Cancer Research

    Longitudinal ctDNA Monitoring for Postsurgical Disease Surveillance in Patients with Stage I to IIIB Melanoma.

    Ansstas G, et al. Alan Tan is the senior author. PMID 41632449. doi 10.1158/1078-0432.CCR-25-3643

    Retrospective real-world series, Alan Tan senior author. In 190 people with stage I to IIIB melanoma, any postoperative ctDNA detection on a tumor-informed 16-plex assay was associated with shorter recurrence-free survival (HR 40.63).

  16. PositiveLevel 22023 · Nature

    Tracking early lung cancer metastatic dissemination in TRACERx using ctDNA.

    Abbosh C, et al. PMID 37055640. doi 10.1038/s41586-023-05776-4

    TRACERx developed ctDNA assays tracking a median of 200 mutations from resected non-small cell lung cancer, using longitudinal plasma to study early metastatic spread. This is a cohort methods and biology paper, not a treatment-assignment trial.

  17. PositiveLevel 22025 · Cell

    Longitudinal ultrasensitive ctDNA monitoring for high-resolution lung cancer risk prediction.

    Black JRM, et al. PMID 41205598. doi 10.1016/j.cell.2025.10.020

    TRACERx analysis of 2,994 plasma samples from 431 people with non-small cell lung cancer. A whole-genome tumor-informed assay tracking 1,800 variants found that detection below 80 parts per million, before or after surgery, was prognostic.

  18. PositiveLevel 22025 · Nature Medicine

    Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

    Black JRM, et al. PMID 39806071. doi 10.1038/s41591-024-03216-y

    TRACERx preoperative analysis using NeXT Personal in 171 people with early-stage lung cancer. ctDNA was detected before surgery in 81% of those with lung adenocarcinoma.

  19. PositiveLevel 22019 · Clinical Cancer Research

    Rapid Clearance Profile of Plasma Circulating Tumor HPV Type 16 DNA during Chemoradiotherapy Correlates with Disease Control in HPV-Associated Oropharyngeal Cancer.

    Chera BS, et al. PMID 31088830. doi 10.1158/1078-0432.CCR-19-0211

    Prospective biomarker trial in 103 people with p16-positive oropharyngeal cancer treated with definitive chemoradiotherapy. A rapid clearance profile of plasma HPV type 16 DNA correlated with disease control.

  20. PositiveLevel 22020 · Journal of Clinical Oncology

    Plasma Circulating Tumor HPV DNA for the Surveillance of Cancer Recurrence in HPV-Associated Oropharyngeal Cancer.

    Chera BS, et al. PMID 32017652. doi 10.1200/JCO.19.02444

    Prospective surveillance trial. Longitudinal plasma circulating tumor HPV DNA detected clinical recurrence in nonmetastatic HPV-associated oropharyngeal cancer.

  21. PositiveLevel 22025 · Annals of Oncology

    Ultrasensitive detection and tracking of circulating tumor DNA to predict relapse and survival in patients with locally advanced cervical cancer: phase III CALLA trial analyses.

    Mayadev J, et al. PMID 40500687. doi 10.1016/j.annonc.2025.05.533

    In a pre-planned CALLA correlative analysis, Personalis NeXT Personal detected ctDNA in 183/185 (98.9%) baseline samples; post-CRT (C3D1) ctDNA detection preceded clinical progression by a median of 164 days (95% CI 85–250), and lower-than-median baseline ctDNA was associated with better PFS in the CRT arm (HR 0.49, 95% CI 0.26–0.95).

  22. Neutral or mixedLevel 12023 · The Lancet Haematology

    Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial.

    Costa LJ, et al. PMID 37776872. doi 10.1016/S2352-3026(23)00236-3

    Final report of the single-arm phase 2 MASTER trial. Next-generation sequencing measurable residual disease was used to shorten or stop daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed myeloma. This is treatment guided by bone-marrow MRD, not by ctDNA.

  23. Neutral or mixedLevel 32020 · BMC Cancer

    Analytical evaluation of the clonoSEQ Assay for establishing measurable residual disease in acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma.

    Ching T, et al. PMID 32605647. doi 10.1186/s12885-020-07077-9

    Analytical validation of the clonoSEQ sequencing assay for measurable residual disease in acute lymphoblastic leukemia, chronic lymphocytic leukemia, and multiple myeloma. It reports laboratory performance, not a treatment trial.

Urine tumor DNA studies

From the utDNA catalog. Plasma ctDNA studies are labeled plasma. Conference abstracts stay labeled as abstracts. These figures are not a ranking.

  1. Peer-reviewed

    Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA.

    Dudley JC, Schroers-Martin J, Lazzareschi DV, Shi WY, Chen SB, Esfahani MS, Trivedi D, Chabon JJ, Chaudhuri AA, et al.; Alizadeh AA and Diehn M senior.

    Cancer Discov 2019.

    n: 67 healthy adults and 118 patients with early-stage bladder cancer

    Pretreatment or surveillance, early-stage BLCA

    Assay: uCAPP-Seq (utDNA CAPP-Seq), targeted high-throughput sequencing

    • Median 6 mutations per patient; PLEKHS1 promoter mutations in 46%.
    • Pretreatment detection 93% tumor-informed, 84% tumor-naive, 96% to 100% specificity.
    • Surveillance: utDNA detected in 91% of patients who ultimately recurred; preceded clinical progression in 92% (median lead time 2.7 months in the full text).
    • Outperformed UroVysion (P=0.02) and cytology and cystoscopy combined (P<=0.006); detected 100% of cytology-positive cases and 82% that cytology missed (abstract).
    • Surveillance subset in full text: tumor-naive profiling detected 100% of recurrent cases with positive cytology (n=14) and 73.9% with negative cytology (n=23).

  2. Peer-reviewed

    Urine cell-free RNA for bladder cancer detection and treatment response prediction.

    Liu KJ, Shi WY, Nesselbush MC, Phillips NA, Mach KE, et al.; Alizadeh AA, Liao JC, and Diehn M senior.

    Nat Med. Published 2 October 2026. Open access on the Nature page.

    n: 683 urine samples from patients with cancer and controls

    Detection, MRD, and BCG-versus-chemotherapy response prediction in bladder cancer; also transcripts from prostate and kidney cancers noted.

    Assay: uRARE-seq (urine random priming and affinity capture of cell-free RNA fragments for enrichment analysis by sequencing)

    • 95% sensitivity at 90% specificity for detecting localized bladder cancer.
    • Outperformed urine tumor DNA analysis and was unaffected by field-effect mutations.
    • Sensitively detected MRD and distinguished complete molecular responses after surgery from those after BCG.
    • Pretreatment urine from BCG complete responders enriched for T-cell and other immune signatures; nonresponders showed higher proliferation-related gene expression.
    • In pretreatment urine from 114 patients, a biomarker predicting BCG versus chemotherapy response had AUC 0.93 and was strongly associated with recurrence risk.
    • Authors state prospective studies are needed to assess clinical utility.

  3. Peer-reviewed

    Field-effect-informed urine liquid biopsy for bladder cancer.

    Shi WY, Liu KJ, Esfahani MS, Mach KE et al. Cell 2026;189(4):1024-1038.e9.

    n: 261 serial specimens from 61 NMIBC patients (validation); plus training and control analyses described in field_cancerization

    Intermediate- or high-risk NMIBC, TURBT and adjuvant BCG

    Assay: Field-effect-informed (RePhyNERX-enhanced) uCAPP-Seq, tumor-informed

  4. Peer-reviewed

    clinical trial (not utDNA; context)

    Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.

    Powles T, Catto JWF, Galsky MD, et al., including van der Heijden MS, NIAGARA Investigators.

    N Engl J Med 2024;391(19):1773-1786.

    n: 1063 (533 durvalumab, 530 comparison)

    Phase 3, cisplatin-eligible MIBC

    Assay: n/a (clinical end points)

    • 24-month EFS 67.8% vs 59.8%, HR 0.68 (0.56-0.82), P<0.001.
    • 24-month OS 82.2% vs 75.2%, HR 0.75 (0.59-0.93), P=0.01.

    co-author

  5. Conference abstract

    plasma ctDNA (not utDNA)

    Circulating tumor DNA (ctDNA) in patients with MIBC who received perioperative durvalumab in NIAGARA.

    J Clin Oncol 2025;43(16_suppl):4503.

    n: BEP 462 of 1063 (237 D, 225 C)

    Exploratory plasma ctDNA in NIAGARA

    Assay: Signatera, tumor-informed (Natera)

    • Baseline ctDNA+ 57% (260/460), pre-RC 22% (94/422).
    • Clearance baseline to pre-RC: 41% durvalumab vs 31% comparator.
    • Non-pCR 97% (86/89) if pre-RC ctDNA+.
    • Post-RC ctDNA+ 9% (31/345).
    • EFS benefit of durvalumab reported in both baseline ctDNA+ and ctDNA- groups.

  6. Conference abstract

    utDNA and plasma ctDNA

    Urinary tumor DNA (utDNA) and circulating tumor DNA (ctDNA) in patients with MIBC who received perioperative durvalumab in NIAGARA.

