World Leukemia and Lymphoma Awareness Month

September 4th, World leukemia day, reminds us of the severity of leukemia.

September 15th, World Lymphoma Awareness Day, brings attention to the health of the lymphatic system.

September 22nd，World Chronic Myeloid Leukemia Day places special emphasis on the long-term management and treatment of this disease.

In April 2024, the WHO International Agency for Research on Cancer team published the 2022 global malignant tumor statistical report in CA: A Cancer Journal for Clinicians, which focused on the incidence and death of 36 malignant tumors in 185 countries or regions in the world and analyzed the differences between different sexes, geographical regions and different economic regions divided by the human development index. According to estimates, there were 481,777 new cases of leukemia and 305,033 deaths. ^[1]

Chronic Myeloid Leukemia (CML)

Leukemia is a malignant clonal disease of hematopoietic stem cells, which can be manifested as fever, anemia, lymph node swelling, fatigue, and hyperhidrosis in clinic. The growth disorder of leukemia cells leads to the stagnation of white blood cells in different stages of cell development, which accumulates in a large amount in bone marrow and other hematopoietic tissues, thus affecting normal hematopoiesis. It can be clinically divided into acute leukemia and chronic leukemia. More commonly in adults, CML is a malignant tumor formed by clonal proliferation of bone marrow hematopoietic stem cells and is characterized by the presence of a Ph chromosome and a BCR-ABL fusion gene. Gene detection is essential for the diagnosis of CML, and the detection of Ph chromosome and BCR-ABL fusion gene is one of the criteria for the diagnosis of CML.

In the treatment of CML, tyrosine kinase inhibitor (TKI) is a first-line therapeutic agent, including Imatinib, Nilotinib, Dasatinib, Panatinib and Olverembatinib. During the treatment, the efficacy was evaluated by monitoring the level of BCR-ABL fusion genes (such as p190 and p210), and whether there was T315I resistance mutation in BCR-ABL and the treatment protocol was adjusted in time. Deep molecular reactions (DMR) are an important goal of CML therapy. Some patients may achieve long-term treatment-free remission (TFR) through TKI therapy, that is, functional cure. ^[2]

Imatinib and three second-generation TKIs (Bosutinib, Dasatinib, and Nilotinib) were found to have comparable survival outcomes in the first-line treatment of chronic CML (CML-CP) in a multi-drug parallel-comparison clinical trial. The choice of second-generation TKI or Imatinib for first-line treatment depends on the treatment objective (survival, TFR), CML risk, drug costs, and toxicity profile associated with the patient's comorbidities. For patients with genuine second-generation TKIs resistance or a gate mutation in T315I, third-generation TKIs are preferred. As a result of the accumulated experience and results with subsets of CML, including the T315I mutant CML, consideration should first be given to propranolol. Response-based doses of Ponatinib were safe and resulted in high TKI adherence. Asciminib is a third-generation TKI that may have a better toxicity profile, but is less active in CML with the T315I mutation. Olverembatinib is another effective third-generation TKI with good results. The drug became effective on March 1, 2023, and the payment scope is limited to: "Adult patients with chronic myeloid leukemia (CML) CP or AP with T315I mutation. ^[3]

Lymphoplasmacytic lymphoma/Waldenström Macroglobulinemia（LPL/WM）

Lymphoma, also known as malignant lymphoma, is a general term of a group of malignant tumors originated from the lymphoid hematopoietic system, and is one of the common malignant tumors in China. Lymphoma (LYMPHOMA) is divided into Hodgkin's lymphoma (Hodgkin Lymphoma, HL) and non-Hodgkin's lymphoma (NHL), in which the incidence of NHL is about 10 times that of HL, and the mortality of NHL is 20 times that of HL.

LPL/WM is a rare inactive mature B-cell lymphoma that accounts for < 2% of non-Hodgkin's lymphomas. The MYD88 L265P mutation has a high detection rate (> 90%) in patients with Fahrenheit macroglobulinemia and can be used to differentiate and diagnose the disease; WM is diagnosed when LPL invades bone marrow and is accompanied by hemolistic clonal IgM gamma globulin, and WM accounts for 90%–95% of LPL. Furthermore, the use of this mutation can help to differentiate WM from marginal zone lymphoma with a diagnostic specificity and sensitivity of 98% and 87%, respectively. Studies have shown that the status of MYD88 L265P mutation is also a prognostic factor for WM. The prognosis of WM patients with MYD88 L265P mutation is significantly better than those without MYD88 L265P mutation. ^[4]

Based on ASPEN research, Zanubrutinib has been successfully granted WM treatment indications in the United States, Canada, China, Australia, the European Union and other countries, and has been recommended as a single drug for WM by the National Comprehensive Cancer (NCCN) Guidelines (2024 V2). Moreover, Zanubrutinib has obtained the 2023 mSMART Guidelines (Mayo Myeloma Stratification and Risk Adjustment Treatment) and the 2022 WM only recommended by the authoritative organization of NICE (National Institute for Health and Clinical Excellence), which have become an international standard. ^[5]

SpaceGen detection scheme

References

[1] CA Cancer J Clin. 2024 May-Jun; 74(3):229-263.

[2] NCCN Guidelines Version 2.2024 Chronic Myeloid Leukemia

[3] Blood Cancer J. 2023; 13(1):58.

[4] NCCN Guidelines Version 2.2024  Waldenström Macroglobulinemia/ Lymphoplasmacytic Lymphoma

[5] Blood 2020; 136:2038-50.