What is the recommended treatment for shingles in patients with Waldenström's Macroglobulinemia (WM)?

Treatment of Shingles in Waldenström's Macroglobulinemia Patients

Patients with Waldenström's macroglobulinemia (WM) receiving treatment, particularly those on bortezomib-based regimens or BTK inhibitors, require antiviral prophylaxis against herpes zoster (shingles), and if shingles develops, should be treated with standard antiviral therapy (acyclovir, valacyclovir, or famciclovir) while carefully managing their immunosuppressive WM therapy.

Risk Context in WM Patients

WM patients face elevated herpes zoster risk due to:

• Immunosuppression from the underlying disease itself, which causes immune dysfunction through lymphoplasmacytic infiltration 1
• Chemotherapy-induced immunosuppression, particularly with regimens containing rituximab, alkylating agents, or nucleoside analogues 1
• Bortezomib therapy, which specifically increases herpes zoster reactivation risk and mandates prophylaxis 1
• BTK inhibitor therapy (ibrutinib, zanubrutinib), which impairs B-cell and innate immune function 1

Prophylaxis Recommendations

For patients on bortezomib-containing regimens:

• Antiviral prophylaxis against herpes zoster is strongly recommended throughout treatment 1
• This applies whether bortezomib is given weekly or twice-weekly, intravenously or subcutaneously 1

For patients on other immunosuppressive regimens:

• Consider prophylaxis for those receiving intensive chemoimmunotherapy combinations (bendamustine-rituximab, DRC, nucleoside analogue-based regimens) 1
• BTK inhibitor recipients should be monitored closely given their prolonged immunosuppression 1

Treatment of Active Shingles

When shingles develops in a WM patient:

Antiviral therapy:

• Initiate standard antiviral treatment immediately (acyclovir 800 mg 5 times daily, valacyclovir 1000 mg 3 times daily, or famciclovir 500 mg 3 times daily for 7-10 days)
• Start within 72 hours of rash onset for maximum efficacy
• Consider IV acyclovir for disseminated disease or immunocompromised patients with severe infection

WM therapy modifications:

• Temporarily hold bortezomib if active shingles develops, as continued proteasome inhibition during acute infection increases complications 1
• Consider holding rituximab during acute infection given its B-cell depleting effects 1
• BTK inhibitors may need temporary interruption depending on infection severity, though this must be weighed against risk of WM progression 1
• Resume WM therapy once shingles lesions have crusted and acute infection is controlled

Key Clinical Pitfalls

Common errors to avoid:

• Failing to provide herpes zoster prophylaxis when initiating bortezomib—this is a mandatory intervention 1
• Continuing full-dose immunosuppressive therapy during active disseminated zoster infection
• Inadequate monitoring for post-herpetic neuralgia in patients who already have baseline WM-related neuropathy 1
• Confusing WM-related neuropathy with early zoster-related pain—maintain high clinical suspicion for dermatomal pain patterns 1

Special consideration for neuropathy:

• WM patients commonly have baseline neuropathy from disease or treatment (particularly bortezomib) 1
• Post-herpetic neuralgia may be more severe and prolonged in this population
• Neurologist consultation is strongly recommended for complex neuropathy cases 1