What is the best treatment approach for a patient with Waldenström macroglobulinemia (WM) presenting with chest tightness and tachycardia?

Treatment Approach for Waldenström Macroglobulinemia with Chest Tightness and Tachycardia

For a patient with Waldenström macroglobulinemia presenting with chest tightness and tachycardia, immediate plasmapheresis should be performed to address hyperviscosity syndrome, followed by a proteasome inhibitor-based therapy such as bortezomib-rituximab-dexamethasone (BDR). 1

Initial Management of Hyperviscosity

The patient's presentation with chest tightness and tachycardia strongly suggests hyperviscosity syndrome, a potentially life-threatening complication of Waldenström macroglobulinemia (WM) that requires immediate intervention:

1. Immediate plasmapheresis:

   • Must be performed without delay for symptomatic hyperviscosity 1
   • A 3-4 liter plasma exchange can lower IgM levels by 60-75% and reduce viscosity by at least 50% 1
   • Multiple exchanges may be necessary depending on symptom resolution 1

2. Laboratory assessment:

   • Check IgM levels, complete blood count, serum viscosity
   • Evaluate for other cardiac causes of symptoms

Systemic Therapy Selection

After addressing the acute hyperviscosity with plasmapheresis, systemic therapy must be initiated promptly:

First-line options (in order of preference for this presentation):

1. Proteasome inhibitor-based therapy (preferred for hyperviscosity):

   • Bortezomib-rituximab-dexamethasone (BDR) is recommended for patients with high IgM levels, symptomatic hyperviscosity, and those requiring urgent IgM reduction 1
   • Bortezomib can be started at twice-weekly dosing for 1-2 cycles to achieve rapid cytoreduction, then switched to weekly dosing to reduce neurotoxicity risk 1
   • Consider subcutaneous administration to further reduce neuropathy risk 1

2. Bendamustine-rituximab (BR):

   • Effective alternative with high response rates 1, 2
   • May not reduce IgM levels as rapidly as bortezomib-based regimens 1

3. Ibrutinib:

   • Option for patients who cannot tolerate chemotherapy 1, 2, 3
   • Note: Ibrutinib can cause cardiac side effects including atrial fibrillation, which may be concerning given the patient's tachycardia 3

Monitoring and Follow-up

1. During plasmapheresis:

   • Monitor vital signs, cardiac rhythm, and symptoms
   • Assess for resolution of chest tightness and tachycardia

2. During systemic therapy:

   • Regular monitoring of IgM levels, complete blood count, and viscosity
   • Cardiac monitoring, especially if ibrutinib is chosen
   • Neurological assessment for bortezomib-related neuropathy

3. Response assessment:

   • Evaluate response after 2-3 cycles of therapy
   • Consider treatment modification if inadequate response

Important Considerations and Pitfalls

• Rituximab flare: Rituximab can cause a temporary increase in IgM levels (flare) that may worsen hyperviscosity. Consider delaying rituximab until IgM levels are better controlled or use prophylactic plasmapheresis before rituximab in patients with high IgM levels (>4000 mg/dL) 1

• Cardiac evaluation: Given the presentation with chest tightness and tachycardia, a cardiac evaluation should be performed to rule out other cardiac conditions or WM-related cardiac involvement

• Neuropathy monitoring: Closely monitor for peripheral neuropathy with bortezomib-based regimens, as this is a common side effect and may require dose modification 1

• Treatment duration: Continue treatment until best response plus 2 additional cycles, or until toxicity necessitates discontinuation 1

The combination of immediate plasmapheresis followed by bortezomib-based therapy represents the most effective approach to rapidly control hyperviscosity symptoms while addressing the underlying disease in this patient with WM presenting with chest tightness and tachycardia.