It is incredible that DNA modifications in our genome cancorrelate with clinical presentation of an illness and can also be helpful to choose the best treatment against the illness. This is the case of Waldenstöm macroglobulinemia, as Jorge J. Castillo and Steven P. Treon explained in their review article published in 2020. (1)
The authors showed simultaneously with a classical clinical description the story of a real patient, who discovered his complicated situation only by alterations in his laboratory exams: a high protein level in blood, without physical symptoms.
How to confirm the diagnosis
Given an elevation of protein level in blood it is important to be referred to a hematologist/oncologist for more deepened exams. Firstly blood tests, as the antibody levels in the blood: an augmentation of a specific antibody, called IgM, can let you suspect an illness called Waldenström macroglobulinemia (WM). However, to confirm this diagnosis you also need a bone marrow biopsy. This biopsy is useful to show you the appearance of the bone marrow, that in case of WM is invaded by lymphoplasmacytoid cells. But it is necessary to study the DNA of these cells, in order to identify the presence of two mutations in some genes that compose your DNA: these are the so called MYD88 L265P mutation and CXCR4 mutation.
Other important investigations after the diagnosis
Once the diagnosis is established, you need further investigations in order to define the illness and its consequences better. The Computed tomography (CT) is very important to see in chest, abdomen, and pelvis if some lymph nodes or alternatively the spleen or the liver are involved by the cells that characterised the WM. A characteristic of this disease is also that the blood acquires a viscous consistence. This situation, called hyperviscosity, can generate problems in the eyes. Although this is not obligatory, it could happen: so an ophthalmologic control with funduscopic examination is required after the hematologist has established the diagnosis. These exams should be repeated yearly to control if vision problems appear.
To treat or not to treat?
Not all patients with WM should be treated, but only some patients. For example a patient with anemia that produces physical symptoms, as chronic fatigue. Or patients who involved lymph nodes in the body, e.g. in the chest or in the abdomen. Or patients with really viscous blood.
Drugs used for the first treatment
A careful and accuratediscussion between doctors and patients should take place on the positive and negative aspects of each treatment option. It is so important to define a personalised therapy, taking into account patient‘s specific symptoms and other diseases(diabetes…), DNA exams previously accomplished and, last but not least, side effects of the different drugs and the personal preference of the patients. A drug used for the first treatment of a WM could be Rituximab, but it is less effective in patients with very elevated levels of IgM in the blood. To solve that, other drugs could be combined with Rituximab, for example Ibrutinib.
When MW come back
Despite good results of a therapy, there is always the risk that the WM could appear again. In this context it is important to choose a drug on the basis of the clinical story of each patient. An interesting and promising option is represented by Ibrutinib. In the USA this drug has been approved for the treatment of patients with symptomatic WM in April of 2015, because in other studies Ibrutinib has given important advantages in terms of clinical response and patients survival without illness progression. (2)
However, Ibrutinib has effects on platelet aggregation in the blood, increasing the risk of bleeding with surgical procedures. Therefore, this drug can increase the risk of arrhythmia, especially atrial fibrillation. So a patient that takes Ibrutinib should be under the care of a cardiologist with experience with this complication. (3) It is important to say that about 20% of WM patients who discontinue ibrutinib temporarily might experience the so called withdrawal symptoms, like fever, night sweats, and fatigue. These symptoms could be fortunately be managed with low doses of steroids.
Future treatment options
Other drugs can be used to treat a WM and new treatment options have appeared in recent years. The choice is based increasingly on the knowledge of typical DNA alterations of the disease and many new drugs aim to apport more favourable and durable clinical responses (remission) and lower toxicity rates.
(2) Treon SP, Meid K, Gustine J, et al. Ibrutinib monotherapy produces longterm disease control in previously treated Waldenstrom’s macroglobulinemia. Final report of the PIVOTAL Trial (NCT01614821). Hematol Oncol. 2019;37(S2):184-185.
(3) Ganatra S, Sharma A, Shah S, et al. Ibrutinib-associated atrial fibrillation. JACC Clin Electrophysiol. 2018;4(12):1491-1500.