The 67th Annual Meeting of the American Society of Hematology, held in December, was an outstanding showcase of research. To kick off the year, we’re taking a look back, with a special focus on our oral presentations.
On today’s post, we’d like to highlight Dr. Jesse Tettero’s abstract, “Validation of measurable residual disease as a surrogate endpoint in acute myeloid leukemia: A HARMONY Alliance study of European randomized trials.”.
Interview with Dr. Jesse Tettero
A few days ago, we had the privilege of interviewing Dr. Jesse Tettero about his outstanding research and contributions to the validation of measurable residual disease as a key endpoint in acute myeloid leukemia. We’re sharing it with you here and hope you enjoy it.
How This Research Is Shaping the Conversation
The HARMONY Alliance Foundation is not alone in recognising the value of this research. Leading scientific outlets, including Cancer Network and Springer Medicine, have published articles highlighting its importance for the future of leukaemia treatment. Below is a non-exhaustive list of coverage related to this work:
- Ecancer https://ecancer.org/en/video/12659-mrd-validated-as-a-surrogate-endpoint-for-survival-in-aml
- Hematoinfo: https://www.youtube.com/watch?v=CIwO5FSiN84
- Cancer Therapy Advisor: https://www.cancertherapyadvisor.com/reports/mrd-credible-surrogate-endpoint-acute-myeloid-leukemia/
- ASH Press relases: https://www.hematology.org/newsroom/press-releases/2025/advances-in-technology-help-improve-safety-and-access-to-blood-cancer-therapies
- CancerNetwork: https://www.cancernetwork.com/view/mrd-may-predict-survival-in-induction-chemotherapy-aml-trials
- Springer Medicine: https://www.springermedicine.com/acute-myeloid-leukemia/ash-2025/harmony-confirms-mrd-as-a-robust-surrogate-endpoint-in-aml/51809966
- Oncology News Central https://www.oncologynewscentral.com/multiple-myeloma/investigational-in-vivo-car-t-potential-game-changer-in-myeloma
Summary of the abstract
Measurable residual disease (MRD) refers to the small number of cancer cells that remain in the body after a patient has achieved remission. It is a key biomarker in hematology, fundamental for evaluating the efficacy of therapies, and increasingly important in informing regulatory decisions.
In multiple myeloma, MRD has recently been accepted by the U.S. Food and Drug Administration (FDA) as a co-primary endpoint—that is, a biomarker that can, in practice, be considered equivalent to the conventional primary endpoint, overall survival (OS). This recognition allows the regulatory process, including drug approval, to be accelerated, as MRD can serve as a surrogate endpoint where previously only OS could be used. Consequently, treatments can be more precisely tailored, improving patient outcomes. However, this approach has not yet been widely adopted in acute myeloid leukemia (AML).
Although post-chemotherapy MRD positivity is linked to poor prognosis in AML, its routine assessment is limited by the heterogeneity of the disease and the lack of trial-level validation. This gap motivated Dr. Jesse Tettero and his team to investigate MRD’s prognostic value in a rigorously standardized manner.
To this end, they created a database of 1,858 adult AML patients enrolled in trials conducted by AMLSG, HOVON-SAKK, SAL, and UK-NCRI. Eligible trials involved randomization to either an experimental therapy or placebo, added to a standard intensive induction chemotherapy backbone. MRD was assessed prior to consolidation therapy using either multiparameter flow cytometry (MFC) or quantitative PCR (qPCR) for NPM1. All data were harmonized using the OMOP common data model for consistent analysis.
The findings were substantial. MRD positivity was associated with significantly worse OS across the cohort, and this association remained consistent when stratified by treatment arm (placebo vs. experimental). The global odds ratio (OR) for the association between MRD status and survival endpoints was 0.39, indicating a strong prognostic effect. These results were robust across patient subgroups, including different mutational profiles, transplant status, and across multiple trials.
These findings support the use of MRD as an intermediate endpoint in intensively treated AML patients. As MRD-guided therapy becomes standard practice, this harmonized dataset provides timely evidence to support MRD as a regulatory surrogate endpoint, facilitating data sharing, fostering collaboration, and ultimately improving patient care.