Guide to the primary therapy of WM. HV, hyperviscosity; CRYO, cryoglobulinemia; CAGG, cold agglutinemia; BDR, bortezomib, dexamethasone, rituximab; Benda-R, bendamustine, rituximab; CaRD, carfilzomib, rituximab, dexamethasone; CDR, cyclophosphamide, dexamethasone, rituximab; FR, fludarabine, rituximab; IB, ibrutinib; R, rituximab. 1Consider blood warmers with plasmapheresis in patients with cryoglobulinemia or cold agglutinemia to avoid cryoprecipitation or agglutination. 2Can be considered in patients who are not wild type for MYD8869 and for those patients without bulky adenopathy or Bing-Neel syndrome. 3For patients requiring immediate disease control, consider twice weekly dosed bortezomib for 1 to 2 cycles, and then if the patient is stable, switch to weekly bortezomib to reduce risk of treatment related peripheral neuropathy. In patients not requiring immediate disease control, the use of weekly dosed bortezomib is preferable. Bortezomib should be avoided in patients with disease-related neuropathy. Bortezomib should be held for grade ≥2 treatment-related neuropathy. Acyclovir and famotidine (or equivalent) are strongly recommended for patients on proteasome inhibitor therapy. 4Rituximab should be held in patients with symptomatic HV, severe CRYO or CAGG, and in asymptomatic patients with serum IgM >4000 mg/dL to avoid an IgM flare and potentiation of symptoms. Ofatumumab may be considered for rituximab-intolerant patients. Consider maintenance rituximab for patients responding to a rituximab-containing regimen. See text for suggested dosing, cycles, and scheduling of therapy. A clinical trial should be considered whenever possible.
