Waldenström’s Macroglobulinemia Precursor States: Could They be Key to a Cure?

On October 14th, 2020, the International Waldenström’s Macroglobulinemia Foundation (IWMF) hosted a webinar featuring Dr. Irene Ghobrial of the Dana Farber Cancer Institute. The focus of her presentation was on the precursor states of Waldenström’s macroglobulinemia (WM) and how changing the standards of care for them could potentially lead to significant advancements or even a cure for the disease. She also discussed two research studies being conducted by the institute, called PROMISE and PCROWD.

About Waldenström’s Macroglobulinemia (WM)

Waldenström’s macroglobulinemia, which is also known as lymphoplasmacytic lymphoma, is a rare type of blood cancer that affects two types of B lymphocytes, including plasma cells and lymphoplasmacytoid cells. A distinct characteristic of this type of cancer is the presence of a high concentration of IgM antibodies. It is a slow progressing form of blood cancer, and many patients can lead active lives. While it cannot be cured, it is treatable; some patients are able to experience years of remission without symptoms. There are only about 1,500 new cases per year in the U.S. Although it mostly occurs due to sporadic genetic mutations, a family history increases risk. Symptoms include vision loss, headaches, enlargement of the lymph nodes, liver, and spleen, bleeding nose and gums, weight loss, fatigue, and general weakness. To learn more about WM, click here.

What Are Precursor States?

Precursor states are pre-cancerous conditions in which the patient’s blood and immune system has started to undergo abnormal changes, but not to the extent that symptoms of cancer are present. Precursor states that can lead to WM include IgM monoclonal gammopathy of undetermined significance (MGUS) and smoldering WM (which is essential WM without symptoms).

Patients can live for a while (even a decade or more) in these precursor states without their disease progressing to WM; however, the risk of progression increases with time. The risk of progression is also affected by a variety of other factors, making it highly variable between individual patients. As an example, the presence of mutated MYD88 was linked to lower risk, whereas wild-type MYD88 was linked to higher risk.

While these states are generally considered ‘asymptomatic,’ in truth, many patients with IgM MGUS or smoldering WM may experience some changes as the function of their immune system is affected. Chronic infections are an issue for some patients.

But why talk about precursor states? After all, isn’t the standard of care for WM to ‘watch & wait’ until symptoms begin?

It’s true that watch & wait is the current advice if a patient isn’t experiencing active WM symptoms. However, Dr. Ghobrial thinks that some patients could benefit from earlier intervention. Unfortunately, there hasn’t been much research on this subject.

However, the Dana-Farber Institute has already begun delving into the complexities of these precursor states with the ongoing PCROWD and PROMISE studies.


PCROWD is for any adult patient that has been diagnosed with a precursor condition (including other forms outside of IgM MGUS and smoldering WM). This study aims to monitor as many 10,000 precursor patients. The research involves collecting samples of the bone marrow or blood in order to track changes over time. This can be done without the use of extra procedures and tests that are not already a routine part of care. The ultimate goal is to continue to identify potential biomarkers or risk factors that can predict the progression of the precursor state into full on WM or other blood cancers. Learn more about it here.


The PROMISE study is happening in tandem, and it is meant for people that are at a higher than normal risk of developing myeloma or related cancers. This includes African-Americans and the first degree relatives of diagnosed patients. Dana-Farber is looking for 50,000 volunteers between the ages of 40 and 75 years. These volunteers will be monitored for changes, once again with the goal of determining risk factors that predict the development of disease. Learn more about it here.

Ultimately, earlier treatment of precursor states could make a difference in outcomes, but the scientists need to understand more about them first before clinical trials can begin.

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