    J Clin Oncol 2026;44(7_suppl):636. ASCO GU 2026. Conference abstract; not a full paper.

    n: BEP 265 of 1063 (25%; 134 D, 131 C); utDNA at BL n=205, pre-RC n=183

    Exploratory utDNA + ctDNA in NIAGARA, cisplatin-eligible MIBC, pre-cystectomy

    Assay: Personalized Signatera (Natera), same framework as the plasma test

    • Lower baseline utDNA associated with longer EFS (low vs high HR 0.65, 95% CI 0.40-1.04).
    • utDNA+ rate 85% at baseline, 55% pre-RC.
    • utDNA clearance associated with longer EFS (HR 0.24, 95% CI 0.09-0.62); clearance 39% vs 27% (12 points higher with durvalumab).
    • Pre-RC utDNA-: pCR 72% (55/76) vs 18% (17/96) if utDNA+.
    • utDNA+ correlated with noninvasive residual disease (<T2N0M0); ctDNA+ with invasive disease or N+/M+.
    • 24-month EFS: dual-negative 90% (83-97), utDNA+ only 75% (65-87), dual-positive 55% (41-75).

    Conference abstract, exploratory, 25% of ITT. Full paper not found in PubMed.

    UroToday interview, Michiel van der Heijden. Interview commentary (e.g. plasma thresholds used for urine) is not a paper result.

  7. Peer-reviewed

    utDNA and plasma ctDNA MRD (exploratory) plus clinical end points

    Gemcitabine Intravesical System Plus Cetrelimab or Cetrelimab Alone as Neoadjuvant Therapy in Muscle-Invasive Bladder Cancer: SunRISe-4 Primary Analysis and Biomarker Results.

    Necchi A, Guerrero-Ramos F, Crispen PL, Herrera-Imbroda B, Garje R, Szabados B, Peyton CC, Pradere B, Ku JH, Shore N, Bogemann M, Preston MA, Xylinas E, Sanchez de Llano C, Gong C, Hasan M, Urtishak K, Battaglia S, Stitou H, Bhanvadia S, Sweiti H, Psutka SP (22 authors on PubMed; Galsky MD is not on this list).

    J Clin Oncol 2026;44(7):586-597. Published 3 December 2025.

    n: 159 treated; 88 cohort 1 and 46 cohort 2 underwent RC; utDNA available 67 at baseline, 65 at week 12

    Phase 2, cisplatin-ineligible or -refusing cT2-T4a N0M0 MIBC planned for RC; 5:3 randomization, cohort 1 TAR-200 + cetrelimab, cohort 2 cetrelimab alone. Data cutoff 9 May 2025.

    Assay: utDNA and ctDNA MRD; vendor and gene content not named in the abstract (vendor and gene content are not named in the abstract).

    • pCR, pOR (<=ypT1N0), 1-year RFS: 38%, 53%, 77% in cohort 1 vs 28%, 44%, 64% in cohort 2.
    • Baseline utDNA+ 55/67 (82.1%); week 12 utDNA+ 34/65 (52.3%).
    • Week-12 utDNA- and clearance correlated with pCR (P<10^-5 and P<10^-3 in abstract; Fisher P=5.4e-6 for week-12 status in results text).
    • 22/27 (81.5%) who achieved pCR were utDNA- at week 12 vs 7/33 (21.2%) who did not. ROC 0.80 (0.70-0.90); NPV 0.81.
    • Clearance in 14/30 (46.7%) with available data (7/18 C1, 7/12 C2). 12/15 (80.0%) baseline+ with pCR had clearance vs 2/15 (13.3%) without pCR.
    • ctDNA- at baseline and week 12 associated with longer RFS (P=0.04 and 0.01).
    • Authors: utDNA and ctDNA support further investigation as biomarkers for residual local and nonlocal disease, respectively.

    Not on the PubMed author list of this JCO paper. Galsky's own utDNA work is the HCRN GU16-257 PNAS 2026 paper.

  8. Peer-reviewed

    clinical (utDNA not in main abstract)

    TAR-200 for BCG-Unresponsive High-Risk NMIBC: Results From the Phase IIb SunRISe-1 Study.

    Daneshmand S, Van der Heijden MS, Jacob JM, et al., including Necchi A.

    J Clin Oncol 2025;43(33):3578-3588.

    • The main paper’s abstract does not report utDNA. Complete numeric utDNA results from ESMO 2025 abstract 3088P were not extracted from the primary abstract, so those rates are not shown.

    ESMO 2025 abstract 3088P (Ann Oncol, S0923-7534(25)04622-8) and a J&J Medical Connect congress PDF address molecular markers including baseline urinary tumor DNA MRD. Complete numeric utDNA results were not independently extracted from the primary abstract. Rates from that abstract are not included.

  9. Peer-reviewed

    clinical outcomes in FGFR3/2-altered NMIBC; utDNA/urine FGFR monitoring not in final abstract

    Erdafitinib in Patients with High- and Intermediate-risk Non-muscle-invasive Bladder Cancer: Final Analysis of THOR-2 Study.

    Daneshmand S, Zaucha R, Catto JWF, Tran B, Master V, Lotan Y, et al., including Maranchie JK.

    Eur Urol 2026;89(2):165-173.

    • Cohort 1 (HR papillary, prior BCG), n=73, 2:1 erdafitinib vs intravesical chemo: median RFS NR (28.6 mo-NE) vs 11.6 mo, HR 0.28 (0.13-0.61), nominal P=0.0007.
    • Cohort 2 (CIS +/- papillary), n=16: CR 94% at 8 weeks, 81% at 32 weeks; mDoR 23.3 months.
    • Cohort 3 (IR), n=18: CR 89%.

    A urine FGFR or utDNA monitoring analysis is not described in the final-paper abstract. How FGFR3/2 alterations were ascertained (tissue vs urine) is not stated in that abstract.

  10. Peer-reviewed

    plasma tumor-informed ctDNA (NOT utDNA)

    ctDNA-guided immunotherapy following radical cystectomy for muscle-invasive bladder cancer: results from the TOMBOLA trial.

    Dyrskjot L, Birkenkamp-Demtroder K, Nordentoft I, et al., including Jensen JB.

    Ann Oncol 2026;37(5):712-724.

    n: 192 enrolled, 178 assessable, median FU 34 months

    Danish multicenter, open-label, single-arm phase 2. MIBC after NAC and RC. ctDNA+ started atezolizumab up to 1 year; ctDNA- received IO only if imaging showed metastases.

    Assay: Serial tumor-informed plasma ctDNA (not utDNA)

    • 104 (58%) ctDNA+ within 2 years after RC, 63% of those within 4 months.
    • Median lead time ctDNA to imaging-confirmed recurrence: 90 days (range -61 to 961).
    • 60% (50/84) of ctDNA+ patients who completed atezo with scans/ctDNA for the primary end point achieved complete molecular and radiographic response.
    • 1-year RFS 97% if ctDNA- vs 76% if ctDNA+.

  11. Peer-reviewed

    plasma ctDNA (NOT utDNA)

    Early Detection of Metastatic Relapse and Monitoring of Therapeutic Efficacy by Ultra-Deep Sequencing of Plasma Cell-Free DNA in Patients With Urothelial Bladder Carcinoma.

    Christensen E, Birkenkamp-Demtroder K, Sethi H, et al., including Dyrskjot L.

    J Clin Oncol 2019;37(18):1547-1557.

    n: 68 patients, 656 plasma samples

    Assay: Tumor-informed ultra-deep sequencing (median 105,000x)

    • ctDNA at diagnosis HR 29.1, P=0.001.
    • After cystectomy, ctDNA identified metastatic relapse with 100% sensitivity and 98% specificity; median lead time 96 days.
    • ctDNA dynamics during chemo associated with recurrence (P=0.023); pathologic downstaging was not.

  12. Peer-reviewed

    utDNA

    Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study.

    Chauhan PS, Chen K, Babbra RK, et al., including Smith ZL, Arora VK, Chaudhuri AA.

    PLoS Med 2021;18(8):e1003732.

    n: 42 localized bladder cancer (32 MIBC, 19 of those with NAC) and 15 healthy adults

    Urine on the day of curative-intent RC

    Assay: uCAPP-Seq, tumor-naive (Diehn-group method; WashU / Chaudhuri lab, not a Diehn-lab paper)

    • Median utDNA 0% healthy vs 2.4% patients; 4.3% if residual disease (n=16) vs 0% if pCR (n=26), P=0.002.
    • utDNA MRD vs absence of pCR: sensitivity 81%, specificity 81%; LOO accuracy 81% (P=0.007).
    • PFS HR 7.4 (1.4-38.9), P=0.02.
    • Mutation concordance with tumor in 5 patients: 85%.

  13. Peer-reviewed

    utDNA multi-omics

    Urine cell-free DNA multi-omics to detect MRD and predict survival in bladder cancer patients.

    Chauhan PS, Shiang A, Alahi I, et al., including Chaudhuri AA.

    NPJ Precis Oncol 2023;7(1):6.

    n: 74

    Localized bladder cancer

    Assay: ULP-WGS plus uCAPP-Seq

    • Random-forest LOOCV 87% sensitive for residual disease vs surgical pathology.
    • PFS HR 3.00, P=0.01; OS HR 4.81, P=0.009.
    • Urine metrics predicted pCR 'far better than plasma ctDNA was able to.'

  14. Peer-reviewed

    clinical bladder-sparing (context for utDNA follow-up)

    Gemcitabine and cisplatin plus nivolumab as organ-sparing treatment for muscle-invasive bladder cancer: a phase 2 trial.

    Galsky MD, Daneshmand S, Izadmehr S, et al.

    Nat Med 2023;29(11):2825-2834.

    n: 76

    • cCR 43% (33/76, 95% CI 32-55%); 32 of 33 with cCR opted to forgo immediate cystectomy; PPV of cCR 0.97 (0.91-1).

  15. Peer-reviewed

    plasma ctDNA and utDNA

    Monitoring of plasma and urine tumor-derived DNA to inform bladder-sparing approaches for patients with muscle-invasive bladder cancer.

