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The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell-engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

Immune checkpoint inhibitors (ICI) represent a breakthrough in cancer therapy. They are effective in various tumor entities and can be used in more and more treatment settings. This leads to an increase in the number and complexity of cases with immune-related adverse events (irAE). The most common irAE are cutaneous, gastrointestinal and endocrine side effects, whereas less common irAE include pneumonitis, nephritis, myocarditis or neurological reactions. IrAE can usually be successfully treated, mainly with corticosteroids or other immunosuppressants, but they can also result in long-term sequelae or death. The optimal management of patients with steroid-refractory or steroid-dependent side effects still remains unclear. Broad awareness of these irAE across specialties is therefore of crucial importance to ensure early diagnosis and to improve irAE management., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Objectives: The use of immune checkpoint inhibitors (ICIs) as anticancer therapy across a variety of malignancies has led to durable efficacy in a subset of patients. However, associated side effects denoted immune-related adverse events (irAEs) have emerged and can result in substantial morbidity and mortality. Particularly early in the experience of using these agents, a lack of standardized education regarding irAEs among patients and clinical providers may have contributed to poor outcomes. Optimal management of these emerging toxicities depends on a coordinated institutional approach. We hypothesized that centralized educational programs and electronic health record (EHR)-based interventions, targeted both toward ICI-treated patients as well as patient-interfacing providers, would improve patient outcomes., Methods: We created a multidisciplinary team of clinicians and associated staff to direct a coordinated approach to the education and management of patients receiving ICIs across our institution. A 3-tiered approach was designed: patient-centered, internally centered, and externally centered. Multimedia educational products were produced for patients to improve knowledge and awareness of ICIs and associated irAEs. An EHR-based banner was deployed to improve identification of patients receiving ICIs across disciplines. Tailored educational seminars were provided to clinicians who interact with ICI-treated patients at all levels. Educational seminars were also offered to local physicians and institutions. We assessed patient uptake of educational products and surrogate patient outcomes to measure the potential impact of our interventions., Results: Fox Chase Cancer Center (FCCC)-specific ICI identification cards were created and distributed to patients. By the end of the investigational period, 98.6% of ICI-treated patients reported receiving a card. An ICI-focused on-line portal was created accessible only to ICI-treated patients, with 9.4% of these patients accessing the portal in the first 6 months without marketing promotion. Deidentified surrogate clinical endpoints of corticosteroid use, direct referral unit (DRU) visits, and hospital admissions all improved during the study period., Conclusions: Institutionally directed educational initiatives are feasible at a free-standing academic cancer center and may lead to improved outcomes in patients developing irAEs from ICIs. More granular patient-specific data and studies at other types of institutions are necessary to determine the applicability of similar approaches on a broader scale., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Immune checkpoint inhibitors (ICIs) have emerged as crucial therapeutic agents for various malignancies by activating the host immune system against tumor cells. However, many different types of skin adverse reactions may occur during its use, including eruption, pruritus, blistering, hypopigmentation, alopecia, and even severe cases, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). These cutaneous immune-related adverse events (cirAEs) had a high incidence, which seriously affected patients' quality of life and antitumor treatment decisions. Some severe cutaneous adverse reactions (SCARs) even endanger patients' lives. Therefore, the Chinese Society of Dermatology, the Chinese Dermatologist Association of the Chinese Medical Doctor Association, the Dermatology Division of the Chinese Geriatrics Society, and other relevant experts jointly discussed and formulated the 'Chinese Expert Consensus on the Diagnosis and Treatment of Immune Checkpoint Inhibitor-Related Cutaneous Adverse Reactions'. This consensus covers the name, epidemiology, pathogenesis, clinical features, classification and grading of cirAEs, principles of management and the re-initiation of ICIs. It aims to provide a more scientific and authoritative reference for the diagnosis and treatment of cirAEs in China in the future.

Immune checkpoint inhibitors (ICIs) have transformed the treatment paradigm for many cancer types. The clinical use of ICIs is increasing rapidly, including in combinations associated with increased risk of toxicities, termed "immune-related adverse events" (irAEs). Therefore, MD Anderson Cancer Center (MDACC) in Houston, Texas has proactively responded by developing a priority endeavor known as the Immuno-Oncology Toxicity (IOTOX) initiative. This strategic initiative aims to facilitate the seamless integration of key domains: (1) standardized clinical practice and innovative decision toolsets; (2) patient and provider education; and (3) a comprehensive clinical and translational research platform. The ultimate goal of this initiative is to develop and disseminate clinical best practices and biologic insights into irAEs to improve outcomes of patients with irAEs at MDACC and in the wider oncology community.

Background: Immunotherapy has reshaped the prognoses for many cancers and is increasingly used in both metastatic and adjuvant settings. There is a high prevalence of immunotherapy side effects, or immune-related adverse events (irAEs), which can affect any organ. Some irAEs can cause permanent or prolonged morbidity and, in rare cases, may be fatal. irAEs can present with mild, non-specific symptoms, resulting in delays to identification and management., Objective: We aim to provide a general overview of immunotherapy and irAEs, highlighting common clinical scenarios and general principles of management., Discussion: Cancer immunotherapy toxicity is an important clinical problem that is increasingly relevant to general practice, where patients with adverse events may first present. Early diagnosis and timely intervention are important in limiting the severity and morbidity of these toxicities. The management of irAEs should follow treatment guidelines, in consultation with patients' treating oncology teams.

Extravasation is the leakage of intravenous solutions into surrounding tissues, which can be influenced by drug properties, infusion techniques, and patient-related risk factors. Although peripheral administration of vesicants may increase the risk of extravasation injuries, the time and resources required for central venous catheter placement may delay administration of time-sensitive therapies. Recent literature gathered from the growing use of peripheral vasopressors and hypertonic sodium suggests low risk of harm for initiating these emergent therapies peripherally, which may prevent delays and improve patient outcomes. Physiochemical causes of tissue injury include vasoconstriction, pH-mediated, osmolar-mediated, and cytotoxic mechanisms of extravasation injuries. Acidic agents, such as promethazine, amiodarone, and vancomycin, may cause edema, sloughing, and necrosis secondary to cellular desiccation. Alternatively, basic agents, such as phenytoin and acyclovir, may be more caustic due to deeper tissue penetration of the dissociated hydroxide ions. Osmotically active agents cause cellular damage as a result of osmotic shifts across cellular membranes in addition to agent-specific toxicities, such as calcium-induced vasoconstriction and calcifications or arginine-induced leakage of potassium causing apoptosis. A new category has been proposed to identify absorption-refractory mechanisms of injury in which agents such as propofol and lipids may persist in the extravasated space and cause necrosis or compartment syndrome. Pharmacological antidotes may be useful in select extravasations but requires prompt recognition and frequently complex administration strategies. Historically, intradermal phentolamine has been the preferred agent for vasopressor extravasations, but frequent supply shortages have led to the emergence of terbutaline, a β 2 -agonist, as an acceptable alternative treatment option. For hyperosmolar and pH-related mechanisms of injuries, hyaluronidase is most commonly used to facilitate absorption and dispersion of injected agents. However, extravasation management is largely supportive and requires a protocolized multidisciplinary approach for early detection, treatment, and timely surgical referral when required to minimize adverse events., (© 2023 Pharmacotherapy Publications, Inc.)

Parkinson's disease (PD) is a neurodegenerative disease with a heavy burden on patients, families, and society. Deep brain stimulation (DBS) can improve the symptoms of PD patients for whom medication is insufficient. However, current open-loop uninterrupted conventional DBS (cDBS) has inherent limitations, such as adverse effects, rapid battery consumption, and a need for frequent parameter adjustment. To overcome these shortcomings, adaptive DBS (aDBS) was proposed to provide responsive optimized stimulation for PD. This topic has attracted scientific interest, and a growing body of preclinical and clinical evidence has shown its benefits. However, both achievements and challenges have emerged in this novel field. To date, only limited reviews comprehensively analyzed the full framework and procedures for aDBS implementation. Herein, we review current preclinical and clinical data on aDBS for PD to discuss the full procedures for its achievement and to provide future perspectives on this treatment.

Objectives: Myelofibrosis is a rare bone marrow disorder associated with a high symptom burden, poor prognosis, and shortened survival. While allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for myelofibrosis, the only approved and reimbursed pharmacotherapy for non-HSCT candidates in Belgium is ruxolitinib., Methods: These updated recommendations are based on a consensus reached during two meetings and provide guidance for ruxolitinib administration in myelofibrosis patients considering the particularities of Belgian reimbursement criteria., Results and Discussion: In Belgium, ruxolitinib is indicated and reimbursed for transplant-ineligible myelofibrosis patients from intermediate-2- and high-risk groups and from the intermediate-1-risk group with splenomegaly. Our recommendation is to also make ruxolitinib available in the pre-transplant setting for myelofibrosis patients with splenomegaly or heavy symptom burden. Before ruxolitinib initiation, complete blood cell counts are recommended, and the decision on the optimal dosage should be based on platelet count and clinical parameters. In anemic patients, we recommend starting doses of ruxolitinib of 10 mg twice daily for 12 weeks and we propose the use of erythropoiesis-stimulating agents in patients with endogenous erythropoietin levels ≤500 mU/mL. Increased vigilance for opportunistic infections and second primary malignancies is needed in ruxolitinib-treated myelofibrosis patients. Ruxolitinib treatment should be continued as long as there is clinical benefit (reduced splenomegaly or symptoms), and we recommend progressive dose tapering when stopping ruxolitinib., Conclusion: Based on new data and clinical experience, the panel of experts discussed ruxolitinib treatment in Belgian myelofibrosis patients with a focus on dose optimization/monitoring, adverse events, and interruption/rechallenge management.

Aim: Unexplained infertility is a major burden for couples who want to have children. Lymphocyte immunotherapy (LIT) could be a therapeutic help for these couples. Although LIT has been carried out for decades, the data on the success of therapy are still controversial and there is hardly information on possible adverse drug reactions., Methods: In this study, we used a questionnaire to determine the frequency of local and systemic adverse drug reactions in our patients who were treated with LIT between 2017 and 2020 (n = 302). In addition, we asked about pregnancies and/or live births after LIT in a 2-year follow-up (n = 140)., Results: Most of the patients reported the occurrence of mild local adverse drug reactions in a period of less than 4 weeks: Over 75% reported moderate erythema, itching or swelling, over 10% erythema, itching or swelling as more pronounced adverse drug reaction. Blistering was specified in 10% of the cases. Serious adverse drug reactions or adverse events were not described. In the follow-up, 69% of our patients stated a pregnancy after LIT, and 50% a life birth., Conclusions: Overall, LIT represents a well-tolerated therapy for couples with unexplained infertility, however, more evidence is needed on the benefits., (© 2022 The Authors. Journal of Obstetrics and Gynaecology Research published by John Wiley & Sons Australia, Ltd on behalf of Japan Society of Obstetrics and Gynecology.)

Immune-oncologic (IO) therapy has revolutionized the treatment and management of oncologic disease. Immunotherapy functions by enhancing the host immune-systems ability to endogenously clear malignant cells, however, this activation can also lead to immune-mediated damage to healthy native tissues. These side effects are known as immune-related adverse events or irAEs and can even present with phenotypes similar to autoimmune diseases. IrAEs are the major consequence of checkpoint inhibitors and can have a significant impact on a patient's cancer treatment and long-term quality of life. The management of these irAEs follows a similar approach to autoimmune diseases. More specifically, the management is akin to that of autoimmune disease exacerbations. While there is an array of immune-suppressing agents that can be used, steroids, immunomodulators and IO discontinuation are cornerstones of irAE management. The exact approach and dosing are based on the severity and subtype of irAE presented. Within recent years, there has been a push to better prevent and manage irAEs when they arise. There has been an additional effort to increase the number of steroid-sparing agents available for irAE treatment given the consequences of long-term steroid therapy as well as patient contraindications to steroids. The goals of this review are to summarize irAE management, highlight significant advances made in recent years and emphasize the future directions that will optimize the use of IO therapy in oncology., Competing Interests: MB has acted as a paid consultant for and/or as a member of the advisory boards of Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Genomic Health, Nektar, and Sanofi and has received grants to his institution from Xencor, Bayer, Bristol-Myers Squibb, Genentech/Roche, Seattle Genetics, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Peleton Therapeutics, and Pfizer for work performed as outside of the current study. BN has acted as a paid member of the advisory board of Exelixis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Olsen, Zhuang, Caulfield, Martini, Brown, Carthon, Kucuk, Harris, Bilen and Nazha.)

