Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study.
OBJECTIVE
The aim of this subset analysis was to determine if bortezomib treatment is associated with increased incidence of varicella-zoster virus (VZV) reactivation in patients with relapsed multiple myeloma (MM).


METHODS
Incidence of herpes zoster was evaluated in 663 patients with relapsed MM from the phase III APEX trial comparing single-agent bortezomib with high-dose dexamethasone.


RESULTS
Bortezomib was associated with a significantly higher incidence of herpes zoster compared with dexamethasone treatment (13%, 42 of 331 v 5%, 15 of 332; P = .0002). Most herpes zoster infections were grade 1/2; incidences of grade 3/4 events (1.8% v 1.5%) and infections considered serious adverse events (1.5% v 0.9%) were similar between treatment arms, and no herpes zoster-related deaths occurred. Neither the time to onset of the herpes event nor the patients' absolute lymphocyte counts at baseline differed significantly between arms. VZV reactivation was the only herpes viral event noted to be significantly elevated in the bortezomib treatment group compared with the dexamethasone treatment group (P = .0002). The incidence of non-VZV-related herpes viral infections was comparable between arms. No additional risk factors for herpes zoster reactivation were identified.


CONCLUSIONS
Further studies are needed to explain these observations and their implications; however, for patients treated with bortezomib or bortezomib-containing regimens, the risk of VZV reactivation should be monitored and routine use of antiviral prophylaxis considered.
Chanan-Khan
Asher
A
Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA. asher.chanan-khan@roswellpark.org
Sonneveld
Pieter
P
Schuster
Michael W
MW
Stadtmauer
Edward A
EA
Facon
Thierry
T
Harousseau
Jean-Luc
JL
Ben-Yehuda
Dina
D
Lonial
Sagar
S
Goldschmidt
Hartmut
H
Reece
Donna
D
Neuwirth
Rachel
R
Anderson
Kenneth C
KC
Richardson
Paul G
PG
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology; D001897:Boronic Acids / Q000009:adverse effects* / Q000494:pharmacology; D000069286:Bortezomib; D006562:Herpes Zoster / Q000139:chemically induced*; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000009:adverse effects* / Q000494:pharmacology; D012008:Recurrence; D014775:Virus Activation / Q000187:drug effects
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib