Professor Li Jian: Progress in Diagnosis and Treatment of Fahrenheit Macroglobulinemia|The First National Lymphocytic Disease Academic Conference of the Chinese Medical Association

On April 16-18, 2021, the First National Lymphocytic Disease Academic Conference of the Chinese Medical Association and the 2021 International Lymphoma Update Symposium were successfully held in Chengdu, Sichuan Province.

At the meeting, Professor Li Jian from Peking Union Medical College Hospital of the Chinese Academy of Medical Sciences introduced the diagnosis and treatment progress of Fahrenheit's macroglobulinemia (WM).
Yimaitong is now organized as follows for readers.

WM diagnosis method Professor Li Jian said that the core elements of WM diagnosis include 1) positive serum monoclonal IgM; 2) the presence of CD5-CD10-monoclonal B cells in the bone marrow; 3) the presence of WM-related clinical symptoms.

The clinical manifestations of WM are highly heterogeneous, among which anemia, B symptoms, and organ enlargement are the most common.

In addition, rare complications related to WM (such as light chain amyloidosis, cold agglutinin disease, cryoglobulinemia, etc.
) are also worthy of attention.

MYD88L265P is a driver mutation of WM.
Studies have shown that the mutation rate of MYD88L265P in WM is over 90%.

CXCR4WHIM is a minor mutation of WM, and its mutation rate is about 20%-30%.

Professor Li Jian said that the MYD88L265P mutation is more common in WM and can distinguish marginal zone lymphoma (MZL) from WM.
The overall sensitivity and specificity are more than 90%.

Professor Li Jian said that for the clinically suspected WM but MYD88 mutation is negative, possible reasons include false negative MYD88 mutation, not WM or MYD88 wild-type WM.

Later, Professor Li Jian emphasized that attention should be paid to the detection method and false negative rate of MYD88.
Different detection methods have different detection sensitivity.
When interpreting the results, it is necessary to pay attention to the detection method and eliminate the possibility of false negatives as much as possible.

In addition, the positive rate of bone marrow test is relatively high, but Professor Li Jian reminded us to pay attention to the possibility of false negatives caused by bone marrow dilution.

Peripheral blood test is generally negative, but peripheral blood cfDNA detection of MYD88L265P mutation has high sensitivity (89%) and specificity (89%).

In addition, the gene mutation spectrum of MYD88 wild-type and MYD88 mutant WM is different (the gene mutation spectrum of MYD88 wild-type is more similar to diffuse large B-cell lymphoma [DLBCL]), although the clinical and pathological features of the two are similar, but MYD88 wild-type WM progresses faster and the prognosis is worse.

WM treatment options Professor Li Jian emphasized that IgM level alone is not an indication for initiating WM treatment.
Symptoms/complications are important indications for initiation of WM treatment, including B symptoms, obvious fatigue, anemia/thrombocytopenia, and hyperviscosity.
Syndrome, amyloidosis/other sedimentary diseases, cold agglutinin disease, etc.

There are many treatment options for WM, including rituximab (R) combined regimen: BR regimen (rituximab, bendamustine), DRC regimen (rituximab, cyclophosphamide, dexamethasone) Methsone), FCR regimen (rituximab, cyclophosphamide, fludarabine), BRD regimen (rituximab, bortezomib, dexamethasone), etc.
and BTK inhibitors.

The curative effect of the treatment plan based on the fixed cycle of rituximab and the single-agent effect of BTK inhibitor (Ibrutinib) are both good, as shown in the figure below.

In addition, Ibrutinib is effective in treating patients with MYD88 mutant and CXCR4 wild-type WM.
The overall response rate (ORR) can reach 100%, and the main response rate can reach 97%.

Comparison of the efficacy of treatment programs based on rituximab on a fixed cycle.
The efficacy of ibrutinib as a single agent of 420 mg qd in the treatment of WM.
Professor Li Jian emphasized that at present, there is "no best, only more suitable" treatment option for WM, which requires individualized treatment .

For the elderly/patients with poor physical status, BTK inhibitors can be selected; for younger/better patients with physical status, BR can be selected; for patients with strong treatment urgency, BR/RBD can be selected; for patients with weak treatment urgency, you can choose BTK inhibitor/DRC regimen.

Subsequently, Professor Li Jian introduced the hypoarrest syndrome of BTK inhibitors: BTK inhibitors inhibit cytokines such as TNFα/CXCL13 and the function of T/macrophages, and hypoarrest syndrome is prone to occur after reduced arrest, with an incidence of about 20%.
, The appearance time is the median 2 days (0-5 days) after reduction and stop, and sufficient attention should be paid.

The main manifestations of reduced arrest syndrome are fever, body aches, night sweats, joint pain, chills, headaches, fatigue, etc.
, which are often accompanied by elevated IgM.
We should also be alert to the occurrence of IgM-related hyperviscosity/cryoglobulin aggravation.

Symptoms can be quickly relieved after the BTK inhibitor is given again, or prednisone 10mg Bid is given.

Finally, Professor Li Jian concluded that the MYD88 mutation is of great value in the diagnosis of WM, and the CXCR4 mutation can guide treatment options.

In terms of treatment, it is more important to make individualized treatment options based on the patient's individual situation.

Professor Li Jian, Chief Physician and Doctoral Supervisor, Deputy Director of the Department of Hematology, Peking Union Medical College Hospital, Member of the Hematology Branch of the Chinese Medical Association Member of the Multiple Myeloma Professional Committee of the Chinese Medical Doctor Association Member of the Hematological Oncology Committee of the Chinese Anti-Cancer Association Member of the Editorial Board of the Chinese Journal of Hematology "Read the original", we make progress together