Diagnosis and Management of Waldenström Macroglobulinemia
- 1 September 2017
- journal article
- practice guideline
- Published by American Medical Association (AMA) in JAMA Oncology
- Vol. 3 (9), 1257-1265
- https://doi.org/10.1001/jamaoncol.2016.5763
Abstract
Importance Waldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system. Observations Waldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course. The major classes of effective agents in WM include monoclonal antibodies, alkylating agents, purine analogs, proteasome inhibitors, immunomodulatory drugs, and mammalian target of rapamycin inhibitors. However, the highest-quality evidence from rigorously conducted randomized clinical trials remains scant. Conclusions and Relevance Recognizing the paucity of data, we advocate participation in clinical trials, if available, at every stage of WM. Specific indications exist for initiation of therapy. Outside clinical trials, based on the synthesis of available evidence, we recommend bendamustine-rituximab as primary therapy for bulky disease, profound hematologic compromise, or constitutional symptoms attributable to WM. Dexamethasone-rituximab-cyclophosphamide is an alternative, particularly for nonbulky WM. Routine rituximab maintenance should be avoided. Plasma exchange should be promptly initiated before cytoreduction for hyperviscosity-related symptoms. Stem cell harvest for future use may be considered in first remission for patients 70 years or younger who are potential candidates for autologous stem cell transplantation. At relapse, retreatment with the original therapy is reasonable in patients with prior durable responses (time to next therapy ≥3 years) and good tolerability to previous regimen. Ibrutinib is efficacious in patients with relapsed or refractory disease harboringMYD88 L265P mutation. In the absence of neuropathy, a bortezomib-rituximab–based option is reasonable for relapsed or refractory disease. In select patients with chemosensitive disease, autologous stem cell transplantation should be considered at first or second relapse. Everolimus and purine analogs are suitable options for refractory or multiply relapsed WM. Our recommendations are periodically updated as new, clinically relevant information emerges.This publication has 49 references indexed in Scilit:
- Progression in smoldering Waldenström macroglobulinemia: long-term resultsBlood, 2012
- Temporal and geographic variations of Waldenstrom macroglobulinemia incidenceCancer, 2011
- Rituximab and Subcutaneous 2-Chloro-2′-Deoxyadenosine as Therapy in Untreated and Relapsed Waldenström's MacroglobulinemiaClinical Lymphoma Myeloma and Leukemia, 2011
- Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) GuidelinesMayo Clinic Proceedings, 2010
- Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180Journal of Clinical Oncology, 2009
- The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemiaBlood, 2007
- Initial immunoglobulin M ‘flare’ after rituximab therapy in patients diagnosed with Waldenstrom macroglobulinemiaCancer, 2004
- Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: Consensus Panel Recommendations from the Second International Workshop on Waldenstrom's MacroglobulinemiaSeminars in Oncology, 2003
- Waldenström macroglobulinaemia: presenting features and outcome in a series with 217 casesBritish Journal of Haematology, 2001
- Incipient myelomatosis or «essential« hyperglobulinemia with fibrinogenopenia — a new syndrome?Acta Medica Scandinavica, 1944