    Galsky MD, Izadmehr S, Yu M, Curtis SD, Douville C, et al., including Bettegowda, Kinzler, Papadopoulos, Vogelstein, Wang Y.

    Proc Natl Acad Sci USA 2026;123(8):e2533449123.

    Exploratory liquid biopsy in the gem/cis/nivo bladder-sparing trial; tumor-informed academic assay; authors note relatively small sample.

    Assay: Tumor-informed academic ctDNA and utDNA assay

    • 3-year bladder-intact survival among cCR after four rounds of systemic therapy: 69%.
    • Metastatic risk if pretreatment ctDNA detectable vs undetectable: HR 4.68 (1.10-43.35), P=0.036.
    • Only 4.5% (1 of 22) with undetectable baseline ctDNA developed metastatic disease.
    • utDNA more sensitive than plasma ctDNA for residual disease in the bladder.
    • Detectable utDNA in patients with cCR associated with shorter bladder-intact survival, HR 6.47 (1.34-31.31), P=0.008.

    first author — this is the Galsky utDNA study

  16. Peer-reviewed

    tissue/immune biomarkers; utDNA not in abstract

    Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial.

    Powles T, Kockx M, Rodriguez-Vida A, et al.

    Nat Med 2019.

    n: 95

    • pCR 31% (95% CI 21-41%). Biomarkers are tissue and immune contexture; utDNA is not reported in the abstract.

  17. Peer-reviewed

    urine DNA (mutations + aneuploidy)

    Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy.

    Springer SU, Chen CH, Rodriguez Pena MDC, et al., including Papadopoulos, Kinzler, Vogelstein, Netto.

    eLife 2018;7:e32143.

    n: 570 at risk for BC; 56 UTUC; surveillance subset

    Assay: UroSEEK: 11 genes plus copy-number changes on 39 chromosome arms

    • Positive in 83% of those who developed BC; combined with cytology, 95%.
    • UTUC: 75% of 56 positive (79% of non-invasive tumors).
    • Surveillance: genetic abnormalities in 68% of urines from patients with clinical recurrence.
    • Low-grade BC: UroSEEK 67%, cytology 0%.

  18. Peer-reviewed

    urine DNA methylation

    Urine DNA methylation assay enables early detection and recurrence monitoring for bladder cancer.

    Chen X, Zhang J, Ruan W, et al.

    J Clin Invest 2020;130(12):6278-6289. utMeMA.

    n: Model built in 313; prospective multicenter validation 175

    • 2-marker model: accuracy 86.7%, sensitivity 90.0%, specificity 83.1%.
    • Early-stage Ta and low-grade: sensitivity 64.5% vs cytology 11.8% and FISH 15.8%.

  19. Peer-reviewed

    multitarget urine tumor DNA (mutations + methylation)

    Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial.

    Wu J, Lin Y, Yang K, et al.

    Mol Cancer 2024;23(1):57. UI-Seek.

    n: Development 382; prospective validation 947 (ChiCTR2300076543)

    Assay: FGFR3 and TERT mutations plus ONECUT2 and VIM methylation

    • Sensitivity 91.37%, specificity 95.09%.
    • 75.81% for low-grade Ta; >93% for high-grade Ta and higher stages; >90% for both bladder and upper-tract tumors.
    • Post-surgery UC-score decreased in 97.7% (43/44).

  20. Peer-reviewed

    utDNA methylation (BladMetrix)

    Distinct longitudinal patterns of urine tumor DNA in patients undergoing surveillance for bladder cancer.

    Vedeld HM, et al.

    Mol Oncol 2024;18(11):2684-2695.

    n: 47 patients, 2-year surveillance

    • Detected 21/23 recurrences (91%): 5/5 T1, T2, and CIS (100%) and 10/12 Ta (83%); <1% false-negative tests.
    • Authors estimate a potential 55% reduction in cystoscopies, benefiting 79% of patients (estimate from the paper, not a randomized result).
    • 11/23 recurrences (48%) detected earlier with utDNA than cystoscopy.
    • Residual-utDNA patterns interpreted as MRD in 6% and field effect in 15%.

  21. Peer-reviewed

    urinary tumor-derived DNA plus multi-omics

    Elevated T-cell Exhaustion and Urinary Tumor DNA Levels Are Associated with BCG Failure in Patients with NMIBC.

    Strandgaard T, Lindskrog SV, Nordentoft I, Christensen E, Birkenkamp-Demtroder K, et al., including Jensen JB, Dyrskjot L.

    Eur Urol 2022;82(6):646-656.

    n: 156 BCG-treated NMIBC; urine tdDNA n=187 samples

    • Absence of post-BCG tdDNA clearance identified patients at high risk of recurrence (P=0.018).
    • Post-BCG HG recurrence associated with T-cell exhaustion (P=0.002).

  22. Peer-reviewed

    utDNA (UroAmp)

    Urine Tumor DNA to Stratify the Risk of Recurrence in Patients Treated with Atezolizumab for BCG-unresponsive NMIBC.

    St-Laurent MP, Singh P, McConkey DJ, et al., including Lerner SP, Black PC.

    Eur Urol 2025;88(5):430-434. SWOG S1605.

    n: UroAmp at baseline n=89 and 3 months n=77

    Assay: UroAmp

    • CR at 6 months: 13% of UroAmp+ vs 71% of UroAmp- at baseline (P<0.001).
    • 18-month EFS 23% vs 51% (HR 2.8, P<0.001).
    • Among 51 with no clinical evidence of disease at 3 months: 18-month EFS 38% if UroAmp+ vs 86% if negative (HR 3.5, P=0.01).

  23. Peer-reviewed

    utDNA

    Postinduction Urine Tumor DNA Is Predictive for Response to Maintenance Intravesical Therapy in NMIBC.

    Lotan Y, Korman H, Gadzinski A, et al.

    Eur Urol Oncol 2026. INSITE, observational.

    n: 140 evaluable, 47% received maintenance

    • utDNA-: no significant RFS benefit from maintenance (HR 1.35, 0.50-3.64, P=0.6); 24-month RFS 88% with or without maintenance.
    • utDNA+: maintenance associated with better RFS (HR 0.22, 0.09-0.52, P<0.001); 24-month RFS 68% with maintenance vs 16% without.
    • Observational; not a randomized test of utDNA-guided maintenance.

  24. Bibliographic catalog

    Additional verified 2025-2026 utDNA citations

Genitourinary

Level 1

Conference data

  • Level 1positiveASCO Annual Meeting 2026

    Patient-reported outcomes from IMvigor011: A phase 3 study of circulating tumor (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer (MIBC).

    Bellmunt, Joaquim · Abstract 4627 · IMvigor011 · 250 ctDNA-positive patients randomized (167 atezolizumab, 83 placebo)

    not named in the abstract

    Time to confirmed deterioration in physical functioning, role functioning, and global health status/quality of life showed no evidence of a difference between atezolizumab and placebo. More than 90% of patients in both arms reported little or no treatment side-effect burden through cycle 11. The abstract concludes ctDNA-guided adjuvant atezolizumab improved DFS and OS without negatively affecting patient-reported quality of life.

    Full paper

  • Level 1mixedASCO Genitourinary Cancers Symposium 2026

    Circulating tumor DNA (ctDNA) to guide response-adapted bladder preservation in muscle invasive bladder cancer (MIBC).

    Ghatalia, Pooja · Abstract LBA632 · LBA · RETAIN-2 (and combined RETAIN-1/2) · 71 evaluable RETAIN-2 patients; combined ctDNA analysis across RETAIN-1/2: 274 timepoints from 111 patients

    Signatera (named in the abstract)

    Estimated 2-year metastasis-free survival was 79.8% in the RETAIN-2 ITT population; the abstract states RETAIN-2 is expected to meet its primary MFS endpoint. Among 22 active-surveillance patients, 16 (73%) remained metastasis-free with an intact bladder. Post-treatment ctDNA negativity or clearance predicted lower recurrence (34.8% and 43.8%) than persistent positivity or non-clearance (85.7% and 91.7%). Among active-surveillance patients who were ctDNA-negative after treatment, 24-month MFS was 82.4% but 24-month RFS was 50.7%, driven by local recurrences: 19 of 22 who recurred on active surveillance were ctDNA-negative after treatment.

  • Level 1positiveASCO Genitourinary Cancers Symposium 2026

    Circulating tumor (ct)DNA-guided adjuvant atezolizumab (atezo) in muscle-invasive bladder cancer (MIBC): Exploratory analysis of ctDNA dynamics in the IMvigor011 trial.

    Powles, Thomas · Abstract 633 · IMvigor011 · 379 patients who tested ctDNA-positive during surveillance; on-treatment dynamics in 165 atezolizumab and 83 placebo

    not named in the abstract (results reported as mean tumor molecules/mL)

    Of patients first testing ctDNA-positive, 74.1% (281/379) did so within 24 weeks of radical cystectomy; early positivity and higher baseline concentration (median 0.27 MTM/mL) were associated with shorter investigator-assessed DFS. Atezolizumab decreased ctDNA levels between cycle 1 and 3 (log2 fold-change -0.4) while levels increased on placebo (log2 fold-change 0.5; Wilcoxon P=0.009). Clearance at cycle 3 or 5 was associated with improved DFS and OS.

