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Research & Trials

 

Molecular Research

By combining clinical and translational research efforts, the consortium aims to advance our knowledge of the molecular and cellular biology of WM. This multidisciplinary approach is critical for tackling complex diseases like WM and holds promise for a better understanding of the underlying conditions.

Our research goals seek to understand WM comprehensively, addressing various disciplines and approaches such as genetics and epigenetics to microenvironment interactions and minimal residual disease detection.  All these efforts pursue the final goal to translate these findings into a better clinical care of WM patients.

 

 Plasma cell dyscrasias unit Department of Clinical Therapeutics School of Medicine, National and Kapodistrian University of Athens

Greece, Athens

Despina FotiouPlasma cell dyscrasias unit Department of Clinical Therapeutics School of Medicine, National and Kapodistrian University of Athens

 

The Department of Clinical Therapeutics/ Plasma Cell Dyscrasia Unit is a reference center  for the diagnosis and treatment of plasma cell/lymphoproliferative neoplasms in Athens, Greece. A large biobank has been developed in our Department providing various types of material for our translational research. Current research in WM mainly focus on translational and clinical research  projects.  Our laboratory is extensively working on circulating tumor DNA from the peripheral blood, initially  for the detection and characterization of the mutational status of MYD88 and CXCR4. Further, we are working on optimizing ultra-sensitive cost-effective techniques based on real time PCR that can detect the MYD88 L265P mutation even when expressed at very low copies in peripheral blood.  Using sequential peripheral blood sampling we are developing techniques for tumor fraction and mutational burden assessment based on circulating tumor DNA, to understand and predict treatment resistance to current therapies. Along the same lines, we are also developing techniques for the isolation of circulating tumor cells and further single cell analysis. Through and extensive collaborative network in Greece, Europe and USA  we are also focusing in the biology of early lesions and the  investigation of the microenvironment of the bone marrow in these patients and their symptomatic counterparts.

 Prospective Evaluation of Minimal Residual Disease in WM across Different Tissues and Treatments

Results of the BIO-WM Trial of the Fondazione Italiana Linfomi (FIL)

(M. Ferrante, S. Ferrero, Torino, Italy)

 

Introduction. MYD88L265P is the hallmark mutation in Waldenström Macroglobulinemia (WM) and is becoming increasingly important in the management of IgM-gammopathies, due to its role as prognostic and predictive biomarker. Recently, MYD88L265P detection by allele-specific quantitative PCR was proposed as reliable minimal residual disease (MRD) marker in bone marrow (BM) samples (Varettoni, Hematol Oncol 2022). Novel, more sensitive, techniques as droplet digital PCR (ddPCR) might extend the feasibility of MRD detection in WM also in non-invasive tissues, as peripheral blood (PB) or plasmatic cell-free (cf) DNA. This was a secondary endpoint of the multicenter, observational “BIOWM  (NCT03521596) trial, sponsored by the Fondazione Italiana Linfomi (FIL) and the International WM Foundation/Leukemia and Lymphoma Society. From 2018 to 2020 this trial enrolled 300 consecutive patients with primary diagnosis of WM or IgM-MGUS and a systematic biobanking was performed. Here are presented the first results of the MRD study on the patient subset who received frontline treatment, with the aim of driving correlations with clinical response, type of therapy received and outcome prediction. 
 

 Real-world treatment outcomes in the global Waldenström’s Macroglobulinemia patient-derived data registry, WhiMSICALross Different Tissues and Treatments

Sydney, Australia

(Ibrahim Tohidi-Esfahan, Judith Trotman)

 

WhiMSICAL (Waldenström’s Macroglobulinemia Study Involving CArt-wheeL) is the first global Waldenström’s Macroglobulinemia (WM) registry capturing patient-derived data to complement clinical trials data in this rare cancer (Tohidi-Esfahani et al, Am J Hematol 2021). The registry was interrogated for treatment outcomes of chemoimmunotherapy (CIT) compared to Bruton tyrosine kinase inhibitors (BTKi).

 

 

 

Clinical Trials