A nationwide study on inpatient opportunistic infections in patients with chronic lymphocytic leukemia in the pre‐ibrutinib era

Steingrímsson, Vilhjálmur; Gíslason, Gauti Kjartan; Þorsteinsdóttir, Sigrún; Rögnvaldsson, Sæmundur; Gottfreðsson, Magnús; Aspelund, Thor; Turesson, Ingemar; Björkholm, Magnus; Landgren, Ola; Kristinsson, Sigurður Y.

doi:10.1111/ejh.13553

Cited by 6 publications

(10 citation statements)

References 48 publications

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“…1 Reactivation of latent varicella zoster virus (VZV) in the form of shingles, and postherpetic neuralgia is frequently associated with hematologic malignancies, including CLL. 2,3 The live zoster vaccine (ZVL; Zostavax) is no longer available in the United States and has been superseded by the recombinant, adjuvanted VZV vaccine (RZV) due to its improved efficacy and safety in immunocompromised patients. 4,5 RZV induces vaccine responses in cancer patients, 6 but there is a paucity of data guiding the best use of RZV for patients with CLL.…”

Section: Introductionmentioning

confidence: 99%

BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL

et al. 2022

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Vaccinations effectively prevent infections; however, patients with chronic lymphocytic leukemia (CLL) have reduced antibody responses following vaccinations. Combined humoral and cellular immune responses to novel adjuvanted vaccines are not well characterized in CLL. In an open-label, single-arm clinical trial, we measured the humoral and cellular immunogenicity of the recombinant zoster vaccine (RZV) in CLL patients who were treatment naïve (TN) or receiving Bruton tyrosine kinase inhibitor (BTKi) therapy. The primary endpoint was antibody response to RZV (≥4-fold increase in anti glycoprotein E [gE]). Cellular response of gE-specific CD4+ T cells was assessed by flow cytometry for upregulation of ≥ 2 effector molecules. The antibody response rate was significantly higher in the TN cohort (76.8% [95% confidence interval 65.7-87.8]) compared to patients receiving a BTKi (40.0% [26.4-53.6]; P = .0002). The cellular response rate was also significantly higher in the TN cohort (70.0% [57.3-82.7]) compared to the BTKi group (41.3% [27.1-55.5]; P = .0072). A concordant positive humoral and cellular immune response was observed in 69.1% [56.9-81.3] of subjects with a humoral response, whereas 39.0% [24.1-54.0] of subjects without a humoral response attained a cellular immune response (P = .0033). Antibody titers and T cell responses were not correlated with age, absolute B and T cell counts, or serum immunoglobulin levels (all P > 0.05). RZV induced both humoral and cellular immune responses in treated and untreated CLL patients, albeit with lower response rates in patients on BTKi therapy compared to TN patients. Registered at www.clinicaltrials.gov as #NCT03702231.

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Section: Introductionmentioning

confidence: 99%

BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL

et al. 2022

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“…In a Swedish nationwide analysis from 1994 to 2013 of inpatient opportunistic infectious complications in CLL patients, herpes zoster was second most common after pneumocystis jirovecii pneumonia. Incidence rates per 1000 patient-years were 2.94 for herpes zoster and 0.8 for HSV reactivations, compared to 0.26 and 0.04 respectively in the age-/sex-/residence-matched control group [ 97 ]. Only inpatients were included, thus patients with severe disease, which was also reflected by an early mortality rate of 15% (for herpes zoster) and 13% (for HSV reactivation) [ 97 ].…”

Section: Patient Groupsmentioning

confidence: 99%

“…Incidence rates per 1000 patient-years were 2.94 for herpes zoster and 0.8 for HSV reactivations, compared to 0.26 and 0.04 respectively in the age-/sex-/residence-matched control group [ 97 ]. Only inpatients were included, thus patients with severe disease, which was also reflected by an early mortality rate of 15% (for herpes zoster) and 13% (for HSV reactivation) [ 97 ]. A decreasing rate of herpes zoster cases during time course was possibly linked to increasing use of antiviral pharmacological prophylaxis.…”

