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.
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|
|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|
|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|
|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|
|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|
|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|
|Identifying a role for PD-1/
PD-L1/PD-L2 signaling in Waldenstrom’s macroglobulinemia
|Mayo Clinic, Rochester||USA||IWMF|
|Characterization of endogenous CXCR4 inhibitory peptides to target Waldenstrom’s macroglobulinemia||Institute of Experimental Cancer Research, University Hospital Ulm, Ulm||Germany||EWMn|
|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|
|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|
|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|
|MYD88 L265P: a target for T-cell based therapy of WM||Deeley Research Centre, British Columbia Cancer Agency||Canada||WMF Canada|
|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|
|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.