Research Strategy

The IWMF and its affiliates support the advancement of knowledge about the pathophysiological basis for the disease Waldenstrom’s macroglobulinemia (WM). This goal is accomplished by providing research grants for basic biomedical research into the origins, clinical manifestations, treatments, and potential future cures for WM.

Since the IWMF is a small non-profit foundation with limited resources and is funded almost entirely by individual members’ donations, our research strategy focuses on the financial support of programs and institutions that contribute to basic scientific research. The Foundation does not fund clinical trials.

IWMF-LLS Strategic Research Roadmap

Because of recent exciting advances in our understanding of the biological basis of WM, the IWMF decided in 2014 to update its research strategy and enlist the cooperation of many of the major players in the WM research community. To this end, the IWMF partnered with the Leukemia & Lymphoma Society (LLS) to sponsor a Strategic Research Roadmap Summit in New York City in May 2015. The conference agenda was divided into four major topics:

  • Signaling – What pathways do WM cells use for communication?
  • Immunology/immunotherapy – How can we better use our own immune system to fight WM?
  • Tumor microenvironment – How does the bone marrow/tumor environment affect WM cells?
  • “Omics” – What else can we learn about genomics, epigenomics, and mutations in WM cells?

To read more about the Summit and its participants click here. Dr. Stephen Ansell of the Mayo Clinic, scientific co-leader of the Roadmap Summit, discusses the four major topic areas on the Summit agenda in a short video entitled “An Exciting Time in Waldenstrom’s!”

As a result of the Summit, the IWMF-LLS Strategic Research Roadmap Initiative was developed to implement a robust research program to support the four focus areas above. Under the Roadmap Initiative, the IWMF will award Roadmap grants for 2-4 new research proposals each year, depending on funding availability. Each project shall be 2 years in length, at a cost of up to $200,000 per year per project.

The Foundation has a rigorous process in place for all research grant applications, which includes a review by an independent committee composed of selected members of Waldenstrom expert researchers via our RFP program. The proposals are ranked according to NIH review criteria and forwarded to the IWMF Board of Trustees. Generally speaking, at this stage a decision to fund a proposal is based on project quality and fund availability. Detailed information on the research grant application process can be found in Applying for a Research Grant.

A Request for Proposals (RFP) in response to the Research Roadmap is anticipated to be issued each year in the fall, with a deadline to receive RFP grant applications set for the following year in February. Notification of grant awards is made in June, with initial anticipated funding start dates from July-October. The following table lists the grant awards made to date as a result of the IWMF-LLS Strategic Research Roadmap Initiative:

Principal Investigator(s) Institution Project Title
2015-2016 Grant Award Recipients:
Dr. Madhav Dhodapkar Emory University, Atlanta, GA, USA, formerly of Yale University, New Haven, CT, USA Origins and immunotherapy of macroglobulinemia
Drs. Christian Buske, Jan Münch, and Daniel Sauter Ulm University, Ulm, Germany Characterization of endogenous CXCR4 inhibitory peptides to target Waldenström’s Macroglobulinemia
Dr. Marcel Spaargaren Academic Medical Center, Amsterdam, the Netherlands Towards a rational targeted therapy for Waldenström’s Macroglobulinemia by kinome-centered loss-of-adhesion and synthetic lethality screens
2016-2017 Grant Award Recipients:
Drs. Bruno Paiva and Jose Angel Martinez Climent Clinica Universidad de Navarra (CUN) and Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain Single-cell next-generation flow and sequencing to unravel the pathogenesis of Waldenström’s Macroglobulinemia and to design genetically-driven human-like experimental models
Dr. Marzia Varettoni Fondazione Italiana Linfomi Onlus (FIL), Alessandria, Italy Non-invasive diagnostics and monitoring of MRD [minimal residual disease] and clonal evolution in Waldenström’s Macroglobulinemia
Dr. Larry Kwak Beckman Research Institute of the City of Hope, Duarte, CA, USA Anti-tumor and immune microenvironment responses following a first-in-human DNA fusion vaccine for asymptomatic WM/LPL
Dr. Sherie Morrison University of California, David Geffen School of Medicine, Los Angeles, CA, USA Novel antibody-targeted interferons in combinatorial therapies for Waldenström’s macroglobulinemia
Dr. Shahrzad Jalali Mayo Clinic, Rochester, MN, USA Modulation of T-cell function by metabolomics signature of the bone marrow microenvironment in Waldenstrom’s Macroglobulinemia
2017-2018 Grant Award Recipients:
Drs. Steven Treon and Zachary Hunter Dana-Farber Cancer Institute, Boston, MA, USA Transcriptional characterization of untreated patients with Waldenstrom’s macroglobulinemia
Dr. Sherine Elsawa University of New Hampshire, Durham, NH, USA Epigenetic regulation of WM biology
2018-2019 Grant Award Recipients:
Dr. Yong Li Baylor College of Medicine, Houstin, TX USA Direct targeting the MYD88 L265P driver mutation in Waldenstrom’s macroglobulinemia
Dr. Constantine Mitsiades Dana-Farber Cancer Institute, Boston, MA USA CRISPR-based functional characterization of WM cells: insights into therapeutic vulnerabilities and strategies to overcome resistance
Dr. Marcel Spaargaren University of Amsterdam, Amsterdam, The Netherlands Towards a rational targeted therapy for Waldenström’s Macroglobulinemia by kinome-centered loss-of-adhesion and synthetic lethality screens
2019-2020 Grant Award Recipients:
Dr. Zachary Hunter Dana-Farber Cancer Institute, Boston, MA USA Multiomic Analysis of DNA, RNA and Epigenomic Networks for Prognostication and Novel Target Identification of Waldenstrom’s Macroglobulinemia
Dr. Ruben Carrasco Dana-Farber Cancer Institute, Boston, MA USA MYD88L265P Signaling-Associated Multiplex Characterization of the Bone Marrow Microenvironment in WM Patients for Clinical Application

Sponsorship of International Workshops on Waldenstrom’s Macroglobulinemia

As part of its commitment to furthering the advance of research specific to WM, the IWMF has been instrumental in the development and support of the biennial global conferences known as the International Workshops on Waldenstrom’s Macroglobulinemia(link is external), which provide biomedical professionals the opportunity to share their research findings and collaborate on methodologies. The Workshops are currently administered by the Bing Center for Waldenstrom’s Macroglobulinemia at Dana-Farber Cancer Institute.

