MeMeasurable residual disease (MRD) detected by multiparameter flow cytometry (MFC) has strong prognostic value in patients with the most frequent acute and chronic leukemias, acute myeloid (AML) and chronic lymphocytic leukemia (CLL), but it has not yet been confirmed as a treatment-guiding biomarker. The RESOLVE Consortium will leverage numerous existing expert networks and patient advocacy partnerships to establish the predictive value of MRD in AML/CLL patients, with the expectation that this affordable, minimally-invasive biomarker can be imminently used to guide the intensity of consolidation therapy, improve quality of life (QoL), and reduce costs. This will be achieved through 1) development of a real-world patient registry and data platform; 2) establishment of standardized, decentralized MRD analysis across Europe; and 3) a randomized, controlled multi-national pragmatic trial based on the hypothesis that treatment intensity can be safely reduced in MRD negative AML/CLL patients, to provide evidence for the clinical, personal and societal impact of MRD-guided therapy. These efforts will be supported by RESOLVE’s participatory research pipeline, which will incorporate input from patients, caregivers, and experts in social sciences and health economics. The real-world nature of the study ensures broadly applicable results for all patients regardless of location, socioeconomic status, gender, sex, disability or ethnicity. The findings will then be effectively communicated and disseminated following open science principles through the medical community for uptake in routine clinical practice. The laboratory, clinical, and patient advocacy infrastructures already in place will support rapid adoption of MFC-based MRD assessment to aid in clinical decision-making. The Consortium’s widespread member organizations will work with policymakers and authorities across the EU to provide access to the test in the national health care systems for all AML and CLL patients. This action is part of the Cancer Mission cluster of projects "Diagnostics and Treatment (diagnostics)".

In IMPACT-AML, a multidisciplinar R/R AML represents a model of high-impact disease, in which no standard of care exists, and where we have an urgent need for new evidence on possible therapies; AML offers the setting in which methodological innovation will combine powerful instruments of clinical trials with personalized medicine through academic efforts. Hereby, we propose to create an inclusive master framework for relapsed or refractory acute myeloid leukemia (STREAM) to include patients with R/R AML across Europe proficiently acquire an unselected population for clinical trials and monitor outcomes including neglected cohorts. Thereafter we will conduct a prospective randomized pragmatic clinical trial (RPCT) that will compare the classical “high intensity” rescue chemotherapy with biology-driven, “low intensity” rescue to obtain “real world” data on the benefit of one of the two different strategies in term of survival also considering patients and caregivers preferences, patient-reported outcomes (PRO), accessibility, affordability, and social cost. RPCT will aim to evaluate the effectiveness of real-world clinical alternatives in routine care. In addition to retaining the high internal validity of traditional randomized trials, it will maximize external validity, i. e. generalizability of results to many settings. In this context, the inclusion of an RPCT in the master framework will allow a dynamic inclusion and the collection of the excluded population as an instrument to predict the real-life applicability of clinical trial results. We will offer Europe results from an ambitious project, that will go beyond the state of the art in R/R AML demonstrating the superiority of a strategy in a first-of-his-kind clinical trial, providing strong data that will be delivered to national health care providers, policymakers, and health authorities data on optimized and affordable treatment for R/R AML and promoting the implementation of the selected better option. This action is part of the Cancer Mission cluster of projects on ‘Diagnosis and treatment’.