Pleural Effusion in Waldenström Macroglobulinemia
Pleural effusion in WM is a rare but significant complication that indicates symptomatic disease requiring immediate initiation of systemic therapy, as it represents either direct tumor infiltration of the pleura, lymphatic obstruction from bulky adenopathy, or rarely chylothorax from thoracic duct involvement. 1
Clinical Significance and Diagnostic Implications
Pleural effusion in WM patients is uncommon but carries important prognostic and therapeutic implications:
Pleural effusion, particularly bilateral bloody pleural effusion, represents symptomatic organomegaly or organ infiltration, which is an absolute indication for treatment initiation according to IWWM consensus criteria. 1 This is not a "watch and wait" scenario—these patients require immediate therapy.
The presence of pleural effusion in WM can result from multiple mechanisms: direct tumor invasion of the pleura, lymphatic obstruction from bulky lymphadenopathy, rupture of thoracic duct branches causing chylothorax, or concurrent infection. 2, 3 Each mechanism requires different management considerations.
Bilateral bloody pleural effusion specifically suggests direct pleural involvement by lymphoplasmacytic cells or significant vascular compromise from tumor burden. 2, 3 This presentation is particularly rare and warrants aggressive diagnostic workup and treatment.
Immediate Management Approach
When pleural effusion is identified in a WM patient, the following algorithmic approach should be followed:
Acute Stabilization
Therapeutic thoracentesis should be performed immediately for symptomatic patients with dyspnea or chest tightness to provide rapid relief while diagnostic workup proceeds. 2, 3 This is both diagnostic and therapeutic.
Pleural fluid analysis must include: cell count with differential, cytology for lymphoplasmacytic cells, flow cytometry if cellular, protein/LDH for Light's criteria, triglycerides if chylothorax suspected, and cultures to exclude infection. 2, 3
Systemic Therapy Initiation
Bendamustine-rituximab is the preferred first-line regimen for WM patients presenting with pleural effusion, as this represents bulky/symptomatic disease requiring rapid disease control. 1 The Mayo Clinic MSMART guidelines specifically recommend BR for bulky disease and profound symptoms. 1
Alternative first-line option is dexamethasone-rituximab-cyclophosphamide (DRC), particularly if bendamustine is unavailable or contraindicated. 1 This regimen provides rapid disease control with acceptable toxicity.
Zanubrutinib or ibrutinib can be considered as first-line therapy in MYD88 L265P-mutated patients, though chemoimmunotherapy may provide more rapid cytoreduction for symptomatic pleural disease. 4 BTK inhibitors are highly effective but may take longer to achieve maximal response.
Treatment Monitoring and Expected Outcomes
Clinical response should be assessed by resolution of dyspnea, repeat thoracic imaging (ultrasound or CT) after 2-4 cycles of therapy, and serial IgM measurements. 2 Complete resolution of pleural effusion is achievable with appropriate systemic therapy.
The case series demonstrate complete resolution of bilateral pleural effusions after 4 cycles of bendamustine-rituximab, with concurrent hematologic recovery. 2 This establishes realistic treatment expectations.
Critical Pitfalls to Avoid
Do not attribute pleural effusion in WM to "heart failure" or other causes without thorough evaluation—this represents active disease requiring systemic therapy, not just symptomatic management. 2, 3 Missing the WM diagnosis delays appropriate treatment.
Do not use rituximab monotherapy in patients with pleural effusion and high IgM levels (>4000 mg/dL) without prophylactic plasmapheresis, as IgM flare could worsen hyperviscosity. 1 Combination regimens are superior to rituximab alone in this setting.
Do not delay systemic therapy while pursuing repeated thoracentesis—pleural effusion will recur without treating the underlying lymphoproliferative disorder. 2, 3 Drainage is temporizing; chemoimmunotherapy is curative.
Avoid fludarabine-based regimens as first-line therapy in patients with pleural effusion, as these are no longer recommended for primary therapy and are reserved for relapsed/refractory disease. 1 Bendamustine-rituximab or DRC are superior choices.