Consensus updates on the management of symptomatic, previously treated WM patients
| Re-treatment | Treatment with any of the interventions listed for symptomatic, untreated patients can be considered for previously treated patients requiring therapy. Re-treatment may be considered with any of the above interventions if a response was achieved for 2 or more years with the prior regimen. Patients who progressed on first-line ibrutinib should not be retreated with ibrutinib. |
| Ofatumumab | In patients with intolerance to rituximab, ofatumumab is a potential therapeutic option. |
| Ibrutinib | Ibrutinib is an option in symptomatic WM patients. Ibrutinib is approved as primary therapy in WM patients by the US Food and Drug Administration, Health Canada, and the European Medicines Agency as primary therapy in WM patients who are not candidates for chemoimmunotherapy. Ibrutinib should not be stopped unless toxicity or disease progression is suspected. Increases in serum IgM and reductions in hemoglobin can occur if ibrutinib is held, and should not be regarded as treatment failure. The optimal use of ibrutinib (ie, as first-line treatment or in previously treated disease) as a single agent or in combination continues to be a subject of investigation. |
| Nucleoside analogs | Fludarabine-based combinations can be considered in fit WM patients with previously treated disease for whom other less toxic treatments have failed. In young patients who are eligible for autologous SCT (ASCT), stem cells should be collected before fludarabine administration. |
| Everolimus | Everolimus can be considered as a treatment option in the relapsed or refractory setting, although owing to the toxicities associated with this agent, everolimus is best considered in patients who are unresponsive or progressed after multiple lines of other better-tolerated therapies. Serial BM biopsies may help clarify underlying disease response or progression to everolimus, given the IgM discordance observed with this agent. |
| Immunomodulatory agents | On the basis of the current data, the use of lenalidomide and pomalidomide should be considered in the context of a clinical trial, given their potential adverse events. |
| Stem cell transplantation | The panel agrees that stem cell transplantation (SCT) should be discussed in selected WM cases, although physicians should take into account the numerous available alternative treatment options. ASCT is a feasible and effective treatment option for high-risk WM patients who are eligible for transplant, but should ideally be offered at early relapses. ASCT is not as beneficial for patients exposed to more than 3 lines of therapy or with chemotherapy refractory disease. Allogeneic SCT, when appropriate, should preferably be considered in the context of clinical trials. |
| Re-treatment | Treatment with any of the interventions listed for symptomatic, untreated patients can be considered for previously treated patients requiring therapy. Re-treatment may be considered with any of the above interventions if a response was achieved for 2 or more years with the prior regimen. Patients who progressed on first-line ibrutinib should not be retreated with ibrutinib. |
| Ofatumumab | In patients with intolerance to rituximab, ofatumumab is a potential therapeutic option. |
| Ibrutinib | Ibrutinib is an option in symptomatic WM patients. Ibrutinib is approved as primary therapy in WM patients by the US Food and Drug Administration, Health Canada, and the European Medicines Agency as primary therapy in WM patients who are not candidates for chemoimmunotherapy. Ibrutinib should not be stopped unless toxicity or disease progression is suspected. Increases in serum IgM and reductions in hemoglobin can occur if ibrutinib is held, and should not be regarded as treatment failure. The optimal use of ibrutinib (ie, as first-line treatment or in previously treated disease) as a single agent or in combination continues to be a subject of investigation. |
| Nucleoside analogs | Fludarabine-based combinations can be considered in fit WM patients with previously treated disease for whom other less toxic treatments have failed. In young patients who are eligible for autologous SCT (ASCT), stem cells should be collected before fludarabine administration. |
| Everolimus | Everolimus can be considered as a treatment option in the relapsed or refractory setting, although owing to the toxicities associated with this agent, everolimus is best considered in patients who are unresponsive or progressed after multiple lines of other better-tolerated therapies. Serial BM biopsies may help clarify underlying disease response or progression to everolimus, given the IgM discordance observed with this agent. |
| Immunomodulatory agents | On the basis of the current data, the use of lenalidomide and pomalidomide should be considered in the context of a clinical trial, given their potential adverse events. |
| Stem cell transplantation | The panel agrees that stem cell transplantation (SCT) should be discussed in selected WM cases, although physicians should take into account the numerous available alternative treatment options. ASCT is a feasible and effective treatment option for high-risk WM patients who are eligible for transplant, but should ideally be offered at early relapses. ASCT is not as beneficial for patients exposed to more than 3 lines of therapy or with chemotherapy refractory disease. Allogeneic SCT, when appropriate, should preferably be considered in the context of clinical trials. |