Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial.
Winston Drew J,Mullane Kathleen M,Cornely Oliver A,Boeckh Michael J,Brown Janice Wes,Pergam Steven A,Trociukas Igoris,Žák Pavel,Craig Michael D,Papanicolaou Genovefa A,Velez Juan D,Panse Jens,Hurtado Kimberly,Fernsler Doreen A,Stek Jon E,Pang Lei,Su Shu-Chih,Zhao Yanli,Chan Ivan S F,Kaplan Susan S,Parrino Janie,Lee Ingi,Popmihajlov Zoran,Annunziato Paula W,Arvin Ann,
Lancet (London, England)
BACKGROUND:Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. METHODS:In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age (<50 vs ≥50 years) and intended duration of antiviral prophylaxis after transplantation (≤3 months vs >3 to ≤6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5-60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all randomised participants who received at least one dose of vaccine and had follow-up data. A prespecified vaccine efficacy success criterion required the lower bound of the 95% CI be higher than 25% for the relative reduction of the hazard ratio of herpes zoster infection in participants given the vaccine from one of the consistency lots compared with those given placebo. This trial is registered on ClinicalTrials.gov (NCT01229267) and EudraCT (2010-020150-34). FINDINGS:Between Dec 7, 2010, and April 25, 2013, 560 participants were randomly assigned to the vaccine consistency lot group, 106 to the high-antigen lot group, and 564 to the placebo group. 249 (44%) of patients in the vaccine consistency lot group, 35 (33%) in the high-antigen lot group, and 220 (39%) in the placebo group discontinued before study end, mostly because of death or withdrawal. 51 participants were excluded from the primary efficacy endpoint analyses because they did not undergo auto-HSCT or were not vaccinated, or both (22 [4%] in the vaccine consistency lot group, and 29 [5%] in the placebo group). Mean follow-up for efficacy was 2·4 years (SD 1·3) in the vaccine consistency lot group and 2·3 years (SD 1·3) in the placebo group. 42 (8%) of 538 participants in the vaccine consistency lot group (32·9 per 1000 person-years) and 113 (21%) of 535 in the placebo group (91·9 per 1000 person-years) had a confirmed case of herpes zoster. The estimated vaccine efficacy was 63·8% (95% CI 48·4-74·6), meeting the pre-specified success criterion. For the combined vaccine groups versus the placebo group, the proportion of patients with serious adverse events (216 [33%] of 657 vs 181 [33%] of 554; risk difference 0·2%, 95% CI -5·1 to 5·5) and serious vaccine-related adverse events (five [1%] vs five [1%]; risk difference 0·1%, -1·4 to 1·1) were similar. Vaccine-related injection-site adverse events occurred more frequently in participants given vaccine than those given placebo (191 [29%] vs 36 [7%]; risk difference 22·6%, 95% CI 18·5-26·6; p<0·0001). INTERPRETATION:This study shows for the first time in a large phase 3 trial that early vaccination of auto-HSCT recipients during the peri-transplant period can be effective for the prevention of an opportunistic infection like herpes zoster and that the vaccine is well tolerated. FUNDING:Merck & Co., Inc.
10.1016/S0140-6736(18)30631-7
Varicella zoster virus reactivation after autologous SCT is a frequent event and associated with favorable outcome in myeloma patients.
Kamber C,Zimmerli S,Suter-Riniker F,Mueller B U,Taleghani B M,Betticher D,Zander T,Pabst T
Bone marrow transplantation
The occurrence of varicella zoster virus (VZV) reactivation is increased after allogeneic transplantation, whereas limited data are available for herpes zoster (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic significance of HZ and its correlation with VZV serology in 191 consecutive myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was assessed as high or rather high in 70% of the patients. By immune fluorescence and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV antibodies at ASCT. Lower specific antibody titers at transplantation were observed in patients with HZ after ASCT than in those without reactivation (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared with patients without HZ (P=0.007). Our data indicate that VZV reactivation after ASCT is a frequent event carrying a significant disease burden and it is associated with improved survival. Low levels of specific VZV antibodies at ASCT suggest increased vulnerability for VZV reactivation.
10.1038/bmt.2014.290
Daily 500 mg valacyclovir is effective for prevention of Varicella zoster virus reactivation in patients with multiple myeloma treated with bortezomib.
