Select MRD highlights from ASCO, EHA, and ICML 2025
Minimal residual disease (MRD) is playing an increasingly pivotal role in clinical decision making across hematologic malignancies. At ASCO, EHA, and ICML 2025, new data showcased how MRD assessment—enabled by highly sensitive and standardized tools such as clonoSEQ®—are being used to guide treatment duration, evaluate consolidation strategies, and differentiate the efficacy of emerging regimens. These studies reflect a growing shift toward MRD-informed care, where real-time insights into disease clearance are helping clinicians tailor therapy with greater precision.
The most relevant studies and data shaping current understanding and clinical application of MRD are highlighted.
Non-Hodgkin’s lymphoma
The clonoSEQ DLBCL assay (ctDNA) tracks disease clearance and high rates of EOT MRD negativity in DLBCL patients treated with newer regimens.
Meaningful rates of false positives using phased variants assessment require further clarification.
Multiple myeloma
Achievement of deep, post-induction MRD responses with clonoSEQ can inform treatment decisions for consolidation.
Consistent achievement of deep and sustained MRD negativity rates supports quadruplet regimens as a new standard of care for NDMM patients.
Chronic lymphocytic leukemia
clonoSEQ identified clearance of disease at thresholds <10-5 to tailor the duration of venetoclax therapy.
Non-Hodgkin’s lymphoma
Initial phase 2 readout:
clonoSEQ assay characterizes ctDNA clearance treatment following treatment with glofitamab plus pola-R-CHP
Primary objective
Evaluate the efficacy of adding glofitamab to pola-R-CHP using the clonoSEQ DLBCL assay (ctDNA)
Key results
Eighteen of 27 patients were MRD-negative (ctDNA) by C4D1, while nine were MRD-positive:
- Six patients converted from MRD-positive to MRD-negative status after the addition of glofitamab after C2.
Among 20 patients with MRD testing at EOT:
- Nineteen were MRD-negative and still in remission (median follow-up of 8.7 months).
- One MRD-positive patient was still in CR.
Implications
High rates of MRD negativity assessed by the enhanced clonoSEQ DLBCL assay (ctDNA) were observed following the addition of glofitamab to pola-R-CHP.
The conversion of some patients to MRD negativity after adding glofitamab indicates the potential to use MRD status to identify higher-risk patients who may benefit from additional therapy.
Study design
Key MRD findings
Patients with MRD conversion at EOT
A multicenter phase II study of glofitamab plus polatuzumab-R-CHP for patients with high-risk diffuse large B-cell lymphoma. Crombie JL, et al.
DIRECT: translation sample collection study:
Insights into the sensitivity of phased variant ctDNA assays in DLBCL
Primary objective
Validate the application of a phased variant ctDNA assay in a cohort of DLBCL patients
Key results
MRD status, using a bespoke ctDNA assay that analyzes phased variants, is prognostic for outcomes.
- From EOT, the two-year PFS rate was 95% for MRD-negative patients vs. 39% for MRD-positive patients.
- The recurrence rate among MRD-negative patients was low, but there were a meaningful number of MRD-positive patients who didn’t relapse.
Implications
Why some MRD-positive patients did not relapse is not fully understood but may be related to short follow-up duration or identification of phased variants from indolent precursor disease.
LOD95 is a variable and patient-specific metric. While phased variant assays have demonstrated an analytic LOD of <1 ppm, individual patients rarely achieve an LOD95 of <1 ppm with standard plasma volumes.
Study design
DIRECT was a prospective, multi-site study assessing the feasibility and utility of ctDNA in 188 patients with aggressive B-cell non-Hodgkin’s lymphoma. The utility of this ctDNA assay was evaluated in three applications: 1) pre-treatment risk prediction, 2) baseline genetic profiling, and 3) MRD response assessment at EOT.
Patients with MRD conversion at EOT
LOD95 by sample type and timepoint
The DIRECT study: a roadmap for ctDNA-based risk prediction, molecular profiling and MRD detection in diffuse large B-cell lymphoma. Krupka JA, et al.
