Abstract
Abstract
Bortezomib has been used for patients with relapsed or refractory multiple myeloma. However, considering most patients with multiple myeloma are elderly people, the management of bortezomib-induced adverse effects became important. Varicella zoster virus (VZV) reactivation was reported as another adverse event associated with bortezomib in the APEX trial. Although some concomitantly administered drugs such as steroid may induce herpes zoster, proteasome inhibition itself may be associated with VZV reactivation because NF-κB inactivation may reduce antiviral response, and proteasome inhibition may affect the cellular localization of VZV leading to nuclear accumulation of VZV. Therefore, we analyzed the incidence of VZV reactivation among 267 relapsed or refractory myeloma patients treated with bortezomib. All patients were treated with at least one kind of treatment other than bortezomib before bortezomib therapy. 58 cases of VZV reactivation was observed (21.72%, 58/267) during or after bortezomib treatment while only 25 cases were found during other treatments such as VAD, MP etc (9.36%, 25/267). The incidence of VZV reactivation was not different based on the type of regimen: bortezomib monotherapy (22.58%) vs. bortezomib combined with dexamethasone, alkylating agents or thalidomide (22.72%). The characteristics of patients were compared in table.
VZV reactivation (−) VZV reactivation (+) P value † number of prior VZV/total number of patients, ‡median (range), mean ± SD Age (median, range) 63 (43–82) 63 (37–82) n. s. Gender (male: female) 129:80 32:26 n. s. Number of prior zoster† 20/209 5/58 n. s. Disease duration (mean± SD) 3.57±3.01 years 2.33±1.99 years < 0.05 Number of prior treatment‡ 3 (1–7), 2.68±1.29 3 (1–7), 2.57±1.22 n. s.
The incidence of VZV reactivation was not related with the disease (D-S stage, type), health status (performance status, co-morbidity, social history, blood cell counts), and other toxicity associated with bortezomib. The median time and mean cycles to the onset of VZV reactivation after the first infusion of bortezomib were 46 days (7–560 days), and 2.58±1.97 cycles. Localized herpes zoster was dominant form, and most cases showed a good response to anti-viral therapeutics without significant sequela. In conclusion, bortezomib was associated with high incidence of VZV reactivation. However, considering the absence of factors predicting VZV reactivation, further study should be warranted to determine the routine use of anti-viral prophylaxis.