pci-32765 and Exanthema

The scope of dermatologic adverse events to ibrutinib has not been systematically described. We sought to determine the incidence and severity of ibrutinib-associated dermatologic toxicities and provide management recommendations. We conducted a systematic literature search of clinical trials and cohorts investigating ibrutinib monotherapy for cancer or chronic graft-versus-host disease through June 2020. Thirty-two studies with 2258 patients were included. The incidence of all-grade toxicities included cutaneous bleeds (24.8%; 95%CI, 18.6-31.0%), mucocutaneous infections (4.9%; 95%CI, 2.9-7.0%), rash (10.8%; 95%CI. 6.1-15.5%), mucositis (6%; 95%CI, 3.6-8.5%), edema (15.9%; 95%CI, 11.1-20.6%), pruritus (4.0%; 95%CI, 0.0-7.9%), xerosis (9.2%; 95%CI, 5.5-13.0%), nail changes (17.8%; 95%CI, 4.1-31.5%), and hair changes (7.9%; 95%CI, 0.0-21.3%). The incidence of high-grade toxicities included mucocutaneous infection (1.3%; 95%CI, 0.5-2.2%), rash (0.1%; 95%CI, 0.0-0.2%), mucositis (0.1%; 95%CI, 0.0-0.3%), and edema (0.1%; 95%CI, 0.0-0.2%). It is imperative that clinicians familiarize themselves with ibrutinib-associated dermatologic toxicities to learn how to manage them, prevent discontinuation, and improve patient outcomes.

Topics: Adenine; Exanthema; Humans; Mucositis; Piperidines

Ibrutinib is a transformative therapy for high-risk and relapsed refractory chronic lymphocytic leukemia (CLL) patients. In clinical trials in relatively healthy younger patients, ibrutinib has been well tolerated. As its use has become more widespread in the community, however, its full adverse event profile has emerged and proven more challenging than was initially anticipated. Reports of community-based use have estimated discontinuation rates as high as 40% in the first year of therapy. This article therefore reviews my approach to the evaluation and management of a CLL patient starting on ibrutinib, with the goal of minimizing and managing toxicity to maintain patients on ibrutinib. Key topics discussed include bleeding risk; cardiac complications, particularly atrial fibrillation; drug interactions; and infections.

Topics: Adenine; Aged; Aged, 80 and over; Atrial Fibrillation; Autoimmunity; Communicable Diseases; Disease Management; Drug Interactions; Exanthema; Female; Hemorrhage; Humans; Hypertension; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines

Ibrutinib is indicated in Europe for the treatment of several B-cell malignancies, including chronic lymphocytic leukaemia (CLL). However, despite the high efficacy and favourable toxicity profile of ibrutinib, recent data suggest that it is not always administered optimally in clinical practice, with an increased tendency for dose reduction and a higher frequency of discontinuation. An expert panel of European haematologists was convened to identify practical issues pertinent to physicians involved in the therapeutic management of ibrutinib-treated CLL patients and here we outline the findings. Practical management recommendations are given for treating patients with ibrutinib and clinical considerations for the management of adverse events (AEs) that can be associated with ibrutinib treatment are addressed. This article highlights that patients should be monitored for treatment emergent adverse events, most of which are mild, transient and generally occur early in therapy and that, even with more challenging AEs, patients can often be maintained on therapy with minimal disruption through careful management. The necessity to use the correct ibrutinib dose, along with increased awareness, vigilance, mitigation and management of AEs, are all recommended to maximise outcomes for CLL patients treated with ibrutinib.

Topics: Adenine; Anticoagulants; Antineoplastic Agents; Arthralgia; Atrial Fibrillation; Diabetes Mellitus, Type 1; Diarrhea; Drug Eruptions; Drug Interactions; Exanthema; Fatigue; Hemorrhage; Humans; Hypertension; Infections; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphocytosis; Medication Adherence; Myalgia; Piperidines; Platelet Aggregation Inhibitors; Pyrazoles; Pyrimidines; Treatment Outcome

Ibrutinib is an oral inhibitor of Bruton tyrosine kinase that is approved by the United States Food and Drug Administration for several lymphoproliferative disorders and chronic graft-versus-host disease.. To characterize cutaneous eruptions arising from ibrutinib and highlight overlap with epidermal growth factor receptor (EGFR) inhibitor-induced dermatologic adverse events.. Single-center retrospective cohort of patients referred to the Skin Toxicities Program for treatment of cutaneous eruptions while taking ibrutinib.. Among 19 patients, cutaneous eruptions manifested as facial-predominant papulopustular eruptions, petechiae, or ecchymoses, photosensitivity, panniculitis, xerosis, and clinical staphylococcal overgrowth. Most patients were able to continue ibrutinib therapy with focused treatment of their cutaneous toxicities.. This study represents cases at a single tertiary care center and is limited to patients referred for toxicity.. With the exception of petechiae, the cutaneous toxicities of ibrutinib overlap with those associated with selective EGFR inhibitors. We observed that these reactions can be successfully managed using approaches for EGFR inhibitor-induced cutaneous adverse events.

Topics: Drug Eruptions; ErbB Receptors; Exanthema; Humans; Protein Kinase Inhibitors; Retrospective Studies

Schnitzler syndrome is a rare adult-onset acquired autoinflammatory disorder typically characterized by chronic urticarial rash and immunoglobulin M (IgM) (rarely IgG) monoclonal gammopathy. Its clinical symptoms usually respond well to interleukin-1 blockade therapy, which, however, does not impact the underlying monoclonal gammopathy. Herein, we described a female patient who presented with urticarial rash, recurrent fevers, and fatigue for 7 years. Laboratory investigations revealed IgMκ monoclonal protein and

Topics: Adenine; Adult; Antibodies, Monoclonal; Exanthema; Female; Humans; Piperidines; Schnitzler Syndrome; Urticaria

Topics: Adenine; Aged; Biopsy; Exanthema; Humans; Immunohistochemistry; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Protein Kinase Inhibitors; Severity of Illness Index; Skin

Topics: Adenine; Aged, 80 and over; Exanthema; Histocytochemistry; Humans; Male; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Schnitzler Syndrome; Skin; Treatment Outcome

Topics: Adenine; Antineoplastic Agents; Biopsy; Disease Management; Exanthema; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Piperidines; Protein Kinase Inhibitors; Pyrazoles; Pyrimidines; Severity of Illness Index; Symptom Assessment

Topics: Adenine; Aged; Allopurinol; Antimetabolites; Antineoplastic Agents; Chromosome Deletion; Chromosomes, Human, Pair 17; Exanthema; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Piperidines; Pyrazoles; Pyrimidines; Smith-Magenis Syndrome