Multiple myeloma
MIDAS phase 3 study:
MRD-guided consolidation following Isa-KRd induction demonstrated
MRD-negative patients can forgo upfront transplant without compromising depth of response
- Achievement of deep, post-induction MRD responses with clonoSEQ can inform treatment decisions for consolidation.
- Consistent achievement of deep and sustained MRD negativity rates supports quadruplet regimens as a new standard of care for NDMM patients.
Primary objective
Evaluate MRD-guided consolidation strategies following six cycles of Isa-KRd
Key results
- ASCT consolidation did not improve MRD negativity rates (primary endpoint) in MRD-negative patients post-induction.
- The MRD negativity rate (10-6) was 84% in the Isa-KRd cohort and 86% in the ASCT cohort.
- Tandem transplant did not improve MRD negativity rates (primary endpoint) in MRD-positive patients post-induction.
- The conversion rate to MRD-negative status (10-6) was 40% in the single transplant cohort and 32% in the tandem transplant cohort.
Implications
MIDAS was the first randomized controlled trial with an MRD-directed approach to demonstrate that MRD-negative patients can safely forgo upfront transplant without compromising depth of response.
Study design
Minimal residual disease adaptive strategy: frontline therapy for patients eligible for autologous stem cell transplantation less than 66 years; a prospective study
Key MRD findings
MRD-driven strategy following Isa-KRd induction in transplant-eligible NDMM: Primary endpoints of the phase 3 MIDAS trial. Perrot A, et al.
PERSEUS phase 3 update:
Patients who had achieved sustained MRD negativity ≥12 months (<10-5) had superior outcomes, regardless of treatment
Primary objective
Evaluate the impact of sustained MRD negativity on PFS
Key results
Sustained MRD negativity (10-5) rates were higher in the Dara-VRd arm relative to the VRd arm of the study.
- The ≥12 months rate was 64.8% for patients treated with Dara-VRd vs. 29.7% for VRd-treated patients.
The ≥24 months rate was 55.8% for patients treated with Dara-VRd vs. 22.6% for VRd-treated patients.
PFS outcomes were similar for patients who achieved sustained MRD negativity in both treatment groups.
Implications
Consistent with other studies evaluating regimens containing anti-CD38 antibodies, upfront treatment with a quadruplet regimen containing daratumumab resulted in higher rates of sustained MRD negativity relative to TE-NDMM patients who didn’t receive a quadruplet.
Patients who achieve sustained MRD negativity ≥12 months (<10-5) have superior outcomes, regardless of treatment.
Study design
Key MRD findings
PFS by sustained MRD-negativity (10-5) ≥CR status
≥12 months
Sustained MRD negativity (10-5) ≥CR status
≥12 months
IsKia phase 3 update:
Sustained MRD negativity at a threshold of 10-6 differentiates quadruplet efficacy
Primary objective
Compare the rates of sustained MRD negativity between the Isa-KRd and KRd arms of this study
Key results
One-year sustained MRD negativity rates were higher in the Isa-KRd arm of the study at sensitivity thresholds of 10-5 and 10-6.
- The rate in the Isa-KRd arm was 66% at 10-5 (52% at 10-6).
- The rate in the KRd arm was 59% at 10-5 (38% at 10-6).
Implications
Achievement of sustained MRD negativity was associated with prolonged PFS and OS.
Consistent with other studies evaluating regimens containing anti-CD38 antibodies, upfront treatment with a quadruplet regimen containing isatuximab resulted in higher rates of sustained MRD negativity relative to patients who did not receive a quadruplet.
MRD assessment at a 10-6 threshold demonstrated markedly different MRD negativity rates than at 10-5.
Study design
Key MRD findings
One-year sustained MRD negativity rate (10-5) [ITT analysis]
ADVANCE phase 3 initial readout:
Primary MRD endpoint supports differentiation of treatment
response associated with newer regimens in multiple myeloma
Primary objective
Evaluate the relative efficacy of Dara-KRd vs. KRd in NDMM, independent of transplant eligibility
Key results
MRD negativity rate (<10-5) at the end of induction—the primary endpoint—was significantly higher among patients treated with Dara-KRd compared to those treated with KRd alone.