Fukushima Toshihiro,Sato Tomomi,Nakamura Takuji,Iwao Haruka,Nakajima Akio,Miki Miyuki,Sakai Tomoyuki,Kawanami Takafumi,Sawaki Toshioki,Fujita Yoshimasa,Tanaka Masao,Masaki Yasufumi,Okazaki Toshiro,Nakajima Hideo,Motoo Yoshiharu,Umehara Hisanori
Anticancer research
BACKGROUND:In patients with multiple myeloma (MM), bortezomib is associated with a significant risk of Varicella zoster virus (VZV) reactivation. There are some reports that acyclovir reduces the risk of VZV reactivation. We assessed whether VZV reactivation could be reduced by using prophylactic valacyclovir at a dose of 500 mg daily. PATIENTS AND METHODS:We retrospectively evaluated 32 patients with MM who received bortezomib and valacyclovir prophylaxis at the Kanazawa Medical University Hospital. Patients received valacyclovir prophylaxis orally at a dose of 500 mg daily, without cessation during bortezomib treatment. RESULTS:The median age was 69 years (range=45-90 years). Fifteen patients were male and seventeen were female. The median bortezomib dose was 37.0 mg/m(2) (range=5.2-167.6 mg/m(2)). All patients also received corticosteroids. The median duration of valacyclovir prophylaxis was 301 days (range=24-1206 days) and the median valacyclovir dose was 150.5 g (range=12-603 g). VZV reactivation developed in only one patient during valacyclovir prophylaxis. VZV reactivation did not develop in three patients who had a past history of VZV reactivation without valacyclovir prophylaxis. Adverse events over grade 3 associated with valacyclovir were not observed. CONCLUSION:Valacyclovir at a dose of 500 mg daily appears to be effective at preventing VZV reactivation and was well-tolerated by patients with MM who received bortezomib.
Bortezomib and bilateral herpes zoster.
di Meo Nicola,Bergamo Serena,Dondas Adina,Trevisan Giusto
Acta dermatovenerologica Alpina, Pannonica, et Adriatica
Bortezomib is a proteasome inhibitor that has proven to be a very effective treatment for multiple myeloma. There is considerable debate about the potential for reactivation of the varicella zoster virus (VZV) in patients with multiple myeloma during treatment with bortezomib. This report describes the case of a 70-year-old patient with multiple myeloma that developed bilateral herpes zoster shortly after being treated with bortezomib. Furthermore, it emphasizes the importance of using an antiviral prophylaxis with acyclovir in these patients treated with bortezomib.
Varicella zoster virus reactivation reported with isatuximab use.
Journal of chemotherapy (Florence, Italy)
Isatuximab is a CD38-directed antibody indicated for the treatment of relapsed or refractory multiple myeloma. The Division of Pharmacovigilance at the U.S. Food and Drug Administration (FDA) reviewed case reports from postmarketing sources, including the FDA Adverse Event Reporting System (FAERS), PubMed, and Embase, to investigate a potential association between isatuximab and the risk of varicella zoster virus (VZV) reactivation. We identified 20 reports of which 15 met our case definition and causality criteria. All 15 patients (80% male, median age = 60 years) received isatuximab for a hematologic neoplasm; eight (53%) for previously untreated multiple myeloma. All cases described additional risk factors for VZV reactivation, including concomitant proteasome inhibitor and/or immunomodulatory drug ( = 10, 67%) use. Based on this postmarket analysis, the U.S. Prescribing Information for isatuximab was updated to include this new safety information, including recommendations for antiviral prophylaxis.
10.1080/1120009X.2023.2266201
[Systemic varicella-zoster infection during ixazomib-containing multiagent chemotherapy for multiple myeloma].
Nakayama Hitomi,Kato Jun,Kikuchi Taku,Okayama Mikio,Kamiya Takahiro,Mizuno Kota,Shimizu Takayuki,Okamoto Shinichiro,Mori Takehiko
[Rinsho ketsueki] The Japanese journal of clinical hematology
A 58-year-old man received high-dose melphalan with autologous peripheral blood stem cell transplantation for multiple myeloma in stringent complete response (sCR). Relapse occurred 4 years after the transplantation, and he was placed on ixazomib, lenalidomide, and dexamethasone (IRd) and achieved sCR. On the 10th day of the 10th course of IRd, he developed fever followed by generalized skin eruption with vesicles, headache, and dizziness. Varicella-zoster virus (VZV) antigen from the vesicle and VZV-DNA from the cerebrospinal fluid were detected, and he was diagnosed with systemic VZV infection. He was placed on intravenous acyclovir (ACV), and the infection resolved completely. VZV infection has been recognized as an important complication associated with the use of proteasome inhibitors; however, to our knowledge, there have been no reported cases of serious systemic VZV infection associated with ixazomib. The clinical course of this case strongly suggests the importance of prophylaxis for VZV infection during treatment with ixazomib.
