What are the regimens used in salvage therapy for Waldenstrom macroglobulinemia (WM)?

Updated: Aug 06, 2020
  • Author: Joseph M Tuscano, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Answer

Many of the regimens listed above that were not used as initial therapy can be considered as a salvage approach. In addition, many centers recommend retreating with the initial regimen if it was well tolerated and resulted in a durable remission (lasting > 3 years). Other salvage approaches include the following

  • Carfilzomib/rituximab/dexamethasone [20] : Induction: carfilzomib 20 mg/m 2 (cycle 1 only), then 36 mg/m 2 (for cycles 2 and beyond), with dexamethasone 20 mg on days 1, 2, 8, and 9 and rituximab 375 mg/m on days 2 and 9 every 21 days for six cycles. Maintenance: carfilzomib 36 mg/m 2 and dexamethasone 20 mg on days 1 and 2, rituximab 375 mg/m on day 2 every 8 weeks for eight cycles  
  • Thalidomide/rituximab [21] : Thalidomide 200 mg/day for 2 weeks, then 400 mg for 50 weeks; rituximab 375 mg/m 2 once weekly on weeks 2 to 5 and 13 to 16
  • Alemtuzumab [22] : 30 mg IV 3 times weekly for up to 12 weeks
  • Autologous SCT

In addition, therapies under investigation include ixazomib, ofatumumab, venetoclax, zanubrutinib, and pembrolizumab. [23, 24, 25]

Autologous SCT should be considered in patients with good functional status and adequate organ function who have multi-relapsed or refractory and chemosensitive disease. A multi-center study from the European Bone Marrow Transplant Registry demonstrated 5-year progression-free survival (PFS) and overall survival of 40% and 69%, respectively, for patients with predominantly multi-relapsed or refractory disease who had received autologous SCT. [26] One-year nonrelapse mortality was low at 4%; factors that impacted survival included number of previous lines of therapy and the presence of chemo-refractory disease.

When selecting initial and salvage therapies for patients who may eventually be considered for autologous SCT, exposure to stem cell–damaging agents such as alkylating agents and purine analogs should be avoided. Because many of the standard regimens do contain alkylating agents and purine analogs, many centers recommend either collecting stems cells early to be sequestered for a later transplant or not waiting later than the second or third chemosensitive salvage before considering autologous SCT. [27]

Allogeneic SCT has resulted in some very durable remissions, with the largest study reporting a 5-year PFS of 46% in heavily pretreated patients. [28] However, transplant-related mortality remains significant, with a 5-year nonrelapse mortality of 30%, so this approach should only be utilized in younger patients in whom standard treatment options have failed and optimally as part of a clinical trial. [29]


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