Residual disease assessment in hematologic malignancies to improve patient-relevant outcomes across Europe (RESOLVE)
Principal investigator: Patrizio Armeni
Team UB/Cergas: Patrizio Armeni, Francesco Costa, Oriana Ciani, Carla Rognoni (CeRGAS)
Partners: Medizinische Hochschule Hannover - MHH (Coordinator); Stichting VUMC; European Research Initiative on CLL e.V.; Istituto Romagnolo per lo Studio e la Cura dei Tumori “Dino Amadori” (IRST); ELN Foundation (ELN); Fundación Instituto de estudios de ciencias de la salud de Castilla y Leon (IESCYL-IBSAL); German Cancer Research Center (GCRC); ORTEC Optimization Technology BV (ORT); Università Commerciale Luigi Bocconi (UB); Universitá degli studi di Roma Tor Vergata (UNITOV); Universität Ulm (UULM); Technische Universität Dresden (TUD); Hellenic Society of Haematology (HSH); Shaare Zedek medical center (Shaare Zedek); Copernicus Memorial Hospital in Lodz Comprehensive Cancer Center and Traumatology (Szpital Kopernika w Łodzi); Istituto di Ricerche Farmacologiche Mario Negri (MNEGRI); Charite Berlin, German Biobank Alliance (GBN); Fondazione GIMEMA; FlowView Diagnostics BV (FlowView); French Innovative Leukemia Organization (FILO); Ostdeutsche Studiengruppe Hämatologie und Onkologie e.V. (OSHO)
Sponsor: European Union's Horizon Europe Research and Innovation Action “Pragmatic clinical trials on minimally invasive diagnostics” (Call HORIZON-MISS-2023-CANCER-01-03)
Duration: 54 months starting from January/April 2024
Abstract:
Acute myeloid leukemia (AML) is the most common acute leukemia in adults with increasing incidence over time. It is the most aggressive leukemia subtype, with a 5-year overall survival (OS) of only 28% overall. Chronic lymphocytic leukemia (CLL) is the most common chronic leukemia in adults. Survival is generally good (80% and higher at 5 years for many populations) thanks to effective targeted therapies, but it is often unclear when to stop treatment. For both AML and CLL, consolidation therapy is typically provided after initial response-inducing treatment with the intention of preventing disease progression or relapse. Unfortunately, these consolidation therapies are costly in terms of the associated health risks, quality of life (QoL), and the financial burden on patients, caregivers, and health care systems.
Measurable residual disease (MRD), evaluated using the sensitive technique of multi-color flow cytometry (MFC) or qPCR, has been shown to be a valuable prognostic tool for patients with acute and chronic leukemias, anyway, MRD assessment is not established as a treatment-guiding intervention in the most frequent acute and chronic leukemias in adults, namely AML and CLL. Mounting evidence suggests that MRD-negative AML and CLL patients – those with residual disease below a certain detection limit following initial treatment – may be at a lower risk for relapse, even without intensive or prolonged consolidation therapy. In these cases, treatment intensity might be safely reduced thus reducing their side effects and economic burden and thereby increase QoL.
The planned study will establish the predictive value of MRD in AML and CLL patients and will assess the cost-effectiveness of using MRD testing to guide treatment decisions.
To identify MRD-negative AML and CLL patients in a uniform and reproducible way, a harmonized MRD assessment will be implemented across Europe, building on the MRD testing infrastructure in place in many countries for other leukemias. In parallel, a patient registry for AML and CLL patients will be implemented from which participants can be recruited for a randomized, controlled pragmatic trial (RCPT). This trial will prove the effectiveness of reducing treatment intensity in MRD-negative AML and CLL patients in a real-world setting.