10.11406/rinketsu.61.870
Varicella-zoster virus prophylaxis with low-dose acyclovir in patients with multiple myeloma treated with bortezomib.
Pour Ludek,Adam Zdenek,Buresova Lucie,Krejci Marta,Krivanova Andrea,Sandecka Viera,Zahradova Lenka,Buchler Tomas,Vorlicek Jiri,Hajek Roman
Clinical lymphoma & myeloma
BACKGROUND:Varicella-zoster virus (VZV) reactivation is a common complication in patients with multiple myeloma (MM) treated with bortezomib, with an incidence rate of 10%-60%. The aim of our study was to analyze the effect of acyclovir prophylaxis in this patient population. PATIENTS AND METHODS:We studied 98 consecutive patients with relapsed MM treated with bortezomib. Bortezomib 1.3 mg/m2 was given on days 1, 4, 8, and 11 of a 21-day cycle. At first, patients did not receive any VZV prophylaxis, but because of the high incidence of VZV reactivation, VZV prophylaxis with acyclovir was implemented subsequently. RESULTS:A total of 11 patients treated with bortezomib did not have any VZV prophylaxis, and 4 of these 11 patients (36%) developed VZV reactivation in the form of herpes zoster. No VZV reactivations were observed in the 32 patients who received acyclovir 400 mg 3 times daily or the 55 patients who received acyclovir in a dose reduced to 400 mg once daily during bortezomib treatment. CONCLUSION:Varicellazoster virus reactivation is a common and serious adverse effect of bortezomib treatment. Acyclovir 400 mg once daily is sufficient to protect from VZV reactivation in patients with MM treated with bortezomib.
10.3816/CLM.2009.n.036
Acyclovir prophylaxis against varicella zoster virus reactivation in multiple myeloma patients treated with bortezomib-based therapies: a retrospective analysis of 100 patients.
Swaika Abhisek,Paulus Aneel,Miller Kena C,Sher Taimur,Almyroudis Nikolaos G,Ball Donna,Wood Margaret,Masood Aisha,Lee Kelvin,Chanan-Khan Asher A
The journal of supportive oncology
BACKGROUND:Previous studies have indicated that, in patients with multiple myeloma (MM), bortezomib is associated with an increased incidence of herpes zoster, resulting from reactivation of latent varicella zoster virus (VZV). OBJECTIVE:Our objective was to determine whether increased risk of VZV reactivation could be abrogated by using prophylactic acyclovir. METHODS:We retrospectively evaluated 100 consecutive MM patients treated with bortezomib-based therapies at the Roswell Park Cancer Institute for development of herpes zoster. Frontline and relapsed/refractory patients were included, and patients received bortezomib alone or in combination with agents such as doxorubicin, melphalan, or dexamethasone. All patients received >4 weeks of acyclovir prophylaxis (400 mg twice daily), which was initiated prior to starting treatment with bortezomib and discontinued 4 weeks following bortezomib. RESULTS:Median patient age was 62 years, 57% were male, and most (56%) had Durie-Salmon stage IIIA MM. None of the 100 MM patients receiving acyclovir prophylaxis developed herpes zoster during treatment with bortezomib, irrespective of patients receiving a wide variety of concomitant antimyeloma therapies and regardless of response to bortezomib-based therapy. One additional patient, found to be noncompliant with acyclovir therapy, experienced VZV reactivation, having received 3 cycles of bortezomib (3 weeks each cycle) in combination with cyclophosphamide and dexamethasone. LIMITATIONS:Limitations of the study include its small size and retrospective nature. CONCLUSIONS:The increased risk of VZV reactivation observed in previous studies of bortezomib-based therapy was completely abrogated in this series of patients who received prophylaxis with acyclovir.
10.1016/j.suponc.2011.10.006
Analysis of herpes zoster events among bortezomib-treated patients in the phase III APEX study.
Chanan-Khan Asher,Sonneveld Pieter,Schuster Michael W,Stadtmauer Edward A,Facon Thierry,Harousseau Jean-Luc,Ben-Yehuda Dina,Lonial Sagar,Goldschmidt Hartmut,Reece Donna,Neuwirth Rachel,Anderson Kenneth C,Richardson Paul G
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
PURPOSE: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). PATIENTS AND 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. CONCLUSION: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.
