acyclovir and Multiple-Myeloma

Bortezomib is proteasome inhibitor used in multiple myeloma treatment. The reactivation of herpes simplex virus (HSV) and varicella-zoster virus (VZV) during bortezomib-based therapy is a well-known adverse event. Antiviral prophylaxis is mandatory. Nevertheless, reports of herpesviral encephalitis are scarce.. A 57-year-old multiple myeloma patient who during CyBorD protocol (Bortezomib, cyclophosphamide, and dexamethasone), after a transient suspension of antiviral prophylaxis presented progressive headaches unresponsive to conventional analgesics, asthenia, fever, episodic visual hallucinations, and vesicular lesions in the right supraorbital and frontal region. Herpetic encephalitis was diagnosed after detecting herpes zoster in cerebrospinal fluid.. The patient was treated with acyclovir 500mg every 6 hours for 21 days, and subsequent valacyclovir prophylaxis achieving an excellent clinical evolution. Anti-myeloma treatment was changed to lenalidomide and dexamethasone achieving a durable complete response. Herpesviral encephalitis is a rare but severe complication associated with the use of Bortezomib, especially when patients did not receive acyclovir prophylaxis. However, a rapid detection based on the clinical suspicion, and the prompt start of treatment, may lead to overcome this adverse event.

Topics: Acyclovir; Amyloidosis; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Dexamethasone; Encephalitis, Herpes Simplex; Herpesvirus 3, Human; Humans; Middle Aged; Multiple Myeloma; Pyrazines

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.. 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).. 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.. Zoster prophylaxis with low-dose acyclovir over 12 months after ASCT is effective and well tolerated.

Topics: Acyclovir; Hematopoietic Stem Cell Transplantation; Herpes Zoster; Herpesvirus 3, Human; Humans; Lymphoma; Multiple Myeloma; Retrospective Studies; Stem Cell Transplantation; Transplantation, Autologous

Topics: Acyclovir; Diagnosis, Differential; Dyspnea; Herpes Simplex; Herpesvirus 1, Human; Humans; Immunosuppressive Agents; Laryngitis; Laryngostenosis; Larynx; Male; Middle Aged; Multiple Myeloma; Tracheotomy; Treatment Outcome; Valacyclovir

Topics: Acyclovir; Aged; Antineoplastic Agents; Antiviral Agents; Bortezomib; Cohort Studies; Female; Hematopoietic Stem Cell Transplantation; Herpesvirus 3, Human; Humans; Male; Middle Aged; Multiple Myeloma; Outcome Assessment, Health Care; Time Factors; Transplantation, Autologous; Valacyclovir; Valine; Varicella Zoster Virus Infection

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.

Topics: Acyclovir; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibiotic Prophylaxis; Antiviral Agents; Encephalitis, Varicella Zoster; Female; Germany; Herpes Simplex; Herpes Zoster; Herpesvirus 3, Human; Humans; Immunocompromised Host; Incidence; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Polyradiculopathy; Risk Factors; Simplexvirus; Thalidomide

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Boronic Acids; Bortezomib; Dose-Response Relationship, Drug; Female; Herpes Zoster; Humans; Male; Middle Aged; Multiple Myeloma; Pyrazines; Retrospective Studies

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.. 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.. 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.. 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.

Topics: Acyclovir; Aged; Aged, 80 and over; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Multiple Myeloma; Pyrazines; Retrospective Studies; Valacyclovir; Valine; Virus Activation

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.. 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.. 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.. 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.

Topics: Acyclovir; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Multiple Myeloma; Neoplasm Staging; Pyrazines; Retrospective Studies; Salvage Therapy; Survival Rate; Treatment Outcome

Herpes zoster is the most common infection in patients treated with bortezomib-containing regimens for multiple myeloma. Some clinical trials have reported on the use of acyclovir prophylaxis to decrease the incidence of herpes zoster. However, the appropriate acyclovir dose and duration of prophylaxis remain unclear. The primary objective of this study was to evaluate the efficacy of continuous oral 200 mg/day acyclovir prophylaxis and the secondary objective was to determine the risk factors for developing herpes zoster.. We collected medical information from consecutive patients who received bortezomib with or without acyclovir prophylaxis for relapsed or refractory multiple myeloma at our hospital and retrospectively analyzed the efficacy of acyclovir prophylaxis and the parameters for predicting the risk factors for developing herpes zoster. The definition of acyclovir prophylaxis was oral continuous administration of 200 mg of once daily, without cessation, during the entire period of bortezomib treatment.. Six of the 33 patients in the study developed herpes zoster during bortezomib treatment. No varicella-zoster virus reactivation was observed in the 19 patients in the acyclovir prophylaxis group. The incidence of herpes zoster was significantly higher in the group that did not receive acyclovir prophylaxis (43%, 6 of 14 patients) than in the group that did (0%, 0 of 19; P = 0.003). The predictive factors for varicella-zoster virus reactivation were male sex (P = 0.035) and the use of acyclovir (P = 0.003).. Continuous prophylaxis by oral 200 mg/day acyclovir in multiple myeloma patients receiving bortezomib treatment is effective and sufficient in preventing herpes zoster.