    Full paper

  • Level 1positiveESMO Congress 2025

    LBA8 IMvigor011: A phase III trial of circulating tumour (ct)DNA-guided adjuvant atezolizumab vs placebo in muscle-invasive bladder cancer

    Powles, T.B. · Abstract LBA8 · LBA · IMvigor011 · 761 enrolled in surveillance; 250 ctDNA-positive patients randomized (167 atezolizumab, 83 placebo); 357 persistently ctDNA-negative

    not named in the abstract

    Among 250 eligible ctDNA-positive patients after cystectomy, adjuvant atezolizumab improved investigator-assessed DFS versus placebo (median 9.9 vs 4.8 months; HR 0.64, 95% CI 0.47-0.87; P=0.0047) and OS (median 32.8 vs 21.1 months; HR 0.59, 95% CI 0.39-0.90; P=0.0131). In 357 patients who remained ctDNA-negative, DFS was 95.4% at the end of 1-year monitoring and 88.4% at 2 years.

    Full paperSlidesWebcastSlides + webcast. An ASCO or ESMO member login may be required.

Level 2

Conference data

Level 3

Conference data

GI, including colorectal

Level 1

Conference data

Level 2

Conference data

Level 3

Conference data

Breast

Level 1

Conference data

Level 2

Conference data

  • Level 2ESMO Breast Cancer 2026

    416O - SMART: On-treatment ctDNA dynamics predicts response and progression in metastatic breast cancer

    Pedram Razavi · Abstract 416O · Proffered Paper (oral) · SMART

    SlidesWebcastSlides + webcast. An ASCO or ESMO member login may be required.

  • Level 2prognosticASCO Annual Meeting 2025

    Circulating tumor DNA and late recurrence in high-risk, hormone receptor-positive, HER2-negative breast cancer: An updated analysis of the CHiRP study.

    Yoo, Tae-Kyung Robyn · Abstract 3055 · CHiRP · same 83-patient analytic cohort as the 2022 abstract; median follow-up from first sample 4.4 years; 214 plasma samples before known recurrence

    RaDaR (tumor-informed, whole-exome-based)

    With longer follow-up, all 8/8 patients with ctDNA detected at any timepoint developed distant recurrence (median lead time 1.39 years, range 0.01-4.24). A negative test had a negative predictive value for remaining recurrence-free of 100% at more than 1 year (0/196), 98.4% at more than 2 years (3 events among 185 samples), and 96.6% at more than 3 years (5/147).

  • Level 2prognosticSan Antonio Breast Cancer Symposium 2025

    Abstract RF3-05: Tissue-free circulating tumour DNA detection in patients with early triple negative breast cancer from the c-TRAK-TN trial

    Cunningham, N. · Abstract RF3-05 · c-TRAK TN · 1,062 timepoints from 159 patients; 1,012 (95.3%) successfully analyzed with the tissue-free assay; 1,005 timepoints compared with ddPCR

    Guardant Reveal (tissue-free methylation) compared with digital droplet PCR (1-2 patient-specific variants)

    ctDNA was detected by Reveal in 54/159 (34.0%) patients at least once and was associated with relapse (HR 20.62, P<0.0001). Of patients who relapsed by 24 months, 34/38 (89.5%) had prior ctDNA detection. Agreement with ddPCR was 94.5% (950/1005 timepoints). Among detections, 44.8% were first found by the tissue-free assay and 6.9% by ddPCR. Median time from first detection to relapse was 7.9 months with Reveal vs 5.7 months with ddPCR (HR 0.6, P=0.0574).

    Full paper

  • Level 2prognosticASCO Annual Meeting 2024

    Ultra-sensitive ctDNA mutation tracking to identify molecular residual disease and predict relapse in patients with early breast cancer.

    Garcia-Murillas, Isaac · Abstract 1010 · ChemoNEAR · 76 patients with early breast cancer (23 TNBC, 33 HER2-positive, 16 HR-positive, 4 unknown); 598 plasma samples

    NeXT Personal (Personalis), tumor-informed whole-genome personalized panels of up to about 1,800 variants

    At a median follow-up of 76 months, ctDNA detection was associated with relapse (HR undefined, P<0.0001) and shorter OS (P<0.0001), with a median lead time of 12.5 months (range 1-60). MRD was identified in 10/10 patients who relapsed (median 18.5 PPM at first detection). None of 58 patients who remained ctDNA-undetected relapsed. Of patients undetected at the post-surgical landmark, 31/33 (94%) did not relapse. Forty percent of all detections were below 100 PPM.

  • Level 2prognosticASCO Annual Meeting 2022

    Circulating tumor DNA (ctDNA) and late recurrence in high-risk, hormone receptor–positive, HER2-negative breast cancer (CHiRP).

    Lipsyc-Sharf, Marla · Abstract 103 · CHiRP · 103 enrolled; 83 with successful whole-exome sequencing and personalized assays; 219 plasma samples

    RaDaR (personalized, tumor-informed; 12-51 variants, median 36)

    At a median of 8.4 years from diagnosis to first sample, 8/83 (10%) were MRD-positive at any timepoint and 4/83 (5%) were positive at study entry. All 5 patients with distant metastatic recurrence were MRD-positive, with ctDNA lead times up to 37.6 months. Two of 8 MRD-positive patients had not recurred at latest follow-up.

  • Level 2prognosticSan Antonio Breast Cancer Symposium 2022

    Abstract PD5-03: PD5-03 Comparison of a personalized sequencing assay and digital PCR for circulating tumor DNA based Molecular Residual Disease detection in early-stage triple negative breast cancer in the cTRAK-TN trial

    Coakley, Maria · Abstract PD5-03 · poster discussion · c-TRAK TN · Agreement and lead-time comparison on c-TRAK TN samples; exact patient n is given in rates (9 patients RaDaR-only positive, 3 dPCR-only) but a single total n is not restated as a standalone figure in the extracted results beyond the agreement analysis

    RaDaR (personalized multi-mutation sequencing) compared with digital PCR mutation tracking

    Overall test agreement was 92.7% (95% CI 90.7-94.4%). From a patient-level view, 58.7% were negative on both assays, 32.9% positive on both, and 8.6% discordant (ctDNA detected by RaDaR but not dPCR in 9 patients, and the reverse in 3). Among ctDNA-positive patients, 55.2% were first detected by RaDaR, 5.2% by dPCR, and 39.6% at the same timepoint (P<0.001). Median lead time to relapse was 7.1 months with RaDaR vs 5.7 months with dPCR.

    Full paper

Level 3

Trial in progress

Registered study, no results paper yet

NCT06230185 B-STRONGER-I: ctDNA MRD testing during neoadjuvant chemotherapy for stage I–III triple-negative breast cancer. Sponsor: Personalis Inc.. ClinicalTrials.gov lists the study as recruiting. Prospective observational cohort. The registry primary outcome is the correlation of molecular residual disease, measured with the NeXT Personal clinical-trial assay, with pathologic complete response after neoadjuvant chemotherapy. No peer-reviewed results paper or public poster was found.

Lung

Level 2

Conference data

Level 3

Conference data

  • Level 3ESMO Congress 2026

    Clinical utility of ultra-sensitive ctDNA MRD monitoring in advanced NSCLC

    Srushti Borkar · Abstract 2728eP · ePoster

    PosterPoster PDF. An ASCO or ESMO member login may be required.

  • Level 3prognosticASCO Annual Meeting 2021

    Leveraging phased variants for personalized minimal residual disease detection in localized non-small cell lung cancer.

    Kurtz, David Matthew · Abstract 8518 · Personalized PhasED-Seq applied in 5 patients with localized NSCLC (14 plasma samples); methodologic series

    PhasED-Seq (personalized phased-variant sequencing after tumor/normal whole-genome sequencing)

    Phased variants had a lower background rate than SNVs, including duplex SNVs (1.2e-6 vs 3.8e-5 and 1.0e-5). PhasED-Seq detected all 5 SNV-positive samples and 5 additional samples at tumor fractions as low as 0.000094%. In one patient with stage III adenocarcinoma, PhasED-Seq detected MRD in three on-treatment samples that were undetectable by SNVs, including a sample 8 months before progression.

Trial in progress

Head and neck

Level 1

Level 2

Level 3

Conference data

Melanoma

Level 2

Conference data

  • Level 2prognosticASCO Annual Meeting 2025

    Longitudinal ctDNA monitoring for post-surgical molecular residual disease in patients with stage I-IIIb melanoma.

    Ansstas, George · Abstract 9571 · 197 patients; 1,718 plasma samples; retrospective real-world series; median 7 tests per patient over a median 24.7 months

    Signatera (personalized tumor-informed 16-plex mPCR-NGS)

    ctDNA positivity at any postoperative timepoint was associated with shorter RFS (HR 15.0, 95% CI 7.3-31.0, P<0.0001), particularly for distant or regional recurrence (HR 27.0). In a multivariate analysis (n=163), ctDNA positivity remained associated with RFS (HR 10.50, 95% CI 3.891-28.32, P<0.001). The abstract states ctDNA positivity influenced treatment-management changes in 28/38 (73.7%) of patients in whom that question was assessed.

  • Level 2prognosticASCO Annual Meeting 2023

    Minimal residual disease by circulating tumor DNA as a biomarker of recurrence free survival in resected high-risk melanoma patients treated with mRNA-4157/V940, a personalized cancer vaccine, and pembrolizumab.

    Carlino, Matteo S. · Abstract LBA9515 · LBA · KEYNOTE-942 (mRNA-4157-P201) · 125 patients with evaluable baseline ctDNA; 110 (88%) ctDNA-negative at start of treatment

    RaDaR (as stated in prior reports of this analysis; confirm brand is named in this abstract body if cited as such)

    Baseline ctDNA-negativity was associated with longer RFS than positivity (event rate 20.9% [23/110] vs 80.0% [12/15]; HR 0.150, 95% CI 0.073-0.306). In the mRNA-4157/V940 plus pembrolizumab arm, RFS event rates were 10.4% (8/77) if negative vs 76.9% (10/13) if positive (HR 0.087). The pembrolizumab monotherapy comparison used only 2 ctDNA-positive patients.

