Change the 'Asymptomatic' Label for Rare Lymphoma Status

Pam Harrison

October 10, 2019

Patients in the early stages of Waldenstrom macroglobulinemia (WM), a rare type of non-Hodgkin lymphoma, are usually followed with observation rather than offered treatment and are labeled "asymptomatic."

But this label is inaccurate because many "asymptomatic" patients are not free of symptoms, they just don't have the right kind of symptoms to warrant an intervention.

This is the argument put forward by a physician who is also a patient.

"I am a patient with WM, and it was 3 years from the time of my diagnosis until I needed treatment," says Frederick Leonard, MD, MPH, from the International Waldenstrom's Macroglobulinemia Foundation in Sarasota, Florida.

"At no time during that period was I asymptomatic," he adds. "Based on my discussions with other patients with WM, I do not think that I am unique," he states.

"For many patients, symptoms progress slowly, from barely noticeable to increasingly severe," he writes — and even patients who have symptoms are often followed for years on a watch-and-wait basis without treatment.

Rather than considering some patients asymptomatic and others symptomatic, Leonard suggests clinicians consider using terms such as "WM not yet requiring treatment" or "WM requiring treatment," which would more accurately describe the patient's experience.

"If our terminology does not adequately acknowledge the symptoms that our patients experience, we are less likely to address those symptoms and the effects they have on a patient's quality of life," Leonard argues.

Leonard presented his arguments in a letter to the editor published online August 19 in the Journal of Clinical Oncology.

He was responding to a recently published study by researchers under lead author Mark Bustoros, MD, Dana-Farber Cancer Institute, Boston, Massachusetts. That study presented a model that allows clinicians to more accurately predict how long it will take for WM to progress, as as reflected in the patient's calculated risk category.

Authors' Response: We Agree

In a reply to Leonard's letter, the study authors agree with him. The term "asymptomatic" may not do justice to patients during the early stages of the disease process, when patients may experience symptoms while being followed with observation, they write. Among the more common early symptoms of WM are anemia, lymphadenopathy, and peripheral neuropathy.

"These symptoms may not be severe enough to warrant treatment initiation," Bustoros and colleagues write.

"However, they can affect a patient's quality of life," they concur. The point was underscored by Leonard's own experience as an "asymptomatic" WM patient.

"Perhaps the term 'WM under observation' would be a more accurate description of a patient's disease status without directly addressing the presence or absence of symptoms," the team suggests.

This term would have to be endorsed by other experts. "We agree that the potential presence of symptoms in patients with so-called 'asymptomatic' WM should be recorded and managed accordingly for improved quality of life," they acknowledge.

Progression of Disease

In their own study of 439 asymptomatic WM patients, Bustoros and colleagues found that for 72% of the cohort, disease progressed to symptomatic WM over a median follow-up period of 7.8 years.

They identified risk factors for disease progression that predicted how quickly patients would experience progression while they were still in an asymptomatic state.

A careful evaluation of these risk factors allowed researchers to categorize "asymptomatic" WM patients into three risk groups:

  • A high-risk group, for whom the median time to progression (TTP) was 1.8 years

  • An intermediate-risk group, for whom the median TTP was 4.8 years

  • A low–risk group, for whom the median TTP was 9.3 years

In their reply to Leonard, the authors suggest that patients in the high-risk asymptomatic subgroup could benefit from treatment or at the least be considered for clinical trials, regardless of the presence or absence of symptoms.

"Our study showed that patients who are wild-type for the MYD88 gene tend to experience faster disease progression," the team observes, "indicating that MYD88 wild-type disease is a potentially separate entity with more aggressive biology," they state.

Thus, the authors of the risk prediction model conclude that identifying patients who are at very low risk for progression — as well as those who will experience progression within a relatively short time after diagnosis — has "practice-changing" implications.

As such, "we encourage the use of our progression risk model and its accompanying calculator ( for an efficient, robust risk-stratification of patients with 'asymptomatic' WM," they conclude.

Leonard has disclosed no relevant financial relationships. Bustoros has received honoraria from Takeda and DAVA Oncology and has served as a consultant for Takeda. His coinvestigators report multiple ties with industry, which are listed in the original article.

J Clin Oncol. Published online April 16, 2019. Bustoros et al, Abstract

J Clin Oncol. Published online August 19, 2019. Leonard letter, Full text; Bustoros et al's reply, Full text

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