Topics: Acyclovir; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Boronic Acids; Bortezomib; Drug Administration Schedule; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Multiple Myeloma; Pyrazines; Retrospective Studies; Risk Factors; Secondary Prevention; Treatment Outcome

Retrospective analysis of two recent multiple myeloma (MM) clinical trials suggested that the use of bortezomib may be associated with an increased incidence of herpes zoster infections. Therefore, prophylactic use of antivirals has been advocated by some authors. This article explores the potential risks and pitfalls linked to routine acyclovir prophylaxis in bortezomib-treated MM.. use of antivirals can be associated with important nephro- and neurotoxicity. The nephrotoxicity induced by MM itself and its supportive therapies, superimposed to aging and inherent immunosuppression in myeloma, makes the development of renal impairment even more likely. On the other hand, sensory neuropathy is known to occur both during myeloma progression and in the setting of bortezomib therapy. Furthermore, preexisting nephropathy in MM patients can contribute to the occurrence of serious neurologic toxicity with acyclovir.. long-term acyclovir prophylaxis in MM patients treated with bortezomib may cause severe renal and neurological toxicity. Prevention of these complications can be achieved through either withholding of the antivirals or a very close monitoring of both neurologic status and renal function in this patient population. This highlights the importance of both clinician's and pharmacist's involvement in optimization of myeloma patient care.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Drug Monitoring; Herpes Zoster; Herpesvirus 3, Human; Humans; Incidence; Multiple Myeloma; Neurotoxicity Syndromes; Pyrazines; Renal Insufficiency; Virus Activation

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

Topics: Acyclovir; Boronic Acids; Bortezomib; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Multiple Myeloma; Pyrazines; T-Lymphocytes

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Cyclosporine; Dexamethasone; Drug Hypersensitivity; Exanthema Subitum; Herpesvirus 3, Human; Herpesvirus 6, Human; Humans; Male; Melphalan; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Prednisone; Pyrazines; Syndrome; Virus Activation

Humoral-mediated as well as cell-mediated immunity is compromised in myeloma patients receiving treatment. Immunocompromised patients are at risk of developing herpes zoster. There is evidence from clinical trials that bortezomib therapy is associated with a significant risk of herpes zoster. It is the authors' clinical policy to administer long-term acyclovir prophylactically to all symptomatic myeloma patients.. A retrospective review of the records of 125 myeloma patients who were treated with bortezomib and who also received routine acyclovir prophylaxis at the dose of 400 mg daily in >80% of patients was undertaken. Alternatives, used in <20% of patients, were 200 mg of acyclovir, 250/500 mg of valacyclovir, or 500 mg of famciclovir administered daily. This was accompanied by patient education regarding the importance of compliance with these prophylactic medications.. The duration of bortezomib therapy was 1 to 164 weeks (median, 16 weeks). The total duration of exposure to bortezomib was 4150 weeks (80 patient-years). Except for the occasional missed dose, the self-reported compliance with antiviral prophylaxis was 100%. Not a single episode of herpes zoster was reported during this period. No adverse effects were noted that could be definitely attributed to acyclovir, valacyclovir, or famciclovir.. Daily acyclovir (or a suitable alternative) appears to be effective at preventing herpes zoster virus in patients with myeloma who are receiving bortezomib, with or without corticosteroids.

Topics: Acyclovir; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Herpes Zoster; Herpesvirus 3, Human; Humans; Multiple Myeloma; Pyrazines; Retrospective Studies; Virus Activation

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.. 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.. 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.. 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.

Topics: Acyclovir; Aged; Aged, 80 and over; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Female; Herpes Zoster; Herpesvirus 3, Human; Humans; Male; Middle Aged; Multiple Myeloma; Prospective Studies; Pyrazines; Virus Activation

A novel molecular targeting drug, a proteasome inhibitor, bortezomib (Bor), has been reported to be highly effective for relapsed/refractory, as well as for newly diagnosed multiple myeloma, but is also associated with a high frequency of herpes zoster (HZ) infection (13%). We conducted a retrospective survey on HZ infection (profile) after Bor therapy in our hospital. Six of 30 patients developed HZ infection during bortezomib-dexamethasone treatment (BD therapy). Age, performance status, and stem cell transplantation were not related risk factors for HZ infection. HZ developed when acyclovir (ACV) was not administrated to all six cases. Continuous administration of ACV decreased the incidence of HZ infection. Based on these results, we started an anti- HZ prophylaxis program using ACV for all patients receiving BD therapy. Further study is warranted to establish the optimal dose and duration of ACV for appropriate prophylaxis of HZ infection.

Topics: Acyclovir; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Antiviral Agents; Boronic Acids; Bortezomib; Dexamethasone; Drug Administration Schedule; Female; Herpes Zoster; Humans; Male; Middle Aged; Multiple Myeloma; Protease Inhibitors; Pyrazines; Retrospective Studies

Topics: Acyclovir; Anti-Inflammatory Agents; Antineoplastic Agents; Antiviral Agents; Boronic Acids; Bortezomib; Dexamethasone; Exanthema; Herpes Zoster; Humans; Male; Middle Aged; Multiple Myeloma; Pyrazines; Skin; Treatment Outcome

Topics: Acyclovir; alpha 1-Antitrypsin Deficiency; Drug Interactions; Drug Resistance, Microbial; Gene Expression; Heparin; HIV Infections; Humans; Multiple Myeloma; National Institutes of Health (U.S.); Receptors, HIV; Registries; Simplexvirus; Tissue Plasminogen Activator; United States; Virus Replication