10.1200/JCO.2007.14.9641
Incidence, risk factors, and implemented prophylaxis of varicella zoster virus infection, including complicated varicella zoster virus and herpes simplex virus infections, in lenalidomide-treated multiple myeloma patients.
König C,Kleber M,Reinhardt H,Knop S,Wäsch R,Engelhardt M
Annals of hematology
In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients' data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings-and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols-we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and-in those centers facilitating a research data warehouse-advocate an analogue data review as an appropriate multicenter approach.
10.1007/s00277-013-1951-6
The risk factors for herpes zoster in bortezomib treatment in patients with multiple myeloma.
Yi Yang-Seon,Chung Joo-Seop,Song Moo-Kon,Shin Ho-Jin,Seol Young-Mi,Choi Young-Jin,Cho Goon-Jae,Lee Gyeong-Won,Moon Joon-Ho,Hwang In-Hye,Ahn Kang-Hee,Lee Hee-Sun,Shin Kyung-Hwa,Hwang Jong-Min
The Korean journal of hematology
BACKGROUND:Bortezomib has significant activity in treating multiple myeloma (MM). The risk of herpes zoster (HZ) has been reported to increase significantly with bortezomib treatment, but the predisposing factors for HZ are not clear. This study is a retrospective analysis of the relevant risk factors for HZ in Korean MM patients treated with bortezomib. METHODS:Sixty-six patients with refractory or relapsed MM who underwent chemotherapy with bortezomib were included in the study. Prophylactic antiviral drugs were not used for treatment. The following parameters were reviewed: age, gender, stage and type of MM, extent of previous treatment, history of HZ, duration from the time of diagnosis to the time of bortezomib treatment initiation, and absolute lymphocyte counts (ALC) at the time of bortezomib treatment initiation. RESULTS:The incidence of HZ was 16.7%. There were no intergroup differences between the HZ-positive and the HZ-negative groups with regard to a history of HZ, number of previous treatments, and exposure to steroids before bortezomib treatment. The median duration from the time of MM diagnosis to the time of bortezomib treatment initiation in the HZ-positive group was significantly shorter than that in the HZ-negative group. The median ALC at the time of bortezomib initiation in the HZ-positive group was significantly lower than that in the HZ-negative group. CONCLUSION:Bortezomib itself might act as a risk factor for HZ by inhibiting cell-mediated immunity, and patients with low ALC at the time of bortezomib treatment initiation were at greater risk of HZ during bortezomib treatment.
10.5045/kjh.2010.45.3.188
Low-dose acyclovir is effective for prevention of herpes zoster in myeloma patients treated with bortezomib: a report from the Korean Multiple Myeloma Working Party (KMMWP) Retrospective Study.
Kim Seok Jin,Kim Kihyun,Do Young Rok,Bae Sung Hwa,Yang Deok-Hwan,Lee Je-Jung
Japanese journal of clinical oncology
OBJECTIVE:Acyclovir prophylaxis has been considered as mandatory for patients receiving bortezomib because herpes zoster is a common adverse event associated with the use of bortezomib. Although the minimal effective dose of acyclovir for prophylaxis has not yet established, the efficacy of low-dose acyclovir prophylaxis, 400 mg once daily, has been suggested. METHODS:We retrospectively reviewed the patients receiving the low-dose acyclovir which was defined as the once daily administration of acyclovir 400 or 200 mg. All patients received bortezomib-containing chemotherapy in the setting of relapsed or refractory myeloma. RESULTS:Eighty patients received bortezomib-containing treatment as a salvage therapy. All patients received at least one or more treatments prior to bortezomib treatment, including autologous stem cell transplantation. Sixty-one patients received 400 mg of acyclovir once daily while 19 patients received 200 mg. Although seven cases of herpes zoster were observed from 80 patients (7/80, 8.75%), two cases of herpes zoster received 400 mg during the limited period from the first to the fourth cycle, and the other five received 200 mg. Therefore, there was no herpes zoster in patients who received 400 mg of acyclovir till the last cycle of bortezomib treatment. There were no adverse events associated with the use of acyclovir prophylaxis. CONCLUSIONS:The administration of acyclovir 400 mg once daily during the bortezomib treatment is an effective prophylaxis for herpes zoster in patients receiving bortezomib irrespective of disease state and the type of chemotherapy regimen.
