There is no single accepted treatment for<unk> . There is marked variation in clinical outcome due to gaps in knowledge of the disease's molecular basis. Objective response rates are high (> 80%) but complete response rates are low (0–15%). The medication ibrutinib targets the MYD88 L265P mutation induced activation of Bruton's tyrosine kinase. In a cohort study of previously treated patients, ibrutinib induced responses in 91% of patients, and at 2 years 69% of patients had no progression of disease and 95% were alive. Based on this study, the Food and Drug Administration approved ibrutinib for use in<unk>  in 2015. There are different treatment flowcharts: Treon and mSMART. Patients with<unk>  are at higher risk of developing second cancers than the general population, but it is not yet clear whether treatments are contributory. Watchful waiting In the absence of symptoms, many clinicians will recommend simply monitoring the patient;<unk>  himself stated "let well do" for such patients. These asymptomatic cases are now classified as two successively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance and smoldering<unk> . But on occasion, the disease can be fatal, as it was to the French president Georges Pompidou, who died in office in 1974. Mohammad Reza Shah Pahlavi, the Shah of Iran, also suffered from<unk> , which resulted in his ill-fated trip to the United States for therapy in 1979, leading to the Iran hostage crisis. First-line Should treatment be started it should address both the paraprotein level and the lymphocytic B-cells. In 2002, a panel at the International Workshop on<unk> 's<unk>  agreed on criteria for the initiation of therapy. They recommended starting therapy in patients with constitutional symptoms such as recurrent fever, night sweats, fatigue due to anemia, weight loss, progressive symptomatic lymphadenopathy or spleen enlargement, and anemia due to bone marrow infiltration. Complications such as hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, kidney failure, or symptomatic cryoglobulinemia were also suggested as indications for therapy. Treatment includes the monoclonal antibody rituximab, sometimes in combination with chemotherapeutic drugs such as chlorambucil, cyclophosphamide, or vincristine or with thalidomide. Corticosteroids, such as prednisone, may also be used in combination. Plasmapheresis can be used to treat the hyperviscosity syndrome by removing the paraprotein from the blood, although it does not address the underlying disease. Ibrutinib is another agent that has been approved for use in this condition. Combination treatment with Ibrutinib and Rituximab showed significantly higher disease progression free survival than with just Rituximab treatment. Autologous bone marrow transplantation is a treatment option. Zanubrutinib is indicated for the treatment of adults with<unk> . Salvage therapy When primary or secondary resistance invariably develops, salvage therapy is considered. Allogeneic stem cell transplantation can induce durable remissions for heavily pre-treated patients. Drug pipeline As of October 2010, there have been a total of 44 clinical trials on<unk> , excluding transplantation treatments. Of these, 11 were performed on previously untreated patients, 14 in patients with relapsed or refractory<unk> . A database of clinical trials investigating<unk>  is maintained by the National Institutes of Health in the US. Patient stratification Patients with polymorphic variants (alleles) FCGR3A-48 and -158 were associated with improved categorical responses to rituximab-based treatments.
Waldenström macroglobulinemia
Monoclonal gammopathy of undetermined significance
AL amyloidosis
Fibrin-associated diffuse large B-cell lymphoma
POEMS syndrome
Thymoma with immunodeficiency
Multiple myeloma
Diffuse large B-cell lymphoma