What is the appropriate treatment for a condition referred to as Bandiplus?

Treatment of Waldenström Macroglobulinemia (Bandiplus)

Rituximab-based regimens are the preferred treatment for Waldenström Macroglobulinemia (Bandiplus), with Bendamustine-Rituximab being the most effective option for most patients requiring therapy. 1

Disease Overview

Waldenström Macroglobulinemia (WM), also known as Bandiplus in some regions, is a rare B-cell lymphoproliferative disorder characterized by:

• Bone marrow infiltration by lymphoplasmacytic cells
• Production of monoclonal IgM paraprotein
• Potential for hyperviscosity syndrome and other IgM-related complications

Treatment Indications

Treatment should be initiated only for symptomatic patients. Asymptomatic patients should undergo a watch-and-wait strategy 1.

Indications for treatment include:

• Symptomatic hyperviscosity
• Cytopenias (hemoglobin <10 g/dL, platelets <100,000/μL)
• Constitutional symptoms (fever, night sweats, weight loss)
• Symptomatic lymphadenopathy or organomegaly
• Peripheral neuropathy related to WM
• Amyloidosis, cryoglobulinemia, or cold agglutinin disease

First-Line Treatment Options

Preferred Regimens:

1. Bendamustine-Rituximab (BR)

   • Most effective for patients who can tolerate chemotherapy
   • Well-tolerated even in elderly patients
   • Consider dose reduction in elderly or those with renal impairment
   • Four cycles may be sufficient for adequate response 1
   • Consider antibacterial/antiviral prophylaxis due to risk of infections 1

2. Rituximab-Cyclophosphamide-Dexamethasone (RCD)

   • Active and safe with manageable toxicity
   • Good option for frail patients requiring combination therapy 1

3. Bortezomib-based regimens

   • Recommended for patients with:
     • High IgM levels
     • Symptomatic hyperviscosity
     • Cryoglobulinemia or cold agglutinemia
     • Amyloidosis
     • Renal impairment
   • Should be given once weekly and preferably subcutaneously to reduce neurotoxicity 1

4. Ibrutinib

   • Option for symptomatic patients not candidates for chemoimmunotherapy
   • FDA-approved for primary therapy in WM 1
   • Note: IgM levels may transiently increase if ibrutinib is stopped 1

For Frail Patients:

• Rituximab monotherapy
  • Consider for patients with immunologic disorders related to WM
  • Avoid in patients with high IgM levels (>4000 mg/dL) due to risk of IgM flare 1
  • Use extended schedule (additional doses at weeks 12-16) for more durable response

Special Considerations

IgM Flare with Rituximab:

• Occurs in ~50% of patients during first months of treatment
• Not associated with treatment failure but can cause hyperviscosity
• Consider prophylactic plasmapheresis before rituximab in patients with IgM >4000 mg/dL 1

Hyperviscosity Management:

• Immediate plasmapheresis for symptomatic hyperviscosity
• Always combine with definitive therapy 1

Treatment for Relapsed/Refractory Disease

For patients with remission lasting >24 months, consider retreatment with the same regimen 1.

For patients with shorter remissions or resistance to first-line therapy:

1. Ibrutinib-Rituximab (category 1 recommendation) 1
2. Zanubrutinib (category 1 recommendation) 1
3. Bendamustine-Rituximab if not used previously 1
4. Bortezomib-Dexamethasone-Rituximab 1
5. Carfilzomib-based therapy (neuropathy-sparing proteasome inhibitor option) 1

Monitoring During Treatment

• Regular assessment of IgM levels
• Complete blood counts
• Renal and hepatic function tests
• Neurological evaluation if on neurotoxic agents
• Visual acuity testing if using specific agents with ocular toxicity potential

Pitfalls and Caveats

1. Rituximab-induced IgM flare:

   • Can be mistaken for disease progression
   • May persist for several months
   • Consider prophylactic plasmapheresis in patients with high baseline IgM

2. Ibrutinib discontinuation:

   • Abrupt stopping can lead to IgM rebound and decreased hemoglobin
   • Should not be interpreted as treatment failure 1

3. Bendamustine toxicity:

   • Higher risk of infections
   • Consider prophylactic antimicrobials
   • Dose reduction needed in elderly and those with renal impairment 1

4. Bortezomib-induced neuropathy:

   • Use subcutaneous route and weekly dosing to minimize risk
   • Monitor closely for early signs of neuropathy

By following these evidence-based recommendations, clinicians can effectively manage patients with Waldenström Macroglobulinemia (Bandiplus) while minimizing treatment-related complications and optimizing outcomes.