Select Topic:
Browse by Series:

Approaching Newly Diagnosed Waldenstrom Macroglobulinemia

Insights From: Meletios A. Dimopoulos, MD, the National and Kapodistrian University of Athens School of Medicine; Steven P. Treon, MD, PhD, Dana-Farber Cancer Institute
Published: Friday, Mar 29, 2019



Transcript: 

Meletios A. Dimopoulos, MD:
Waldenström macroglobulinemia, by definition, is not a localized disease. It’s a systemic disease. Several years ago, the International Staging System [ISS] for Waldenström macroglobulinemia was developed in order to provide a prognostic system so that we could understand the severity of the disease. It is based on readily available parameters such as hemoglobin, beta 2-microglobulin, the age of the patient, and the level of the monoclonal protein. The patient is classified as having a low, intermediate, or high ISS stage. There is a correlation of survival with the ISS stage of the patient.

Much more common than symptomatic Waldenström macroglobulinemia is the so-called IgM monoclonal protein of undetermined significance. We know that overall, if we perform a serum protein electrophoresis in normal individuals older than 50 years of age, in approximately 5% of those we will detect a monoclonal protein. The most frequent monoclonal protein would be IgG, and then IgA, and then third would be IgM. So this is not a disease; it is a condition. Whenever we detect an IgM monoclonal protein, we will do a work-up to make sure that there is no bone marrow infiltration or there is minimal bone marrow infiltration.

On the other hand, asymptomatic or smoldering Waldenström macroglobulinemia is a condition detected by chance without any symptoms and signs attributed to the underlying Waldenström. In this particular case, we usually have more than 10% infiltration by lymphoplasmacytic cells in the bone marrow and/or more than 3 grams of monoclonal protein. This condition needs closer follow-up than the IgM MGUS [monoclonal gammopathy of undetermined significance] because these patients are at high risk to progress to symptomatic Waldenström macroglobulinemia.

Within patients with IgM MGUS and the asymptomatic or smoldering Waldenström macroglobulinemia, patients with a higher level of monoclonal protein and more infiltration with lymphoplasmacytic cells are more likely to progress to symptomatic disease. But all patients need to be followed up on, in order to detect progression early.

Steven P. Treon, MD, PhD: It’s important to keep in mind that the NCCN [National Comprehensive Cancer Network] guidelines are meant to give a clinician options that are available for the treatment of their patient based on best available evidence. We know that many different options are included there. The NCCN guidelines help you understand what particular patients would perhaps benefit by a specific treatment approach. When one refers to the NCCN guidelines, one should really keep in mind whether the patient needs to be treated, because there are a fair number of patients who should be watched and waited on. It should also give you a sense of how to treat with specific morbidities, regarding what treatment options one should consider using, and you should keep both short-term and long-term consequences of therapy in mind.

I think this is really important because as we look at a patient, a young patient is going to need a different treatment approach perhaps than an older patient. And what’s considered an older patient these days has changed. Younger means anybody younger than the oncologist, and as the oncologists are getting older I think it means that most people out there who need therapy are younger. But I think in spirit that’s true. We ought to really be looking at the long-term impact of any type of therapy that we’re using these days, because our past experiences have been that the use of many of the drugs that we used to rely on, particularly nucleoside analogs, just led to more problems down the line. So it’s nice to see that the NCCN guidelines are expanded these days. They take into account short-term and long-term liabilities, but they also take into account the specifics of a patient.

Meletios A. Dimopoulos, MD: The NCCN guidelines, as we know, are usually very comprehensive and include all possible therapies that a physician could prescribe for a patient so that this treatment is reimbursed. At the time of relapse of a patient with Waldenström macroglobulinemia, it is important to know what the first-line treatment was and whether the patient relapsed off therapy or on treatment. And depending on the primary therapy, then the physician has several options to administer at the time of relapse. For example, 1 common regimen for the frontline treatment of patients with this disease is the combination of cyclophosphamide, dexamethasone, and rituximab or bendamustine and rituximab. These regimens are usually associated with a relatively long progression-free survival, and many patients relapse off therapy. At the time of relapse, again, rituximab-based therapy may be used, or in some patients, a BTK [Bruton tyrosine kinase] inhibitor such as ibrutinib may be indicated. There are pros and cons with these treatments for patients with this disease.