- 59% of patients in the Dara-KRd arm were MRD-negative.
- 33% of patients in the KRd arm were MRD-negative.
Implications
This study reinforces data from other studies supporting use of a quadruplet regimen for frontline treatment of NDMM patients.
This study design included directing MRD-positive patients to receive a post-induction transplant. Future data will provide additional insight into MRD-guided treatment decisions in this setting.
Study design
Key MRD findings
Primary endpoint: MRD-negative 10-5 in ITT population
Randomized, multi-center study of carfilzomib, lenalidomide, and dexamethasone with or without daratumumab in patients with newly diagnosed multiple myeloma: The ADVANCE clinical trial. Landgren CO, et al.
Chronic lymphocytic leukemia
VenetoSTOP phase 3 initial readout:
MRD-guided discontinuation of venetoclax in CLL
Primary objective
Evaluate venetoclax treatment duration as guided by peripheral blood MRD status
Key results
Approximately 50% of patients who discontinued venetoclax did not convert to MRD-positive status within two years.
- The median MRD5-free survival rate was 71% at 12 months and 46% at 24 months.
Overall PFS was 84% at 24 months, consistent with other studies in which venetoclax was discontinued.
Implications
High PFS rates and overall durability of MRD-free remission post-discontinuation support the use of MRD to tailor the duration of venetoclax.
These data add to the growing body of literature demonstrating MRD assessment at levels <10-5 to guide treatment decisions.
Study design
Key MRD findings
Time to dMRD5
To learn more, contact mrdbiopharma@adaptivebiotech.com.
ASCO: American Society of Clinical Oncology annual meeting; ASCT: autologous stem cell transplant; BM: bone marrow; BMA: bone marrow aspirate; C: cyclophosphamide; C(#): cycle number; CI: confidence interval; CLL: chronic lymphocytic leukemia; CR: complete response; ctDNA: circulating tumor DNA; D(#): day number; D and Dara: daratumumab; d: dexamethasone; DLBCL: diffuse large B-cell lymphoma; dMRD5: detectable minimal residual disease ≥10-5; EHA: European Hematology Association annual meeting; EOT: end of treatment; FFPE: formalin-fixed, paraffin-embedded; H: doxorubicin; HR: hazard ratio; ICML: International Conference on Malignant Lymphoma; ID: clonality test; Isa: isatuximab; ITT: intention to treat; K: carfilzomib; LN: lymph node; LOD95: limit of detection with 95% probability; MRD: minimal residual disease; MRD+: minimal residual disease positive status; MRD-: minimal residual disease negative status; MRD5-free survival: period of time that patients have undetectable MRD at a threshold of 10-5; NDMM: newly diagnosed multiple myeloma; NGS: next generation sequencing; OR: overall response; OS: overall survival; P: prednisone; PB: peripheral blood; PET: positron emission tomography; PFS: progression-free survival; pola: polatuzumab; ppm: parts per million; PD: progressive disease; PR: partial response; lenalidomide or rituximab; sCR: sustained complete response; SLL: small lymphocytic lymphoma; TE: transplant eligible; uMRD: undetectable minimal residual disease; V: bortezomib; ven: venetoclax; VGPR: very good partial response.
clonoSEQ® is available as an FDA-cleared in vitro diagnostic (IVD) test service provided by Adaptive Biotechnologies to detect measurable residual disease (MRD) in bone marrow from patients with multiple myeloma or B-cell acute lymphoblastic leukemia (B-ALL) and blood or bone marrow from patients with chronic lymphocytic leukemia (CLL). Additionally, clonoSEQ is available for use in other lymphoid cancers and specimen types as a CLIA-validated laboratory developed test (LDT). To review the FDA-cleared uses of clonoSEQ, visit clonoSEQ.com/technical-summary.