Level 3

Conference data

  • Level 3prognosticASCO Annual Meeting 2023

    Longitudinal circulating tumor DNA monitoring for detection of molecular residual disease in patients with surgically resected stage II/III melanoma.

    Kollipara, Revathi · Abstract 9582 · 45 patients; assays designed for 42/45 (93%); 159 plasma samples; single-center real-world series

    Signatera (bespoke mPCR-NGS)

    ctDNA was detectable at one or more timepoints in 15/42 (36%), including 11/20 (55%) with stage III and 4/22 (18%) with stage II disease. Radiographic recurrence occurred in 7/42 patients, 6 of whom were ctDNA-positive. 26/27 (96%) patients with persistent ctDNA negativity remained clinically and radiographically progression-free. Twelve of 15 ctDNA-positive patients received adjuvant immunotherapy or treatment escalation after a positive result; 6 had sustained clearance.

Gynecologic

Level 2

Conference data

Level 3

Heme

Level 1

Level 2

Conference data

  • Level 2prognosticASH Annual Meeting 2022

    Risk Profiling of Patients with Previously Untreated Diffuse Large B-Cell Lymphoma (DLBCL) By Measuring Circulating Tumor DNA (ctDNA): Results from the POLARIX Study

    Herrera, Alex F. · Abstract 1297 · POLARIX · paired baseline and Cycle 2 Day 1 results in 319/440 (Pola-R-CHP) and 299/439 (R-CHOP) patients

    AVENIO NHL CAPP-Seq; results as mean mutant molecules per mL

    Baseline ctDNA above the median MMPM was associated with shorter PFS and OS in both arms (Pola-R-CHP PFS HR 1.96, OS HR 2.17; R-CHOP PFS HR 1.43, OS HR 2.10). A log-fold change of at least 2.0 or undetectable ctDNA at C2D1 was reached by 66.8% and 65.6% of patients in the two arms and was prognostic (PFS HR 1.86 and 2.21). In Pola-R-CHP, a 2.5-log reduction (PFS HR 2.89) and C2D1 clearance (PFS HR 2.98, OS HR 2.74) remained prognostic independent of baseline risk factors.

Level 3

Conference data

  • Level 3prognosticASCO Annual Meeting 2021

    Personalized, ctDNA analysis to detect minimal residual disease and identify patients at high risk of relapse with multiple myeloma.

    Dhakal, Binod · Abstract 8029 · 28 patients after upfront autologous transplant; 80 plasma timepoints; median follow-up 92.4 months; single-center retrospective

    Signatera (personalized tumor-informed mPCR-NGS), assessed about 3 months after transplant; bone-marrow comparison used multiparameter flow cytometry at 10^-4

    ctDNA was detectable in 17/24 (70.8%) before transplant, 15/28 (53.6%) at about 3 months after transplant, and 11/28 (39.2%) during later surveillance. Of 15 patients MRD-positive at 3 months, 14 (93.3%) later relapsed (HR 5.64, 95% CI 1.8-17, P=0.0003). Median PFS was 84 months if ctDNA-negative at 3 months vs 31 months if positive (P=0.003). The 3-month positive predictive value for relapse was 93.3%, higher than marrow flow cytometry (68.4%) in this series.

Hematologic MRD records

Myeloma

  • Level 1myelomapositive2024 · 2024-04-12

    FDA Oncologic Drugs Advisory Committee vote on MRD as an accelerated-approval endpoint in multiple myeloma

    Oncologic Drugs Advisory Committee, U.S. Food and Drug Administration. FDA ODAC meeting minutes.

    ODAC voted Yes 12, No 0, Abstain 0 on: 'Does the evidence support the use of MRD as an accelerated approval endpoint in MM clinical trials?' Committee discussion supported use in both newly diagnosed and relapsed/refractory settings, with 9-month, 12-month, and MRD-negative CR at any time considered acceptable assessment timepoints. Minutes approved July 2, 2024.

    IMF account of the vote

  • Level 1myelomapositive2026 · 2026-01-20

    Minimal Residual Disease and Complete Response in Multiple Myeloma: Use as Endpoints to Support Accelerated Approval (Draft Guidance for Industry)

    U.S. Food and Drug Administration (OCE, CDER, CBER, CDRH). FDA draft guidance; Docket FDA-2025-D-2616. Bone-marrow flow cytometry or sequencing; threshold of at least 1 in 10^5

    Draft guidance, posted on the FDA site on January 20, 2026 (Federal Register notice January 21, 2026). Recommends MRD-negativity rate (in patients who have achieved CR or stringent CR), assessed in bone marrow by flow or sequencing, and CR rate as primary endpoints to support accelerated approval. MRD negativity should be assessed at a threshold of at least 1 in 10^5 residual tumor cells; alternate thresholds require justification. Verification of clinical benefit (typically PFS or OS) will generally be required, and confirmatory trial(s) should generally be underway prior to accelerated approval. Comments were due March 23, 2026.

    PDFFederal Register notice

  • Level 1myelomapositive2026 · 2026-08-13

    FDA accelerated approval of iberdomide (Zenbexus) with daratumumab and hyaluronidase-fihj and dexamethasone

    U.S. Food and Drug Administration. FDA Cancer Approvals. MRD-negative complete response at any time (EXCALIBER-RRMM) · n=420

    Accelerated approval on August 13, 2026, for adults with multiple myeloma after at least one prior line including a proteasome inhibitor and an immunomodulatory agent, in combination with daratumumab and hyaluronidase-fihj and dexamethasone. In the first 420 randomized patients (IberDd n=207 vs DVd n=213), MRD-negative CR at any time was 41% (95% CI 34-48) vs 21% (95% CI 15-27), p<0.0001. Continued approval may depend on confirmatory verification of clinical benefit. The trial remains ongoing for PFS.

    Prescribing information

  • Level 1myeloma/ALLpositive2018 · 2018-09-28

    FDA authorizes clonoSEQ, the first NGS-based MRD test for multiple myeloma and B-cell ALL

    U.S. Food and Drug Administration. FDA press announcement (De Novo DEN170080). clonoSEQ NGS, bone marrow

    On September 28, 2018, FDA granted De Novo authorization for Adaptive Biotechnologies' clonoSEQ assay to detect and monitor MRD in bone-marrow samples from patients with multiple myeloma or B-cell acute lymphoblastic leukemia, with the agency describing detection of remaining cancer cells at very low levels (down to about 1 in 1,000,000 cells).

    De Novo decision summary

  • Consensusmyelomapositive2016

    International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma

    Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, et al.. Lancet Oncol. PMID 27511158. Flow cytometry or sequencing MRD, with or without imaging

    IMWG defined MRD-negativity response categories (with or without imaging-based absence of extramedullary disease) to allow uniform reporting, using bone-marrow flow or sequencing plus sensitive imaging, on top of conventional CR.

  • Level 2myelomapositive2017

    Association of Minimal Residual Disease With Superior Survival Outcomes in Patients With Multiple Myeloma: A Meta-analysis

    Munshi NC, Avet-Loiseau H, Rawstron AC, Owen RG, Child JA, Thakurta A, et al.. JAMA Oncol. PMID 27632282. Heterogeneous MRD methods across included studies · n=1,273 (PFS, 14 studies); 1,100 (OS, 12 studies)

    Among 21 eligible studies, MRD negativity was associated with better PFS (HR 0.41, 95% CI 0.36-0.48, P<.001) and OS (HR 0.57, 95% CI 0.46-0.71, P<.001). In patients already in conventional CR, PFS HR was 0.44 (0.34-0.56) and OS HR 0.47 (0.33-0.67).

    Full text

  • Level 3myelomapositive2017

    Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma

    Flores-Montero J, Sanoja-Flores L, Paiva B, Puig N, García-Sánchez O, Böttcher S, et al.. Leukemia. PMID 28104919. EuroFlow NGF, bone marrow · n=110

    EuroFlow 2-tube 8-color NGF with acquisition of ≥10^7 cells; LOD <2×10^-6 and LOQ <5×10^-6. In 110 BM samples from patients in VGPR or CR, MRD-positive rate was 47% by NGF vs 34% by conventional 8-color flow (P=0.003); 25% of conventional MRD-negative cases were NGF-positive. NGF MRD-negative vs MRD-positive CR patients had longer PFS (75% PFS not reached vs 7 months; P=0.02).

    Full text

  • Level 2myelomapositive2020

    A large meta-analysis establishes the role of MRD negativity in long-term survival outcomes in patients with multiple myeloma

    Munshi NC, Avet-Loiseau H, Anderson KC, Neri P, Paiva B, Samur M, et al.. Blood Adv. PMID 33284948. Heterogeneous (flow and sequencing) across 44 studies · n=8,098 (PFS, 44 studies); 4,297 (OS, 23 studies)

    MRD negativity vs positivity improved PFS (HR 0.33, 95% CI 0.29-0.37, P<.001) and OS (HR 0.45, 95% CI 0.39-0.51, P<.001), including across newly diagnosed and relapsed/refractory disease, MRD thresholds, cytogenetic risk, and method of assessment.

    Full text

  • Level 2myelomapositive2020

    Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial

    Voorhees PM, Kaufman JL, Laubach J, Sborov DW, Reeves B, Rodriguez C, et al.. Blood. PMID 32325490. MRD (NGS, 10^-5) as a key secondary endpoint · n=207

    Randomized phase 2 trial of D-RVd vs RVd in 207 transplant-eligible NDMM patients. Primary endpoint, sCR by the end of post-ASCT consolidation, was 42.4% vs 32.0% (OR 1.57, 95% CI 0.87-2.82; 1-sided P=0.068), meeting the prespecified 1-sided alpha of 0.10. With median follow-up 22.1 months, sCR improved to 62.6% vs 45.4% (P=0.0177) and MRD negativity (10^-5, ITT) was 51.0% vs 20.4% (P<.0001). 24-month PFS 95.8% vs 89.8%. MRD analysis of a randomized phase 2 trial (level 2), not MRD-guided therapy.