Transcript Edited for Clarity 
Slider Left
Slider Right


Transcript: 

Meletios A. Dimopoulos, MD:
Waldenström macroglobulinemia, by definition, is not a localized disease. It’s a systemic disease. Several years ago, the International Staging System [ISS] for Waldenström macroglobulinemia was developed in order to provide a prognostic system so that we could understand the severity of the disease. It is based on readily available parameters such as hemoglobin, beta 2-microglobulin, the age of the patient, and the level of the monoclonal protein. The patient is classified as having a low, intermediate, or high ISS stage. There is a correlation of survival with the ISS stage of the patient.

Much more common than symptomatic Waldenström macroglobulinemia is the so-called IgM monoclonal protein of undetermined significance. We know that overall, if we perform a serum protein electrophoresis in normal individuals older than 50 years of age, in approximately 5% of those we will detect a monoclonal protein. The most frequent monoclonal protein would be IgG, and then IgA, and then third would be IgM. So this is not a disease; it is a condition. Whenever we detect an IgM monoclonal protein, we will do a work-up to make sure that there is no bone marrow infiltration or there is minimal bone marrow infiltration.

On the other hand, asymptomatic or smoldering Waldenström macroglobulinemia is a condition detected by chance without any symptoms and signs attributed to the underlying Waldenström. In this particular case, we usually have more than 10% infiltration by lymphoplasmacytic cells in the bone marrow and/or more than 3 grams of monoclonal protein. This condition needs closer follow-up than the IgM MGUS [monoclonal gammopathy of undetermined significance] because these patients are at high risk to progress to symptomatic Waldenström macroglobulinemia.

Within patients with IgM MGUS and the asymptomatic or smoldering Waldenström macroglobulinemia, patients with a higher level of monoclonal protein and more infiltration with lymphoplasmacytic cells are more likely to progress to symptomatic disease. But all patients need to be followed up on, in order to detect progression early.

Steven P. Treon, MD, PhD: It’s important to keep in mind that the NCCN [National Comprehensive Cancer Network] guidelines are meant to give a clinician options that are available for the treatment of their patient based on best available evidence. We know that many different options are included there. The NCCN guidelines help you understand what particular patients would perhaps benefit by a specific treatment approach. When one refers to the NCCN guidelines, one should really keep in mind whether the patient needs to be treated, because there are a fair number of patients who should be watched and waited on. It should also give you a sense of how to treat with specific morbidities, regarding what treatment options one should consider using, and you should keep both short-term and long-term consequences of therapy in mind.

I think this is really important because as we look at a patient, a young patient is going to need a different treatment approach perhaps than an older patient. And what’s considered an older patient these days has changed. Younger means anybody younger than the oncologist, and as the oncologists are getting older I think it means that most people out there who need therapy are younger. But I think in spirit that’s true. We ought to really be looking at the long-term impact of any type of therapy that we’re using these days, because our past experiences have been that the use of many of the drugs that we used to rely on, particularly nucleoside analogs, just led to more problems down the line. So it’s nice to see that the NCCN guidelines are expanded these days. They take into account short-term and long-term liabilities, but they also take into account the specifics of a patient.

Meletios A. Dimopoulos, MD: The NCCN guidelines, as we know, are usually very comprehensive and include all possible therapies that a physician could prescribe for a patient so that this treatment is reimbursed. At the time of relapse of a patient with Waldenström macroglobulinemia, it is important to know what the first-line treatment was and whether the patient relapsed off therapy or on treatment. And depending on the primary therapy, then the physician has several options to administer at the time of relapse. For example, 1 common regimen for the frontline treatment of patients with this disease is the combination of cyclophosphamide, dexamethasone, and rituximab or bendamustine and rituximab. These regimens are usually associated with a relatively long progression-free survival, and many patients relapse off therapy. At the time of relapse, again, rituximab-based therapy may be used, or in some patients, a BTK [Bruton tyrosine kinase] inhibitor such as ibrutinib may be indicated. There are pros and cons with these treatments for patients with this disease.


Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 14th Annual International Symposium on Melanoma and Other Cutaneous Malignancies®Apr 30, 20192.0
Oncology Consultations®: The Advancing Role of CAR T-Cell Therapies in Hematologic MalignanciesApr 30, 20191.5
Publication Bottom Border
Border Publication
x