Several important Consensus Panel Guidelines on diagnosis, front-line and relapsed treatment therapies, response assessment, and other important topics have emerged from these Workshops, with the goal of assisting physicians in their clinical care of WM patients.

Young Investigator Awards

To promote innovative research, the International Workshops on WM sponsor an award program for young medical specialists, researchers, and postdoctoral fellows specializing in the area of WM. The Young Investigator Awards (YIAs) are intended to develop knowledge and skills in WM, thereby stimulating research applicable to the development of medical innovations that save and sustain patients’ lives. The IWMF and several of its affiliates have contributed to the program by funding up-and-coming research investigators to attend the International Workshops on Waldenstrom’s Macroglobulinemia(link is external).

Applicants for the YIA program are expected to submit descriptions of ongoing research through an abstract submission. The Award includes a travel, hotel, and conference stipend as well as an on-site presentation of the award-winning research (oral and poster).

2016 YIA Awardees – IWWM9 in Amsterdam, The Netherlands

 
Awardee Abstract Title Institution Country Funding Organization
Constance Baer

 

MYD88 and CXCR4 analyses in lymphoplasmacytic lymphoma routine diagnostics need to consider mutations outside the L265P hotspot and follow-up testing MLL Munich Leukemia Laboratory, Munich Germany IWMF
George Chen

 

Acquisition of BTK C481S produces resistance to ibrutinib in MYD88 mutated WM and ABC DLBCL cells that is accompanied by ERK1/2 hyperactivation, and is targeted by the addition of the ERK1/2 inhibitor ulixertinib Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute USA IWMF
Eric Durot

 

Retrospective analysis of 56 cases of transformed Waldenstrom macroglobulinemia. A study on behalf of the French Innovative Leukemia Organization (FILO) Department of Hematology, Centre Hospitalier Universitaire de Reims France IWMF
Simone Ferrero

 

MYD88L265P mutation detection in Waldenström macroglobulinemia by droplet digital PCR: minimal residual disease monitoring and characterization on circulating free DNA Dept. of Molecular Biotechnologies and Health Sciences, Division of Hematology, University of Torino, Torino Italy IWMF
Maria Luisa Guerrera

 

Chromosome 6q deletions are common in Waldenström’s macroglobulinemia, and target regulatory genes for MYD88, CXCR4 and BCL2 signaling Fondazione IRCCS Policlinico San Matteo, Pavia Italy WM Italy
Joshua Gustine

 

The high risk for symptomatic hyperviscosity in patients with high serum IgM levels can be used to support initiation of treatment in Waldenstrom’s macroglobulinemia Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute USA IWMF
Shahrzad Jalali

 

Identifying a role for PD-1/
PD-L1/PD-L2 signaling in Waldenstrom’s macroglobulinemia
Mayo Clinic, Rochester USA IWMF
Lisa Kaiser

 

Characterization of endogenous CXCR4 inhibitory peptides to target Waldenstrom’s macroglobulinemia Institute of Experimental Cancer Research, University Hospital Ulm, Ulm Germany EWMn
Aneel Paulus

 

Creation of Waldenstrom macroglobulinemia digital avatars using machine-learning and systems biology algorithms exposes novel and clinically relevant therapeutic opportunities Mayo Clinic, Jacksonville USA IWMF
Nickolas Tsakmaklis

 

Mutated MYD88 homozygosity is increased in previously treated patients with Waldenstrom’s macroglobulinemia, and associates with CXCR4 mutation status Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute USA IWMF
Josephine M. Vos

 

Prevalence of MYD88 L265P mutation in IgM anti-MAG peripheral neuropathy Antonius Ziekenhuis Nieuwegein (AZN), Nieuwegein and UMC Utrecht The Netherlands IWMF

2014 YIA Awardees – IWWM8 in London, the United Kingdom

 
Awardee Abstract Title Institution Country Funding Organization
Jaimal Kothari

 

Initial experience and clinical utility of a high resolution melting assay to detect the MYD88 L265P in peripheral blood and bone marrow aspirates in patients with lymphoplasmacytic lymphoma and related disorders Department of Haematology, University College Hospital, London The United Kingdom WMUK
Julie Nielsen

 

MYD88 L265P: a target for T-cell based therapy of WM Deeley Research Centre, British Columbia Cancer Agency Canada WMF Canada
Jonas Paludo

 

Clinical features and survival outcomes of young patients with WM Mayo Clinic, Rochester USA IWMF
Eric L. Smith

 

CD19 targeted chimeric antigen receptor modified T-cells for the treatment of Waldenström’s macroglobulinemia Memorial Sloan Kettering Cancer Center USA IWMF
Vilhjálmur Steingrímsson

 

Population-based study on the impact of familial form of Waldenström’s macroglobulinemia on overall survival Department of Hematology, University of Iceland, Reykjavik Iceland EWMnetwork

 

Other Medical Conferences

The IWMF has exhibited at the Annual Meeting of the American Society of Hematology since 2001 and attends scientific presentations and poster sessions offered during the event. The Foundation sponsors an annual meeting of the IWMF Scientific Advisory Committee during ASH.

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