    Full text

  • Level 2myelomamixed2022

    Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma: The MASTER Trial (primary analysis)

    Costa LJ, Chhabra S, Medvedova E, Dholaria BR, Schmidt TM, Godby KN, et al.. J Clin Oncol. PMID 34898239. NGS MRD (clonoSEQ lineage), 10^-5 primary; 10^-6 also reported · n=123

    Single-arm phase 2 MRD-adapted Dara-KRd with AHCT (n=123). Primary endpoint MRD <10^-5: 80% overall (78%, 82%, and 79% for 0, 1, and 2+ HRCAs); 66% reached MRD <10^-6; 71% had two consecutive MRD-negative assessments and entered treatment-free surveillance. Two-year PFS was 87% (91%, 97%, and 58% for 0, 1, and 2+ HRCAs). 12-month incidence of MRD resurgence or progression after cessation was 4%, 0%, and 27% by HRCA group. Not a randomized trial, so filed as level 2 despite being MRD-guided.

  • Level 2myelomamixed2023

    Minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma (MASTER): final report of the multicentre, single-arm, phase 2 trial

    Costa LJ, Chhabra S, Medvedova E, Dholaria BR, Schmidt TM, Godby KN, et al.. Lancet Haematol. PMID 37776872. NGS MRD, 10^-5 (MRD-evaluable n=118 of 123) · n=123

    Final analysis, median follow-up 42.2 months. Of 118 MRD-evaluable patients, 96 (81%, 95% CI 73-88) reached MRD <10^-5 and 84 (71%, 62-79) reached MRD-SURE and stopped therapy. 36-month PFS: 88% (no HRCA), 79% (1 HRCA), 50% (2+ HRCAs). Among 84 who stopped therapy, 24-month cumulative incidence of progression from cessation was 9%, 9%, and 47% by HRCA group. MRD-adapted cessation was feasible in 0-1 HRCA disease; patients with 2+ HRCAs had higher progression after stopping.

    Full text

  • Level 2myelomapositive2022

    Addition of isatuximab to lenalidomide, bortezomib, and dexamethasone as induction therapy for newly diagnosed, transplantation-eligible patients with multiple myeloma (GMMG-HD7): a randomised, open-label, multicentre, phase 3 trial

    Goldschmidt H, Mai EK, Bertsch U, Fenk R, Nievergall E, Tichy D, et al.. Lancet Haematol. PMID 36328040. Flow-cytometry MRD after induction (primary endpoint of part 1) · n=660

    Phase 3, 660 transplant-eligible NDMM patients (331 Isa-VRd, 329 VRd) in Germany. MRD negativity after induction (ITT) was reached in 166 (50%) vs 117 (36%) (OR 1.82, 95% CI 1.33-2.48; p=0.00017). Grade 3-4 neutropenia 23% vs 7%. MRD analysis of an RCT (level 2), not MRD-guided therapy. NCT03617731.

  • Level 2myelomapositive2025

    Isatuximab, Lenalidomide, Bortezomib, and Dexamethasone Induction Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma: Final Part 1 Analysis of the GMMG-HD7 Trial

    Mai EK, Bertsch U, Pozek E, Fenk R, Besemer B, Hanoun C, et al.. J Clin Oncol. PMID 39652594. MRD after Isa-VRd vs VRd induction · n=662

    Final part 1 analysis of GMMG-HD7 (331 Isa-RVd, 329 RVd). MRD-negativity rates continued to deepen after transplant (66% Isa-RVd vs 48% RVd). Isa-RVd induction significantly prolonged PFS vs RVd regardless of maintenance (HR 0.70, 95% CI 0.52-0.95, P=0.0184). Level 2 (MRD and PFS analysis of a randomized trial).

    Full text

  • Level 2myelomapositive2024

    Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma (PERSEUS)

    Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, et al.. N Engl J Med. PMID 38084760. MRD negativity as a key secondary endpoint (threshold as prespecified in the protocol; reported as MRD-negative status) · n=709

    Phase 3 trial, 709 transplant-eligible NDMM patients randomized to D-VRd (with D-R maintenance) vs VRd (with R maintenance). At median follow-up 47.5 months, 48-month PFS was 84.3% vs 67.7% (HR 0.42, 95% CI 0.30-0.59, P<0.001). CR or better 87.9% vs 70.1% (P<0.001); MRD-negative status 75.2% vs 47.5% (P<0.001). MRD analysis of an RCT (level 2), not MRD-guided therapy.

  • Level 2myelomapositive2024

    EVIDENCE meta-analysis: evaluating minimal residual disease as an intermediate clinical end point for multiple myeloma

    Landgren O, Prior TJ, Masterson T, Heuck C, Bueno OF, Dash AB, et al.. Blood. PMID 38768337. MRD negativity at 12±3 months (trial-level and individual-level association with PFS) · n=4907

    FDA-aligned meta-analysis of 8 newly diagnosed MM randomized trials (n=4,907). Trial-level association between 12-month MRD negativity and PFS: R²_WLSiv 0.67 (95% CI 0.43-0.91) and R²_copula 0.84 (0.64 to >0.99). Individual-level global OR for 12-month MRD negativity and PFS was 4.02 (95% CI 2.57-5.46) in NDMM and 7.67 (4.24-11.10) in 4 relapsed/refractory studies. Supported the case that a treatment effect on MRD is reasonably likely to predict a treatment effect on PFS. One of the two meta-analyses presented at the April 2024 ODAC.

    Full text

  • Level 2myelomapositive2025

    Minimal Residual Disease-Based End Point for Accelerated Assessment of Clinical Trials in Multiple Myeloma: A Pooled Analysis of Individual Patient Data From Multiple Randomized Trials (i2TEAMM)

    Shi Q, Paiva B, Pederson LD, Dimier N, Talpes E, Prior TJ, et al.. J Clin Oncol. PMID 39938021. MRD-negative CR at 10^-5, at 9 or 12 months · n=4773

    Individual-patient meta-analysis from 20 randomized trials; 11 studies (4,773 patients) evaluated 9- or 12-month MRD-CR at a 10^-5 threshold as an intermediate endpoint for PFS/OS in ND transplant-eligible, ND transplant-ineligible, and RRMM. Patient-level global ORs for MRD-CR and PFS ranged from 3.06 to 16.24 (all 95% CIs excluded 1.0). Trial-level R² 0.61-0.70 overall and 0.67-0.78 in newly diagnosed disease. Supported use of 9- or 12-month MRD-CR at 10^-5 as an intermediate endpoint for accelerated approval. This is the i2TEAMM pooled analysis presented at ODAC.

  • Level 2myelomapositive2025

    Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial

    Perrot A, Touzeau C, Lambert J, Hulin C, Caillot D, Karlin L, et al.. Blood. PMID 39841461. NGS MRD at 10^-5 and 10^-6 after Isa-KRd induction · n=791

    Induction analysis of the MRD-adapted MIDAS trial: 791 patients received six 28-day cycles of Isa-KRd. 96% completed induction; best ORR 95%; 91% achieved VGPR or better. In the ITT population, MRD-negativity rates after induction were 63% at 10^-5 and 47% at 10^-6.

    Full text

  • Level 1myelomamixed2025

    Measurable Residual Disease-Guided Therapy in Newly Diagnosed Myeloma (MIDAS)

    Perrot A, Lambert J, Hulin C, Pieragostini A, Karlin L, Arnulf B, et al.. N Engl J Med. PMID 40459097. NGS MRD, 10^-5 to assign consolidation; primary endpoint 10^-6 MRD negativity before maintenance · n=485 MRD-negative at 10^-5 after induction; 233 MRD-positive at 10^-5

    Phase 3 randomized MRD-guided consolidation after Isa-KRd induction. Among 485 patients MRD-negative at 10^-5 after induction, premaintenance MRD negativity at 10^-6 was 86% with ASCT + 2 cycles Isa-KRd vs 84% with 6 cycles Isa-KRd without ASCT (adjusted RR 1.02, 95% CI 0.95-1.10, P=0.64). Among 233 patients MRD-positive at 10^-5, premaintenance 10^-6 negativity was 32% with tandem ASCT vs 40% with single ASCT + Isa-KRd (adjusted RR 0.82, 95% CI 0.58-1.15, P=0.31). Median follow-up about 16-17 months. Neither intensification strategy significantly improved the 10^-6 MRD endpoint. Level 1 (randomized MRD-guided trial).

    Full text

  • Level 3myelomamixed2024

    Discontinuation of maintenance therapy in multiple myeloma guided by multimodal measurable residual disease negativity (MRD2STOP)

    Derman BA, Major A, Cooperrider J, Jiang K, Ramsland A, Karrison T, Kubicki T, Jakubowiak AJ. Blood Cancer J. PMID 39375362. Multimodal: PET, BM flow (LoD 10^-5), BM clonoSEQ (LoD 10^-6), plus CD138-enriched clonoSEQ toward 10^-7 · n=47

    Pragmatic trial: 47 patients with prior MRD <10^-5, ≥1 year of maintenance, and prospectively confirmed undetectable disease by PET, BM flow (10^-5), and BM clonoSEQ (10^-6) discontinued maintenance (median prior maintenance 36 months). Median post-discontinuation follow-up 30 months. Baseline MRD ≥10^-7 in 9/47 (19%). Estimated 3-year cumulative incidence of disease resurgence was 20% if baseline MRD <10^-7 vs 75% if ≥10^-7 (HR 7.8, 95% CI 2.2-27.6, P=0.001); 3-year PFS 92% vs 49% (HR 10.1, 95% CI 1.6-62.3). Small single-arm study (level 3).

