Decrease in CD4+ T Cells in Multiple Myeloma Patients Receiving Bortezomib.
Authors: Heider Ulrike , Rademacher Jessica , Kaiser Martin , von Metzler Ivana , Marquardt Karin , Sezer Orhan 
Published: October 2019

Abstract
Abstract 3865
Poster Board III-801
The proteasome inhibitor bortezomib is highly effective in multiple myeloma and widely used in this disease. Recently, an increased incidence of opportunistic infections, particularly varicella zoster virus (VZV) reactivation (herpes zoster), was reported in myeloma patients undergoing treatment with bortezomib. We therefore analyzed the influence of bortezomib on lymphocyte subsets, particularly T-cell subpopulations, in the peripheral blood of myeloma patients before initiation and during the treatment. In addition, the results were correlated with the incidence of VZV reactivation. Peripheral blood samples from 53 multiple myeloma patients treated with bortezomib were collected. Eight of the patients were previously untreated and received bortezomib as front-line therapy, whereas 45 patients were treated in the relapse setting. Different subsets of lymphocytes in the peripheral blood were analyzed by four-color flow cytometry. A decrease of CD4+ T-cells was seen in 42/53 patients (77%). The median numbers of CD4+ T-cells decreased by 45% from 494/μl (range 130-2187) to 274/μl (range 41-1404) during therapy with the proteasome inhibitor (p < 0.001). In the majority of the patients (76%), CD4+ lymphocytes dropped to < 400/μl during bortezomib treatment, and in 18/53 patients (33.9%) the CD4+ T cells fell below 200/μl. The minimum CD4+ cell count was seen at a medium of 6 weeks (range 2-22) after the initiation of treatment, but recovered within a few weeks. The median number of circulating CD3+/CD8+ T-cells decreased by 33.6% from 420/μl (range 48-1518) to 279/μl (range 19-1693) during bortezomib therapy (p < 0.001). This was accompanied by a slight decrease of the median CD4/CD8 ratio from 1.17 (range 0.23-6.0) to 1.0 (range 0.15-4.18). Importantly, all of the patients receiving bortezomib as first-line treatment had a normal CD4+ lymphocyte count before initiation of treatment, and all of them showed a decrease of CD3+/ CD4+ cells during the therapy. The median number of circulating CD4+ T-cells in this subgroup decreased by 70% from 924/μl (range 479-1579) to 276/μl (range 80-626) (p < 0.01). The incidence of herpes zoster reactivation was 5.3% in the whole population of myeloma patients receiving bortezomib. 19/53 patients received acyclovir at a dose of 400mg 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 3/34 (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/μl. In conclusion, 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 myeloma patients treated with bortezomib.

Disclosures:
No relevant conflicts of interest to declare.