10.1093/jjco/hyq194
Herpes zoster after autologous hematopoietic stem cell transplantation.
Santos Kelli Borges Dos,Souza Rafaela Souto E,Atalla Angelo,Hallack-Neto Abrahão Elias
Revista brasileira de hematologia e hemoterapia
BACKGROUND:The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. METHODS:A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. RESULTS:Fourteen (6.1%) patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3%) were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value=0.002). There were no significant differences for the other variables analyzed. CONCLUSION:The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.
10.1016/j.bjhh.2016.05.015
Importance of Compliance With Guidelines for the Prevention of Varicella-Zoster Virus Reactivation in Multiple Myeloma.
Ohashi Yasukata,Yatabe Megumi,Niijima Daisuke,Imamura Arina,Nagayama Yoshiyuki,Otsuka Kentaro,Yachi Yutaka,Ueno Hironori,Yano Takahiro,Mori Nobuaki,Higai Koji,Yokoyama Akihiro
In vivo (Athens, Greece)
BACKGROUND/AIM:The importance of compliance with National Comprehensive Cancer Network (NCCN) guidelines for preventing varicella-zoster virus reactivation (VZVr) in multiple myeloma (MM) in a clinical setting has not been well investigated. PATIENTS AND METHODS:We retrospectively studied the clinical characteristics and outcomes of 118 patients with MM treated with proteasome inhibitors. RESULTS:Thirty-nine episodes of VZVr were observed in 37 patients (VZVr group). The proportion of prophylactic antiviral prescriptions and compliance with antiviral prophylaxis based on the NCCN Clinical Practice guidelines was 76% and 30% in the VZVr group, and 88% and 74% in the non-VZVr group, respectively. Multivariate analysis showed that compliance with the NCCN guidelines was the only independent risk factor for VZVr (p=0.0017). CONCLUSION:It is important that prophylactic antivirals are prescribed for an appropriate duration of time to prevent the reactivation of VZV in compliance with existing guidelines.
10.21873/invivo.12624
Expression and correlation of IL-2, IL-10 and TNF-α in patients with multiple myeloma-infected herpes zoster treated by bortezomib-containing regimen.
Liu Kang,Yin Yafei,Zhou Xinfu,Zhu Kaibo,Luo Zimian
American journal of translational research
BACKGROUND:Multiple myeloma (MM) is a proliferative disease with complex pathogenesis. Most patients will have low body resistance and high inflammatory mediators. Bortezomib is an anti-tumor drug. There are few reports on the clinical efficacy and adverse reactions of bortezomib intervention. This research aimed to explore the effect of bortezomib on inflammation and immune lymphocytes of patients with MM-infected herpes zoster. OBJECTIVE:The aim of this study is to explore the effect of bortezomib on inflammation and immune lymphocytes, i.e. the expression and correlation of interleukin (IL)-2, IL-10 and tumor necrosis factor-α (TNF-α) in patients with MM-infected herpes zoster (HZ) receiving bortezomib-containing regimen. METHODS:From October 2017 to March 2020, 83 MM patients receiving bortezomib-containing regimen were analyzed retrospectively, patients were divided into infection group (28 cases, IG) and non-infection group (55 cases, NG) based on whether or not they are complicated with HZ Pre- and post-treatment. IL-2, IL-10, TNF-α and immune lymphocytes (CD3, CD4, CD8) were tested by AimPlex multifactor flow detection technique, and the Eastern Cooperative Oncology Group (ECOG) performance status scores were compared before therapy. The independent risk factors of patients receiving bortezomib-containing regimen were analyzed via multivariate logistic regression. RESULTS:After therapy, serum IL-2 and TNF-α declined significantly in NG while changed insignificantly in IG. Compared with NG, serum CD3 and CD4 in IG increased after treatment, while CD8 decreased significantly. Before therapy, ECOG score in IG was higher than that in NG. Correlation analysis showed that IL-2 and TNF-α were negatively correlated with CD3 and CD4, and positively correlated with CD8 and ECOG score. IL-10 was the opposite. Multivariate logistic regression analysis identified the independence of declined CD3, CD4, CD8 and IL-10, increased IL-2, TNF-α and ECOG score before treatment as risk factors for HZ. CONCLUSION:MM patients have a high incidence of HZ. Before treatment, lymphocytopenia, increased IL-2, TNF-α and decreased IL-10 are important risk factors for HZ.
