Diagnosis and Management of Waldenström Macroglobulinemia

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 harboring MYD88 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.

Waldenstrom’s Macroglobulinemia: An Update

“… 74 On the other hand, single-agent rituximab represents a valid option in the presence of immunologic disorders related to MW, such as symptomatic cryoglobulinemia, haemolytic anaemia or isolated IgM related peripheral neuropathy. 74 , 80 A recent publication demonstrated a significant clinical improvement in almost half of the patients with anti-MAG antibody neuropathy treated with Rituximab in monotherapy. 81 …”

Waldenström macroglobulinemia treatment algorithm 2018

“…Hyperviscosity is an uncommon manifestation of Waldenström macroglobulinemia. The most common presentation is nasal or gingival bleeding 36 . Because of the risk of retinal and central nervous system hemorrhage, emergency therapy is required in conjunction with immediate initiation of systemic chemotherapy.…”

Profiling of circulating exosomal miRNAs in patients with Waldenström Macroglobulinemia

“…Informed consent was obtained from all patients in accordance with the Declaration of Helsinki. The patients’ disease status was determined based on the Mayo stratification of Macroglobulinemia[ 2 ]. A total of 84 samples were analyzed including 10 healthy controls, 30 smoldering WM and 44 symptomatic WM.…”

“…There are distinct stages of disease progression for WM, starting from the precursor condition termed IgM monoclonal gammopathy of undetermined significance (IgM MGUS) that is defined by a bone marrow infiltration below10%. IgM MGUS has a rate of progression of 1.5–2% risk of progression to WM per year[ 2 ]. Patients with smoldering/asymptomatic WM display no major symptoms and are observed until their disease progresses to symptomatic WM[ 3 ].…”