Decrease in CD4+ T-cell counts in patients with multiple myeloma treated with bortezomib.
BACKGROUND
Bortezomib is highly effective in multiple myeloma and is widely used in this disease. Recently, an increased incidence of varicella zoster virus (VZV) reactivation was reported in patients with myeloma undergoing bortezomib treatment.


METHODS
We investigated the influence of bortezomib on T-cell subpopulations in 53 patients with myeloma before initiation of bortezomib and during therapy.


RESULTS
A decrease of CD4+ T cells was seen in 41 of 53 patients (77%). The median CD3+/CD4+ lymphocyte counts declined from 494/microL (range, 130-2187/microL) to 274/microL (range, 41-1404/microL) during bortezomib treatment (P < .001). In the majority of patients (40 of 53 patients, 75%), CD4+ lymphocytes dropped to < 400/microL during bortezomib treatment, and in 18 of 53 patients (33.9%) the CD4+ T cells fell below 200/microL. The minimum CD4S+ cell count was observed at a median of 6 weeks (range, 2-22 weeks) after initiation of treatment. The incidence of herpes zoster reactivation was 5.7% in the whole population of patients with myeloma receiving bortezomib. Nineteen of 53 patients received acyclovir at a dose of 400 mg daily as prophylaxis against VZV reactivation. In this group, none of the patients developed herpes zoster. The incidence of VZV reactivation in patients not receiving acyclovir was 3 of 34 (8.8%). Importantly, occurrence of herpes zoster was associated with reduced CD4+ T-cell subpopulation: all patients who developed herpes zoster had CD4+ lymphocytes < 400/microL.


CONCLUSIONS
Our results show that bortezomib leads to a transient decrease in CD4+ lymphocytes, accompanied by an increased incidence of VZV infections. The antiviral prophylaxis with acyclovir is effective in patients with myeloma treated with bortezomib.
Heider
Ulrike
U
Department of Hematology and Oncology, Charité-Universitätsmedizin Berlin, Germany.
Rademacher
Jessica
J
Kaiser
Martin
M
Kleeberg
Lorenz
L
von Metzler
Ivana
I
Sezer
Orhan
O
D000212:Acyclovir / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001897:Boronic Acids; D000069286:Bortezomib; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D006562:Herpes Zoster / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D014645:Herpesvirus 3, Human / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D011719:Pyrazines; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D000212:Acyclovir