Varicella-zoster virus-specific cell-mediated immunity and herpes zoster development in multiple myeloma patients receiving bortezomib- or thalidomide-based chemotherapy.
Kim Ji-Won,Min Chang-Ki,Mun Yeung-Chul,Park Yong,Kim Byung Soo,Nam Seung-Hyun,Koh Youngil,Kwon Ji-Hyun,Choe Pyoeng Gyun,Park Wan Beom,Kim Inho
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
BACKGROUND:The incidence of herpes zoster is substantial during bortezomib treatment in patients with multiple myeloma (MM). OBJECTIVES:This study aimed to elucidate the effect of chemotherapy with or without bortezomib in MM patients on their herpes zoster incidence and varicella zoster virus (VZV)-specific cell-mediated immunity (CMI). STUDY DESIGN:Peripheral blood mononuclear cells were collected at baseline and after 1 month of bortezomib-based or thalidomide-based chemotherapy and then analyzed using VZV-specific interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay. The clinical data from these patients were analyzed in relation to the ELISPOT results. RESULTS:Of 58 patients analyzed, 39 patients received bortezomib and the other 19 patients, thalidomide. Among them, 5 patients developed herpes zoster during chemotherapy; all 5 were being treated with the bortezomib-based regimen and were not receiving prophylactic anti-viral agents. The median onset of herpes zoster was 32 days (range, 15-95 days) from the initiation of chemotherapy. Among patients who received bortezomib therapy, acyclovir prophylaxis significantly reduced the risk for herpes zoster (100-day cumulative incidence, 0% vs. 49.5%; p<0.001). Spot-forming cell (SFC) counts in the IFN-γ ELISPOT assay decreased from baseline after bortezomib (p=0.011) or thalidomide (p=0.096) treatment. Patients with baseline SFCs greater than 20/10(6) mononuclear cells exhibited significantly higher incidence of herpes zoster (100-day cumulative incidence, 34.8% vs. 0%; p=0.040). CONCLUSIONS:Bortezomib treatment significantly reduced VZV-specific CMI, and high baseline SFC counts in patients receiving this treatment without acyclovir prophylaxis were associated with a significantly increased risk for herpes zoster.
10.1016/j.jcv.2015.10.018
Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma.
Kim Seok Jin,Kim Kihyun,Kim Byung Soo,Lee Hyo-Jin,Kim Hawk,Lee Na-Ri,Nam Seung-Hyun,Kwon Jung Hye,Kim Hyo Jung,Sohn Sang Kyun,Won Jong-Ho,Lee Jae Hoon,Suh Cheolwon,Yoon Sung-Soo,Kim Hye Jin,Kim Inho,Do Young-Rok,Lee Won-Sik,Joo Young-Don,Shin Ho Jin,
Clinical lymphoma & myeloma
BACKGROUND:Bortezomib has significantly advanced the treatment of patients with multiple myeloma (MM). However, considering that most patients with MM are elderly, bortezomib-related morbidity should be thoroughly studied to ensure the safe use of this drug. Herpes zoster has been reported as a possible adverse event associated with bortezomib because a major target of bortezomib, nuclear factor-kappaB, is known to be involved with T-cell immunity. PATIENTS AND METHODS:We performed a retrospective analysis of the incidence of herpes zoster among 282 patients treated with a bortezomib-containing regimen. RESULTS:During the patients' pre-bortezomib treatment (median, 2.14 years), the incidence of herpes zoster was 11% (31 of 282 patients). However, after the patients were treated with bortezomib, the incidence increased to 22.3% (63 of 282 patients), of which almost all occurrences were within the first 3 cycles (median duration, 41 days). The time interval from diagnosis to bortezomib initiation date was shorter in herpes zoster-positive patients than in herpes zoster-negative patients (2.14 +/- 1.87 years vs. 3.38 +/- 2.95 years; P = .002). Disease duration, previous herpes zoster infection, disease stage and type of myeloma, and the type and intensity of previous treatments failed to show any relationship with herpes zoster. These findings suggest that longer history of disease and treatments did not affect the occurrence of herpes zoster, nor did the type of bortezomib regimens or their toxicities. CONCLUSION:Bortezomib can increase the incidence of herpes zoster regardless of disease duration, previous treatments, and concomitantly administered drugs. Thus, the occurrence of herpes zoster should be monitored during bortezomib treatment.
10.3816/CLM.2008.n.031
[Risk Factors and the Effect of Antiviral Prophylaxis for Herpes Zoster in Multiple Myeloma Patients].
