Acyclovir To Prevent Herpes Zoster in Myeloma Patients Treated with Bortezomib.

While the major immune impairment in myeloma is humoral (hypogammaglobulinemia), cell-mediated immunity (CMI) is also impaired. CMI abnormalities include defective generation of cytotoxic T cells and impaired response to mitogens. Treatment also suppresses CMI. Reactivation of the varicella zoster virus (VZV) with development of herpes zoster (shingles) is a consequence of suppressed CMI. The pain associated with post-herpetic neuralgia can be severe, prolonged and disabling, and compromises quality of life dramatically. Because of this, it has been our long-standing policy to place all myeloma patients on indefinite prophylactic anti-viral agents once disease-specific therapy is initiated. The table below shows our standard anti-viral drug regimens for prevention of VZV reactivation.

The acyclovir dose is increased to 400 mg thrice a day for a few weeks after intensive combination chemotherapy or high-dose melphalan-autotransplantation to prevent herpes simplex stomatitis. Development of VZV reactivation on this strategy has been exceptional, and the few breakthrough zoster episodes have always been associated with discontinuation of prophylaxis by the patient. Concern has been raised recently about development of zoster in myeloma patients receiving bortezomib. We undertook a retrospective review to see if zoster has been seen in myeloma patients while on acyclovir prophylaxis. The study population consisted of bortezomib-treated patients (n=125) who received all of their therapy at Northwestern over the last 3 years, and who were followed at least once a month during therapy. A detailed medication history was taken at each visit to ensure compliance. Patients who received all or part of their therapy elsewhere and were seen less frequently, a much larger population, were excluded. Patients received bortezomib either in the standard manner (days 1, 4, 8 and 11 every 21 days) or on a once-weekly schedule. The duration of bortezomib therapy was 1–164 weeks (median 16 weeks). The total duration of bortezomib therapy was 4150 weeks (80 patient-years). Except for the occasional missed dose (forgetting or running out of medication), the self-reported compliance with anti-viral prophylaxis was 100%. Not a single episode of herpes zoster was seen during this period. No adverse effects were seen that could be definitely attributed to acyclovir, valaciclovir or famciclovir. This finding was consistent with our observation of lack of VZV reactivation in myeloma patients on other regimens commonly used at our center such as pulse dexamethasone, thalidomide and combinations, lenalidomide and combinations, CDEP and DT-PACE combination chemotherapy, and high-dose melphalan with autotransplantation - as long as they are on anti-viral prophylaxis. We conclude that daily acyclovir (or a suitable alternative) is virtually universally effective at preventing herpes zoster in patients with myeloma who are on bortezomib or bortezomib-containing regimens. Despite the lack of a prospective randomized study, we suggest that long-term acyclovir prophylaxis should employed universally in myeloma patients once disease-specific therapy is started. The live-attenuated zoster vaccine (Zostavax®) is contraindicated in immunocompromised patients, and should not be used as an alternative to prevent shingles in myeloma.