    Full textASCO abstract 106ClinicalTrials.gov NCT04108624

  • Level 2myelomapositive2025

    Daratumumab-bortezomib-thalidomide-dexamethasone for newly diagnosed myeloma: CASSIOPEIA minimal residual disease results

    Corre J, Vincent L, Moreau P, Hebraud B, Hulin C, Béné MC, et al.. Blood. PMID 40127397. MRD at 10^-5 and 10^-6 at prespecified time points

    Long-term MRD and PFS after median follow-up 80.1 months. D-VTd improved MRD-negativity (10^-5) after induction (34.6% vs 23.1%) and consolidation (63.7% vs 43.7%) vs VTd. Daratumumab maintenance (fixed duration ≤2 years vs observation; not MRD-guided) further improved MRD-negativity (D-VTd/dara vs D-VTd/observation: 10^-5 77.3% vs 70.7%, 10^-6 60.7% vs 52.0%; VTd/dara vs VTd/observation: 10^-5 70.9% vs 51.2%, 10^-6 48.4% vs 30.7%) and provided PFS benefit regardless of post-consolidation MRD status. Correction: this is not an MRD-guided maintenance trial.

    Full text

  • Level 2myelomapositive2025

    Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial

    Usmani SZ, Facon T, Hungria V, Bahlis NJ, et al.. Nat Med. PMID 39910273. MRD negativity (and sustained MRD negativity) as a key endpoint · n=395

    Phase 3 D-VRd vs VRd in transplant-ineligible or transplant-deferred NDMM. At median follow-up 58.7 months, MRD-negativity rate 60.9% vs 39.4% (OR 2.37, 95% CI 1.58-3.55, P<0.0001); ≥CR 81.2% vs 61.6% (P<0.0001); sustained MRD negativity ≥12 months 48.7% vs 26.3% (P<0.0001). Risk of progression or death was 43% lower with D-VRd (HR 0.57, 95% CI 0.41-0.79, P=0.0005). Level 2. A dedicated MRD analysis is Zweegman et al., Blood Adv 2026 (PMID 42234958).

    Full text

  • Level 3myelomapositive2024

    Monitoring Minimal Residual Disease in Patients with Multiple Myeloma by Targeted Tracking Serum M-Protein Using Mass Spectrometry (EasyM)

    Fan H, Wang B, Shi L, Pan N, et al.. Clin Cancer Res. PMID 38170583. EasyM clonotypic serum mass spectrometry

    Method and clinical-monitoring paper for EasyM, a peripheral-blood clonotypic mass-spectrometry assay tracking serum M-protein for MRD in myeloma.

    Full text

  • Level 3myelomapositive2025

    Comparison of EasyM, a clonotypic mass spectrometry assay, and EuroFlow minimal residual disease assessment in multiple myeloma

    Zhao J, Khong T, Gorniak M, Khaled A, et al.. Haematologica. PMID 39506908. EasyM (serum MS) vs EuroFlow NGF (bone marrow)

    Head-to-head comparison of the blood-based EasyM clonotypic mass-spectrometry assay with EuroFlow bone-marrow MRD in myeloma (Haematologica 2025). The PubMed record did not include a structured abstract with numeric concordance rates at retrieval, so rates are not restated here; the paper and DOI were verified.

    Full text

  • Level 1myelomapending2019

    SWOG S1803 DRAMMATIC: daratumumab-lenalidomide vs lenalidomide maintenance with MRD-adapted duration in newly diagnosed myeloma after transplant

    SWOG / NCI NCTN. ClinicalTrials.gov. MRD-adapted maintenance duration

    Ongoing randomized MRD-adapted maintenance trial. No primary efficacy results paper was identified as of this review. Included as a level-1-design trial (MRD-integral randomization) without outcome data.

  • Level 2myelomapositive2026

    Daratumumab in transplant-ineligible or -deferred newly diagnosed multiple myeloma: minimal residual disease in CEPHEUS

    Zweegman S, Facon T, Hungria V, Bahlis NJ, et al.. Blood Adv. PMID 42234958. MRD at 10^-5 and 10^-6, including sustained MRD negativity · n=395

    395 patients (D-VRd 197, VRd 198), median follow-up 58.7 months. Overall MRD-negativity 10^-5: 60.9% vs 39.4% (OR 2.37, 95% CI 1.58-3.55, P<.0001); 10^-6: 46.2% vs 27.3% (OR 2.24, 95% CI 1.48-3.40, P=0.0001). Sustained MRD negativity ≥12 months 10^-5: 49.2% vs 27.3%; 10^-6: 34.0% vs 16.2% (each P<.0001), with similar benefits at ≥24 and ≥36 months. Among patients who achieved MRD negativity, PFS trended in favor of D-VRd (10^-5 HR 0.61, 95% CI 0.35-1.06, P=0.0755).

    Full text

ALL

  • Level 1myeloma/ALLpositive2018 · 2018-09-28

    FDA authorizes clonoSEQ, the first NGS-based MRD test for multiple myeloma and B-cell ALL

    U.S. Food and Drug Administration. FDA press announcement (De Novo DEN170080). clonoSEQ NGS, bone marrow

    On September 28, 2018, FDA granted De Novo authorization for Adaptive Biotechnologies' clonoSEQ assay to detect and monitor MRD in bone-marrow samples from patients with multiple myeloma or B-cell acute lymphoblastic leukemia, with the agency describing detection of remaining cancer cells at very low levels (down to about 1 in 1,000,000 cells).

    De Novo decision summary

  • Level 1ALLpositive2018 · 2018-03-29

    FDA expands blinatumomab (Blincyto) approval to MRD-positive B-cell precursor ALL

    U.S. Food and Drug Administration. FDA press announcement. MRD ≥10^-3 (0.1%) as the eligibility threshold in BLAST

    On March 29, 2018, FDA granted accelerated approval of blinatumomab for adults and children with B-cell precursor ALL in first or second complete remission with MRD ≥0.1%, based on the single-arm BLAST study. Supporting trial results are in Gökbuget et al., Blood 2018 (PMID 29358182).

  • Level 2ALLpositive2018

    Blinatumomab for minimal residual disease in adults with B-cell precursor acute lymphoblastic leukemia (BLAST)

    Gökbuget N, Dombret H, Bonifacio M, Reichle A, Graux C, Faul C, et al.. Blood. PMID 29358182. MRD ≥10^-3 at eligibility; complete MRD response after cycle 1 (primary endpoint) · n=116

    Open-label single-arm study: 116 adults with B-cell precursor ALL in hematologic CR with MRD ≥10^-3 received blinatumomab for up to 4 cycles. 88 of 113 evaluable patients (78%) achieved a complete MRD response after 1 cycle. In 110 Ph-negative patients, 18-month RFS was 54%; median OS 36.5 months. Complete MRD responders had longer RFS (23.6 vs 5.7 months, P=0.002) and OS (38.9 vs 12.5 months, P=0.002) than nonresponders. This trial supported the March 29, 2018 FDA approval. Single-arm (level 2); the approval itself is filed as regulatory level 1.

    Full text

  • Level 2ALLpositive2020

    Dasatinib-Blinatumomab for Ph-Positive Acute Lymphoblastic Leukemia in Adults (D-ALBA / GIMEMA LAL2116)

    Foà R, Bassan R, Vitale A, Elia L, Piciocchi A, Puzzolo MC, et al.. N Engl J Med. PMID 33085860. Molecular MRD in Ph+ ALL

    Chemo-free induction/consolidation with dasatinib followed by blinatumomab in adults with newly diagnosed Ph-positive ALL, with molecular MRD as a central response measure. Single-arm (level 2). Long-term results: Foà et al., J Clin Oncol 2024 (PMID 38127722).

  • Level 1ALLpositive2024

    Blinatumomab for MRD-Negative Acute Lymphoblastic Leukemia in Adults (E1910)

    Litzow MR, Sun Z, Mattison RJ, Paietta EM, et al.. N Engl J Med. PMID 39047240. Flow-cytometry MRD; MRD-negative defined as <0.01% leukemic cells in bone marrow · n=224

    Phase 3 trial in adults 30-70 years with BCR::ABL1-negative BCP-ALL who had MRD-negative remission after induction/intensification. 224 MRD-negative patients were randomized 1:1 to 4 cycles of blinatumomab plus consolidation chemotherapy vs chemotherapy alone. At median follow-up 43 months, 3-year OS was 85% vs 68% (HR for death 0.41, 95% CI 0.23-0.73, P=0.002); 3-year RFS 80% vs 64% (HR 0.53, 95% CI 0.32-0.87). Level 1 (randomized, MRD-defined eligibility).

    Full text

  • Level 1ALLpositive2025

    Blinatumomab in Standard-Risk B-Cell Acute Lymphoblastic Leukemia in Children (COG AALL1731)

    Gupta S, Rau RE, Kairalla JA, Rabin KR, et al.. N Engl J Med. PMID 39651791. MRD used in COG risk assignment (standard-risk average or higher risk of relapse) · n=1440

    Phase 3 trial of children with newly diagnosed standard-risk B-cell ALL at average or higher risk of relapse, randomized to chemotherapy alone (n=722) or chemotherapy plus two nonsequential 28-day blinatumomab cycles (n=718). Interim analysis led to early termination of randomization. At median follow-up 2.5 years, estimated 3-year DFS was 96.0±1.2% vs 87.9±2.1% (P<0.001). Among average-risk: 97.5±1.3% vs 90.2±2.3%; among higher-risk: 94.1±2.5% vs 84.8±3.8%. Level 1 (randomized; MRD contributes to COG risk groups).