Zhongguo shi yan xue ye xue za zhi
OBJECTIVE:To study the incidence and risk factors of herpes zoster in patients with multiple myeloma and to evaluate the preventive effect of antiviral therapy. METHODS:The clinical features of multiple myeloma patients with herpes zoster were retrospectively analyzed, the risk factors of herpes zoster and the effect of antiviral prophylaxis were analyzed. RESULTS:Among 180 patients with multiple myeloma, 23 cases developed herpes zoster (12.8%). The incidence of herpes zoster was 19.1% in patients with renal dysfunction and 23.5% after autologous hematopoietic stem cell transplantation (ASCT). The incidence of herpes zoster was higher in patients receiving bortezomib-containing regimens (21/137, 15.3%) than that in those without bortezomib (2/43, 4.7%), but there was no statistical difference ( =0.067). Antiviral prophylaxis was associated with fewer zoster infections, 8/111(7.2%) developed herpes zoster in patients who received antiviral prophylaxis, and 15/69 (21.7%) in those receiving no prophylaxis( =0.005). 65.2% of patients with herpes zoster did not receive antiviral prophylaxis. Multivariate analysis showed that bortezomib treatment, AHSCT and renal dysfunction were independent risk factors for multiple myeloma with herpes zoster, while antiviral prophylaxis was independently associated with reducing the risk of herpes zoster. Herpes zoster had no effect on OS in patients with multiple myeloma. CONCLUSION:The risk of herpes zoster in multiple myeloma patients was increased. Antiviral prophylaxis can reduce the risk of herpes zoster in patients on bortezomib-based therapy.
10.19746/j.cnki.issn.1009-2137.2024.01.027
Herpes zoster prophylaxis with low-dose acyclovir in patients with malignant lymphoma and multiple myeloma treated with autologous stem cell transplantation.
European journal of haematology
BACKGROUND:Herpes zoster (HZ) is a frequent complication after autologous stem cell transplantation (ASCT). The option of zoster prophylaxis with an antiviral drug is described in the literature, but there is no consensus on the drug and the dosage. PATIENTS AND METHODS:We analyzed the records of 310 patients treated with ASCT who were controlled regularly regarding HZ inter alia for at least 24 months following ASCT. Since 01/2015 patients received prophylactic low-dose acyclovir (400 mg per day) during the first 12 months following discharge after ASCT (n = 107). RESULTS:Twenty percent of patients without this kind of prophylaxis and 2.8% of patients with prophylaxis developed HZ (p < .001). No patient with this prophylaxis developed HZ in the first year after ASCT, 2.8% of patients in the second year after ASCT. A prognostic factor was the kind of diagnosis: 30% of lymphoma patients and 14% of myeloma patients developed HZ in the first 24 months after ASCT without prophylaxis, but only 6.3% and 0% of patients with prophylaxis, respectively. Neither an increase of HZ cases following prophylaxis nor acyclovir refractory HZ cases were observed. CONCLUSIONS:Zoster prophylaxis with low-dose acyclovir over 12 months after ASCT is effective and well tolerated.
10.1111/ejh.13810
[Analysis of Risk Factors of Herpes Zoster in Patients with Multiple Myeloma Treated with Bortezomib].
Zhongguo shi yan xue ye xue za zhi
OBJECTIVE:To explore and analyze the risk factors of herpes zoster in patients with multiple myeloma (MM) during the chemotherapy with bortezomib. METHODS:Clinical data of 85 MM patients treated with bontizomib from January 2015 to January 2019 were selected and divided into case group and control group accroding to the occurred of herpes zoster. The clinical characteristic, treatment outcome and related factor of herpes zoster were retrospective analyzed. RESULTS:Twenty of the 85 patients with MM treated with bortezomib developed herpes zoster occurred (23.5%). Single-factor analysis showed that age≥65 years, lymphocytopenia occurred before treatment, neutropenia occurred before treatment, ECOG score≥2, application of cyclophosphamide, absence of preventive antiviral therapy were associated with the genesis of herpes zoster (P＜0.05). Multivariate logistic regression analysis showed that lymphocytopenia occurred before treatment, the application of cyclophosphamide and the absence of preventive antiviral therapy were the independent risk factors for herpes zoster (P＜0.05). CONCLUSION:The incidence of herpes zoster is high in the multiple myeloma patients treated with bortezomib. Lymphocytopenia occurred before treatment, the application of cyclophosphamide, and the absence of prophylactic antiviral therapy are the important risk factors for herpes zoster, for which the clinicians should attach great importance.
