Treatment Waldenström's macroglobulinemia

1 treatment

1.1 watchful waiting
1.2 first-line
1.3 salvage therapy
1.4 drug pipeline
1.5 patient stratification

treatment

there no single accepted treatment wm. there marked variation in clinical outcome due gaps in knowledge of disease s molecular basis. objective response rates high (> 80%) complete response rates low (0–15%). recently, yang et al. showed myd88 l265p mutation induced activation of bruton s tyrosine kinase, target of drug ibrutinib. among treated patients, ibrutinib induced responses in 91% of patients, , @ 2 years 69% of patients had no progression of disease , 95% alive (treon et al., new england journal of medicine 2015). based on study, food , drug administration approved ibrutinib use in wm in 2015.

there different treatment flowcharts: treon , msmart.

wm patients @ higher risk of developing second cancers general population, not yet clear whether treatments contributory.

watchful waiting

in absence of symptoms, many clinicians recommend monitoring patient; waldenström himself stated let such patients. these asymptomatic cases classified 2 successively more pre-malignant phases, igm monoclonal gammopathy of undetermined significance (i.e. igm mgus) , smoldering waldenström s macroglobulinemia.

but on occasion, disease can fatal, french president georges pompidou, died in office in 1974. mohammad reza shah pahlavi, shah of iran, suffered waldenström s macroglobulinemia, resulted in ill-fated trip united states therapy in 1979, leading iran hostage crisis.

first-line

should treatment started should address both paraprotein level , lymphocytic b-cells.

in 2002, panel @ international workshop on waldenström s macroglobulinemia agreed on criteria initiation of therapy. recommended starting therapy in patients constitutional symptoms such recurrent fever, night sweats, fatigue due anemia, weight loss, progressive symptomatic lymphadenopathy or spleen enlargement, , anemia due bone marrow infiltration. complications such hyperviscosity syndrome, symptomatic sensorimotor peripheral neuropathy, systemic amyloidosis, kidney failure, or symptomatic cryoglobulinemia suggested indications therapy.

treatment includes monoclonal antibody rituximab, in combination chemotherapeutic drugs such chlorambucil, cyclophosphamide, or vincristine or thalidomide. corticosteroids, such prednisone, may used in combination. plasmapheresis can used treat hyperviscosity syndrome removing paraprotein blood, although not address underlying disease. ibrutinib agent has been approved use in condition.

recently, autologous bone marrow transplantation has been added available treatment options.

salvage therapy

when primary or secondary resistance invariably develops, salvage therapy considered. allogeneic stem cell transplantation can induce durable remissions heavily pre-treated patients.

drug pipeline

as of october 2010, there have been total of 44 clinical trials on waldenström s macroglobulinemia, excluding transplantation treatments. of these, 11 performed on untreated patients, 14 in patients relapsed or refractory waldenström s. database of clinical trials investigating waldenström s macroglobulinemia maintained national institutes of health in us.

patient stratification

patients polymorphic variants (alleles) fcgr3a-48 , -158 associated improved categorical responses rituximab-based treatments.