What are the treatment guidelines for Waldenstrom macroglobulinemia (WM)?

Updated: Feb 01, 2021
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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NCCN guidelines recommend treatment of WM only in patients with the following symptoms [55] :

  • Hyperviscosity
  • Neuropathy
  • Organomegaly
  • Amyloidosis
  • Cold agglutinin disease
  • Cryoglobulinemia
  • Anemia and other cytopenias associated with WM
  • Bulky adenopathy

High monoclonal IgM level alone generally does not justify treatment initiation in the absence of other symptoms. [56, 55]  

ESMO guidelines similarly recommend treatment in patients with constitutional symptoms, cytopenias, hyperviscosity, moderate or severe neuropathy, amyloidosis, symptomatic cryoglobulinemias, and/or cold agglutinin disease. Asymptomatic WM should be managed with watchful waiting, with monitoring every 3-6 months. [56]

Both guidelines recommend treating hyperviscosity syndrome with plasmapheresis for immediate relief, followed by appropriate systemic therapy. [56, 55]

For the primary treatment of WM, the NCCN and the IWWM-10 recommend the following as preferred regimens (listed aphabetically) [55, 31] :

  • Bendamustine plus rituximab
  • Bortezomib, dexamethasone, and rituximab
  • Cyclophosphamide, dexamethasone, and rituximab
  • Ibrutinib with or without rituximab (NCCN category 1 recommendation)

The IWWM-10 also lists the following as treatment options [31] :

  • Acalabrutinib
  • Carfilzomib, dexamethasone, and rituximab
  • Fludarabine and rituximab
  • Ixazomib, dexamethasone, and rituximab
  • R-CHOP (rituximab, cyclophosphamide, doxorubicin [hydroxydaunorubicin], vincristine [Oncovin], and prednisone)
  • R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone)
  • Rituximab
  • Ofatumumab

Additional IWWM-10 treatment recommendations are as follows [31] :

  • Avoid bortezomib and vincristine in patients with neuropathy
  • Avoid carfilzomib in patients with cardiac disease and those older than 65 years
  • Avoid nucleoside analogues (ie, fludarabine, cladribine) in patients who are candidates for stem-cell transplantation
  • Consider delaying rituximab if serum IgM concentrations are greater than 4000 mg/dL, due to risk of IgM flare
  • Consider ofatumumab in patients who are intolerant to rituximab

ESMO-recommended primary treatment options include rituximab plus alkylating agents (oral or IV cyclophosphamide or bendamustine) or proteasome inhibitors. Monotherapy with alkylating agents, nucleoside analogues, or rituximab should be considered only in patients who are not candidates for more effective chemoimmunotherapy combinations. [56]

ESMO guidelines do not recommend rituximab maintenance therapy; [56] The NCCN recommends considering rituximab for maintenance in patients who have achieved a complete, very good, partial, or minor response to induction therapy. [55]  

For relapsed disease, NCCN recommends repeating the regimen used for primary treatment, especially if it was well tolerated and the patient had a prolonged response. For relapse that occurs after less than 24 months, or progressive disease, the patient may be treated with a different class of drugs, either alone or in combination. Ofatumumab may be used for rituximab-intolerant patients. [55]

According to ESMO guidelines, the treatment of choice for WM relapse within 12 months of chemoimmunotherapy, including rituximab-refractory disease, is ibrutinib monotherapy. Ibrutinib monotherapy may be considered in patients who are ineligible for chemoimmunotherapy as first-line therapy. In patients with late WM relapses after chemoimmunotherapy, regimens to consider include an alternative chemoimmunotherapy combination, a prior effective regimen, or ibrutinib. [56]

Autologous stem cell transplantation (ASCT) may be appropriate in select patients. [56, 55]

All patients with WM should be strongly encouraged to enroll in clinical trials.

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