Lenvatinib is an oral multikinase inhibitor approved for use as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, like other agents in this drug class, lenvatinib is associated with clinically important adverse events (AEs) that could adversely affect patient outcomes. Hypertension, diarrhea, decreased appetite/weight, hand-foot skin reaction, and proteinuria are among the most common AEs associated with lenvatinib therapy. This article provides strategies for the effective management of lenvatinib-associated AEs based on the expert opinion of authors and currently available literature. Due to the high risk of AEs in patients receiving lenvatinib, prophylactic measures and regular monitoring for AEs are recommended. Lenvatinib dose interruption, adjustment, or discontinuation of treatment may be required for patients who develop AEs. For grade 1 or 2 AEs, dose interruption is generally not required. For persistent or intolerable grade 2 or 3 AEs, lenvatinib treatment should be interrupted until symptoms improve/resolve to grade 0-1 or baseline levels. Thereafter, treatment should be resumed at the same or a lower dose. Disease progression may occur in patients who do not initially respond to treatment or receive a suboptimal lenvatinib dose following dose reduction, resulting in lack of efficacy. Therefore, to derive maximum treatment benefit and ensure long-term disease control, lenvatinib should be maintained at the highest possible dose when managing AEs. To conclude, lenvatinib-associated AEs can be managed with prophylactic measures, regular monitoring and symptomatic management, which can ensure continued treatment and maximum survival benefit in patients with advanced HCC receiving first-line lenvatinib therapy., (© 2021 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: To design a physician and patient derived tool, the Adverse Event Unit (AEU), akin to currency (e.g. U.S. Dollar), to improve AE burden measurement independent of any particular disease or medication class., Patients/methods: A Research Electronic Data Capture (REDCap) online survey was administered to United States physicians with board certification or board eligibility in general neurology, subspecialty neurology, primary care internal medicine or family medicine, subspecialty internal medicine, general pediatrics, and subspecialty pediatrics. Physicians assigned value to 73 AE categories chosen from the Common Terminology Criteria of Adverse Events (CTCAE) relevant to neurologic disorder treatments. An online forced choice survey was administered to non-physician, potential patients, through Amazon Mechanical Turk (MTurK) to weight the severity of the same AE categories. Physician and non-physician data was combined to assign value to the AEU. Surveys completed between 1/2017 and 3/2019., Results: 363 physicians rated the 73 AE categories derived from CTCAE. 660 non-physicians completed forced choice experiments comparing AEs. The AEU provides 0-10, weighted values for the AE categories studied that differ from the ordinal 1-4 CTCAE scale. For example, CTCAE severe diabetes (category 4) is assigned an AEU score of 9. Although non-physician input changed physician assigned AEU values, there was general agreement among physicians and non-physicians about severity of AEs., Conclusion: The AEU has promise to be a useful, practical tool to add precision to AE burden measurement in the clinic and in comparative efficacy research with neurology patients. AEU utility will be assessed in planned comparative efficacy clinical trials., Competing Interests: The authors have read the journal’s policy and have the following competing interests: MH has consulted for Alexion, Argenx, CSL Behring, and Octapharma, and EDS serves on the speaker bureau for both Alexion and CSL Behring. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aim: To understand the preferences of US patients and oncologists for PARP inhibitors as second-line maintenance (2LM) for epithelial ovarian cancer. Methods: A discrete choice experiment was conducted to assess the preferences of treatment attributes. Results: The most valued attributes were risk of grade 3/4 adverse events (AEs; patients, n = 204) and progression-free survival (PFS; oncologists, n = 151). To accept a 37% increased risk of grade 3/4 AEs, PFS would need to increase by 27.9 months (patients) and 6.3 months (oncologists). The least valued attributes were dosing form/frequency (patients) and grade 3/4 anemia risk (oncologists). Conclusion: Patients' and oncologists' willingness to make benefit-risk trade-offs in the 2LM setting suggests that the PFS gains observed in selected studies of poly (ADP-ribose) polymerase inhibitors in BRCA-mutated disease are worth the toxicity risk.

Purpose: To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events (irAEs) in patients treated with chimeric antigen receptor (CAR) T-cell therapy., