A look at current WM research and how your donations are put to work
Here’s a quick snapshot of current areas of WM investigations discussed at the International Workshop on WM held at Madrid in 2022. Two WMFC assisted projects are also included.
In addition to the science our research snapshot also includes a ‘soft’ research project about an issue that we as patients all have to deal with – what do we want from our treatments?
The WM research landscape is changing
Research continues to seek out what causes our B cells to tip over the edge and become WM cells. However it’s becoming increasingly obvious there’s so much going on within our cells that it’s unlikely that any single event will emerge as the culprit.
What makes WM tick?
The WM mechanisms are linked not just to our DNA but our RNA too. Dr. Paludo focused on long pieces of RNA inside cells that do not encode proteins but, instead, act as regulators of cell function. Dr. Paludo reported a number of these lncRNAs that may be involved in WM.
When genes go awry
When the genes are mutated or fail to operate, the normal control is released and malignant cells grow more easily. Investigation into a gene called TP53 received prominent attention recently.
A new view of our immune system
An increasingly recognized area of WM research is the role of the immune system within the bone marrow in controlling WM growth.
For instance there’s a T regulatory cell (Treg) in bone marrow that suppresses other T cells so that they are less able to control the WM cells. Researchers are looking at how these Tregs interact with the WM cells through a pair of signaling molecules called CD40 and CD40L.
There’s another type of bone marrow cell that also suppresses the body’s immune reaction to WM cells. These cells are called myeloid-derived suppressor cells. In the bone marrow of WM patients, these suppressor cells are more numerous, more activated, and are capable of interfering with how normal T cells kill WM tumor cells. Researchers are looking at drugs that interfere and inhibit their action.
New treatment directions
Dr. Ken Anderson of Dana-Farber discussed bispecific antibodies that grab on to a tumor cell (in this case, a WM cell) with one arm and a T cell with the other arm. This brings the two cells—the WM cell and the T cell— closely together to allow the T cell to kill the tumor cell.
Dr. Shayna Sarosiek from Dana-Farber discussed antibody-drug conjugates. These consist of an antibody targeted specifically to a protein on the surface of B cells (including WM cells), linked to a highly potent drug. After attaching, the antibody-drug conjugate is taken into the cell, where the drug is released and kills the cell.
Research supported by funding from the WMFC
At Dana Farber in Boston we supported a very sophisticated search for new research directions – “Multiomic Analysis of DNA, RNA and Epigenomic Networks in WM”. The results have been promising and will permanently change our understanding of the biology, subtypes and progression of WM.
At the Sunnybrook Cancer Research Institute in Toronto, Dr. Neil Berinstein is the principal investigator for the BRAWM trial. This clinical trial studies combining the standard-of-care Bendamustine + Rituximab with a BTK inhibitor, Acalabrutinib.
Again in Toronto, Dr. Signy Chow’s gene panel study is using BRAWM study samples.
Specifically, she is examining how the genes of WM cells change with time, starting with cells of patients before they have ever been treated and then examining their cells during treatment. This study of how cancer cells change while under treatment is called “genomic clonal evolution.”
A different path of research – talking to WMers.
Not all research focuses on WMers inner cellular workings. There are other ‘softer’ issues which often affect us quite directly but that we may not have considered or be aware of.
A recent Dutch study – the WM-Voice project – looked at patient preferences regarding treatment options for Waldenström’s macroglobulinemia. However until this study, the treatment preferences of WM patients had not been assessed.
Most patients look for the treatment that offers the best efficacy – the longest progression-free period. But there are many other patient considerations – which has the least side-effects?
Do I want chemo or targeted therapy?
Pills versus intravenous?
A fixed duration of treatment or an ongoing treatment?
So what do patients want?
Not surprisingly, patients want the best efficacy – the longest progression-free period.
They want the treatment with the least side effects.
WM patients preferred a treatment with a low risk of a future secondary malignancy.
Patients wanted to avoid “adverse events” of which neuropathy was top of the list.
And patients preferred a fixed duration intravenous/subcutaneous treatment over an ongoing oral treatment.
Finally, they preferred a regimen with targeted therapy as opposed to chemotherapy.
Unfortunately, the combination of these properties does not match a currently available treatment regimen. However, these patient preferences describe a good, well-defined target so the results of this study will certainly inform future drug design.
New paths to explore – the future of WM research
WM is a complicated condition so we’re also helping the search for new avenues for research scientists to explore. The WMFC attended the recent IWMF Scientific Review Committee meeting, where a team of international WM researchers evaluated numerous funding grant requests. Only the top few will be funded and the WMFC will conduct a separate evaluation of the accepted proposals to determine our level of participation.
We have also finalized a partnership agreement with the Lymphoma and Leukemia Society of Canada to jointly fund a two year, $200,000 grant to search for and approve funding for Canadian WM research.
There are generally several WM-related international research projects underway so many avenues are being explored. Additionally, research into lymphomas and leukemias can also be relevant to WM and vice versa. Some paths will lead to further progress but others will come to nothing. But it all adds to the sum total of WM learning though.
We’ve yet to see the full effect of specialist AI systems on WM research but it’s reasonable to expect an advance in the pace of progress and an increase in its directions. New treatments might emerge from banks of database servers rather than labs.
Our goal for the future is to increase our research funding by tripling our revenues. The WMFC Board has been active recently seeking funding from charity support Foundations across Canada. We’ve been quite successful – in March we received a significant donation from Fondation Mirella & Lino Saputo in Quebec. We also received a generous donation from the Robert A. & Maria Bailey Fund at the Edmonton Community Charity.
Drs. Josephine M. I. Vos and Karima Amaador, Department of Hematology, Amsterdam University Medical Center (UMC), The Netherlands. Amaador et al., “Patient preferences regarding treatment options for Waldenströms macroglobulinemia: A discrete choice experiment.” Cancer Medicine, https://doi.org/10.1002/cam4.5080, 2022