    Full text

CLL

AML

  • Level 2AMLpositive2016

    Assessment of Minimal Residual Disease in Standard-Risk AML (NPM1)

    Ivey A, Hills RK, Simpson MA, Jovanovic JV, et al.. N Engl J Med. PMID 26789727. RT-qPCR of NPM1-mutated transcripts in blood

    Persistence of NPM1-mutated transcripts in blood after the second chemotherapy cycle was present in 15% of patients and was associated with a greater 3-year relapse risk than absence of transcripts (82% vs 30%; HR 4.80, 95% CI 2.95-7.80, P<0.001) and lower survival (24% vs 75%; HR for death 4.38, 95% CI 2.57-7.47, P<0.001). MRD was the only independent prognostic factor for death in multivariate analysis (HR 4.84, 95% CI 2.57-9.15, P<0.001). Level 2. Foundational NPM1 MRD paper.

  • Level 2AMLpositive2020

    Impact of Conditioning Intensity of Allogeneic Transplantation for Acute Myeloid Leukemia With Genomic Evidence of Residual Disease

    Hourigan CS, Dillon LW, Gui G, Logan BR, et al.. J Clin Oncol. PMID 31860405. NGS genomic evidence of residual disease in blood before alloHCT (BMT CTN 0901)

    Among patients who were NGS-positive for residual disease before transplant, 3-year cumulative incidence of relapse was 19% with myeloablative conditioning (MAC) vs 67% with reduced-intensity conditioning (RIC) (P<.001); 3-year OS 61% vs 43% (P=0.02). In multivariable analysis of NGS-positive patients, RIC was associated with increased relapse (HR 6.38, 95% CI 3.37-12.10, P<.001), decreased RFS (HR 2.94, P<.001), and decreased OS (HR 1.97, 95% CI 1.17-3.30, P=0.01). Level 2 (MRD analysis of a randomized conditioning-intensity trial).

    Full text

  • ConsensusAMLpositive2021

    2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party

    Heuser M, Freeman SD, Ossenkoppele GJ, Buccisano F, Hourigan CS, Ngai LL, et al.. Blood. PMID 34724563. ELN-standardized flow and molecular MRD

    Updated 2018 ELN MRD recommendations: technical guidance for flow- and molecular-MRD, MRD thresholds, definition of MRD response, and how results should be reported and combined when several techniques are used. Consensus document (not a trial).

    Full text

  • Level 2AMLpositive2024

    Measurable Residual FLT3 Internal Tandem Duplication Before Allogeneic Transplant for Acute Myeloid Leukemia

    Dillon LW, Gui G, Ravindra N, Andrew G, et al.. JAMA Oncol. PMID 38696205. NGS FLT3-ITD MRD in first-CR blood before alloHCT (Pre-MEASURE / MEASURE consortium lineage)

    Cohort study of DNA sequencing on first-CR blood from adults with FLT3-ITD AML before allogeneic transplant, examining the association between pre-HCT MRD level and post-transplant relapse and death. Level 2. Part of the MEASURE / Pre-MEASURE genomic MRD program led by Hourigan and colleagues.

    Full text

  • Level 2AMLpositive2024

    Gilteritinib as Post-Transplant Maintenance for AML With Internal Tandem Duplication Mutation of FLT3 (MORPHO)

    Levis MJ, Hamadani M, Logan B, Jones RJ, et al.. J Clin Oncol. PMID 38471061. FLT3-ITD MRD pre- and post-HCT (prespecified subgroup) · n=356

    356 participants randomized post-HCT to gilteritinib or placebo. Overall RFS difference was not statistically significant (HR 0.679, 95% CI 0.459-1.005, two-sided P=0.0518). 50.5% had MRD detectable pre- or post-HCT; in this prespecified subgroup, gilteritinib was beneficial (HR 0.515, 95% CI 0.316-0.838, P=0.0065), while those without detectable MRD showed no benefit (HR 1.213, 95% CI 0.616-2.387, P=0.575). Level 2 (RCT with prespecified MRD subgroup; not MRD-guided randomization).

    Full text

  • Level 2AMLpositive2025

    Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML

    Levis MJ, Hamadani M, Logan BR, Jones RJ, et al.. Blood. PMID 39775763. FLT3-ITD MRD in the MORPHO trial · n=356

    Dedicated MRD analysis of post-transplant gilteritinib maintenance in FLT3-ITD AML, expanding the prespecified MRD interaction reported in the 2024 JCO primary paper. Level 2.

    Full text

  • Level 2AMLpositive2024

    Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission

    Othman J, Potter N, Ivey A, Jovanovic J, et al.. Blood. PMID 38364112. Postinduction molecular NPM1 MRD

    Postinduction molecular MRD in NPM1-mutated AML used to identify patients who benefit from allogeneic transplant in first complete remission. Level 2.

Lymphoma

  • Level 2lymphomapositive2018

    Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma

    Kurtz DM, Scherer F, Jin MC, Soo J, et al.. J Clin Oncol. PMID 30125215. CAPP-Seq ctDNA; early molecular response (EMR) and major molecular response (MMR) · n=217

    ctDNA dynamics from 217 patients at six centers, training and validation. Before therapy, ctDNA was detectable in 98%; pretreatment levels were prognostic in front-line and salvage settings. In the first validation set, front-line patients achieving EMR or MMR had superior 24-month EFS (EMR 83% vs 50%, P=0.0015; MMR 82% vs 46%, P<.001). EMR also predicted salvage 24-month EFS (100% vs 13%, P=0.011). Molecular response was independently prognostic including after adjustment for IPI and interim PET/CT. Level 2.

    Full text

  • Level 2lymphomapositive2025

    Remission Assessment by Circulating Tumor DNA in Large B-Cell Lymphoma

    Roschewski M, Kurtz DM, Westin JR, Lynch RC, et al.. J Clin Oncol. PMID 40802906. ctDNA MRD for remission assessment in LBCL

    ctDNA used to assess remission in large B-cell lymphoma, evaluating residual disease after therapy. Level 2. Complements earlier Kurtz 2018 work.

    Full text

  • Level 2lymphomapositive2026

    Prospective Validation of Circulating Tumor DNA Measurable Residual Disease After First-Line Therapy in Large B-Cell Lymphoma

    Wang S, Nijland M, Strobbe L, Oosterveld M, et al.. J Clin Oncol. PMID 41385760. PhasED-Seq ctDNA MRD at end of first-line therapy · n=136

    Prospective HOVON-902 cohort, curative-intent first-line treatment. Phased-variant identification successful in 134 of 136 (99%). At end of treatment, 83% were MRD-negative and 17% MRD-positive. 3-year PFS 17% vs 85% (HR 9.8, 95% CI 5.1-19, P=9.63×10^-12); OS 43% vs 92% (HR 7.7, 95% CI 3.4-17.4, P=1.27×10^-6). MRD positivity had higher PPV for 2-year PFS than positive PET (68% vs 56%, P≤.001); NPV similar (89% vs 88%). This is not a POLARIX analysis. Level 2.

    Full text

  • Level 2lymphomapositive2026

    Interim assessment by circulating tumor DNA in primary mediastinal large B-cell lymphoma: a multicenter LYSA study

    Camus V, Krzisch D, Bruscaggin A, Lévêque E, et al.. Blood Adv. PMID 41979332. Interim ctDNA in PMBCL (LYSA, NCT04980222)

    Multicenter LYSA study of interim ctDNA assessment in primary mediastinal large B-cell lymphoma. MRD detection after frontline therapy strongly complemented PET response criteria in predicting outcome. Level 2.

    Full text

  • Level 2lymphomapositive2026

    Circulating Tumor DNA Assessment of Disease Response in Large B-Cell Lymphoma: Lisocabtagene Maraleucel Versus Autologous Stem Cell Transplantation (TRANSFORM)

    Stepan L, Ansari S, Abramson JS, Okal A, et al.. J Clin Oncol. PMID 42044466. Ultrasensitive PhasED-Seq ctDNA at predefined time points · n=136

    Correlative ctDNA analysis of TRANSFORM (liso-cel vs salvage chemo + ASCT in second-line LBCL) in 136 patients. ctDNA clearance (MRD-neg) predicted longer EFS at all time points in both arms, with significantly more liso-cel-treated patients achieving MRD-neg. MRD-neg remained associated with EFS after adjusting for PET. Level 2.

    Full text

Other solid tumors

Level 3

Conference data

  • Level 3neutralAACR Annual Meeting 2026

    Abstract 3845: Enhancing MRD detection through an ultrasensitive ctDNA test: Insights from real-world clinical data

    Pyke, Rachel Marty · Abstract 3845 · more than 5,000 patients across 15 cancer types, as stated in the abstract (a single exact n is not given)

    NeXT Personal Dx (Personalis), bespoke panel of up to about 1,800 variants

    Median limit of detection across timepoints was 1.90 PPM (IQR 1.53-2.70) at a median cfDNA input of 12 ng. 45.3% of tests were ctDNA-positive. 40.2% of detections were below 100 PPM, and 14.7% of all detections were below 10 PPM. Among patients who became sustainably positive after a negative timepoint, 49% had a first MRD-positive result below 10 PPM. Two case examples (NSCLC and colorectal cancer) describe low-PPM detections that preceded imaging-confirmed recurrence. This is a real-world analytical and descriptive series, not a prospective outcomes trial.

Trial in progress