10.19746/j.cnki.issn.1009-2137.2020.06.029
Efficacy of Intermittent, Oral Famciclovir Prophylaxis for Bortezomib-Induced Herpes Zoster in Multiple Myeloma Patients.
Zheng Gaofeng,Guan Fangshu,Han Xiaoyan,Yang Li,Zhao Yi,Yang Yang,Zhang Enfang,He Jingsong,He Donghua,Wu Wenjun,Huang He,Cai Zhen
Frontiers in oncology
Objective:To explore the efficacy and safety of intermittent, oral famciclovir prophylaxis for bortezomib-induced herpes zoster in multiple myeloma patients. Method:We retrospectively analyzed the incidence of bortezomib treatment-related varicella-zoster virus reactivation in 719 newly-diagnosed multiple myeloma patients receiving intermittent oral famciclovir prophylaxis, continuous oral acyclovir prophylaxis or no prophylaxis. The definition of intermittent oral famciclovir prophylaxis was oral famciclovir at a dose of 250mg twice daily for 9 days after finishing the last dose of bortezomib therapy every cycle. Age, gender, stage per the International Staging System, type of M protein, baseline of absolute lymphocyte count, absolute neutrophil count, and absolute monocyte count were analyzed to find the potential factors that could predispose to herpes zoster infections. Results:Varicella-zoster virus infection occurred in 96 patients (13.4%) during bortezomib treatment. The incidence of herpes zoster was significantly higher in the non-prophylaxis group compared with the prophylaxis group (22.9% vs 8.2% P<0.001), while the rate was similar between the intermittent oral famciclovir group and the continuous oral acyclovir group (8.4% vs 7.9% P=0.835). Hepatic and renal toxicity were observed in 12% and 2.8% of the patient respectively in the intermittent famciclovir group, which was similar in the continuous acyclovir group (18.1% and 4.2%). The prophylactic use of antiviral agents is a predictive factor for varicella-zoster virus reactivation. Conclusion:Intermittent famciclovir prophylaxis is effective and safe in preventing herpes zoster development and can markedly reduce the duration of oral medicine treatment compared with continuous acyclovir prophylaxis.
10.3389/fonc.2022.843032
Herpes zoster prophylaxis: Essential for treating newly diagnosed multiple myeloma patients.
Cancer medicine
BACKGROUND:Multiple myeloma (MM) is known for its immune disturbance and patients suffering from MM are thus vulnerable to opportunistic infections, including herpes zoster (HZ). As HZ infection remarkably affects patients' quality of life and poses huge economic burdens on the health system, we aim to identify the risk factors of HZ infection and evaluate the effects of different dosages, types, and durations of anti-HZ prophylaxis drugs to prevent HZ infection. METHODS:551 MM patients at Taipei Veterans General Hospital in Taiwan between January 1, 2009 and August 31, 2021 were restrospectively analyzed. The patients' baseline characteristics were recorded. The primary endpoint of the study was the incidence of HZ infection among the studied patient population. Due to the lack of cost coverage from Taiwanese public health insurance on HZ prophylaxis drugs, the use of anti-HZ drugs mainly depends on physicians' preferences and patients' choices. RESULTS:In our study, prophylaxis was given to 283 of the patients. In the multivariate analysis, we included non-prophylaxis, age ≥ 60, corrected serum calcium ≥12 mg/dl, serum creatinine ≥2 mg/dl, serum β2-microglobulin ≥5500 mg/L, autologous stem cell transplant (SCT), and allogeneic SCT for analysis. Our results demonstrated that the non-prophylaxis group (HR: 2.37, 95% CI 1.57-3.57) and patients receiving autologous SCT (HR: 2.22, 95% CI 1.28-3.86) and allogeneic SCT (HR: 5.12, 95% CI 1.13-23.22) had higher risk of HZ infection. The difference in dosage and types of anti-HZ drugs showed similar protective effects. In patients who stopped anti-HZ prophylaxis before active cancer-related treatment, a higher risk of getting HZ infection compared to the corresponding group was also observed (adjusted HR 3.09, 95% CI 1.35-7.07, p = 0.008). CONCLUSIONS:We concluded that MM patients should receive HZ prophylaxis drugs while receiving active cancer-related treatment. Patients receiving SCT are also at high risk of getting HZ infection, even under prophylaxis.
10.1002/cam4.5215