Section: Patient Groupsmentioning

confidence: 99%

Management of herpesvirus reactivations in patients with solid tumours and hematologic malignancies: update of the Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) on herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus

et al. 2022

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Clinical reactivations of herpes simplex virus or varicella zoster virus occur frequently among patients with malignancies and manifest particularly as herpes simplex stomatitis in patients with acute leukaemia treated with intensive chemotherapy and as herpes zoster in patients with lymphoma or multiple myeloma. In recent years, knowledge on reactivation rates and clinical manifestations has increased for conventional chemotherapeutics as well as for many new antineoplastic agents. This guideline summarizes current evidence on herpesvirus reactivation in patients with solid tumours and hematological malignancies not undergoing allogeneic or autologous hematopoietic stem cell transplantation or other cellular therapy including diagnostic, prophylactic, and therapeutic aspects. Particularly, strategies of risk adapted pharmacological prophylaxis and vaccination are outlined for different patient groups. This guideline updates the guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO) from 2015 “Antiviral prophylaxis in patients with solid tumours and haematological malignancies” focusing on herpes simplex virus and varicella zoster virus.

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“…However, a unique set of toxicities has been reported for ibrutinib. Common adverse effects of ibrutinib observed in CLL and MCL patients include bleeding, atrial fibrillation, hypertension, neutropenia, arthralgias, myalgias, headache, diarrhea, nausea, fatigue, rash and infection (38,162,166,(173)(174)(175)(176)(177)(178)(179)(180). Based on the preliminary results posted at ClinicalTrials.gov, commonly observed adverse effects of ibrutinib in patients with other human diseases include fatigue, anemia, gastrointestinal disorders, thrombocytopenia, myalgia, arthralgia, bleeding and infection (Table 2).…”

Section: Major Toxicities and Potential Limitations Of Ibrutinib And Acalabrutinib In Therapeutic Usementioning

confidence: 99%

Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies

et al. 2021

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The BTK inhibitors ibrutinib and acalabrutinib are FDA-approved drugs for the treatment of B cell malignances. Both drugs have demonstrated clinical efficacy and safety profiles superior to chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia. Mounting preclinical and clinical evidence indicates that both ibrutinib and acalabrutinib are versatile and have direct effects on many immune cell subsets as well as other cell types beyond B cells. The versatility and immunomodulatory effects of both drugs have been exploited to expand their therapeutic potential in a wide variety of human diseases. Over 470 clinical trials are currently registered at ClinicalTrials.gov to test the efficacy of ibrutinib or acalabrutinib not only in almost every type of B cell malignancies, but also in hematological malignancies of myeloid cells and T cells, solid tumors, chronic graft versus host disease (cGHVD), autoimmune diseases, allergy and COVID-19 (http:www.clinicaltrials.gov). In this review, we present brief discussions of the clinical trials and relevant key preclinical evidence of ibrutinib and acalabrutinib as monotherapies or as part of combination therapies for the treatment of human diseases beyond B cell malignancies. Adding to the proven efficacy of ibrutinib for cGVHD, preliminary results of clinical trials have shown promising efficacy of ibrutinib or acalabrutinib for certain T cell malignancies, allergies and severe COVID-19. However, both BTK inhibitors have no or limited efficacy for refractory or recurrent solid tumors. These clinical data together with additional pending results from ongoing trials will provide valuable information to guide the design and improvement of future trials, including optimization of combination regimens and dosing sequences as well as better patient stratification and more efficient delivery strategies. Such information will further advance the precise implementation of BTK inhibitors into the clinical toolbox for the treatment of different human diseases.

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A nationwide study on inpatient opportunistic infections in patients with chronic lymphocytic leukemia in the pre‐ibrutinib era

Cited by 6 publications

References 48 publications

BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL

BTK inhibitors impair humoral and cellular responses to recombinant zoster vaccine in CLL

Clinical Trials of the BTK Inhibitors Ibrutinib and Acalabrutinib in Human Diseases Beyond B Cell Malignancies

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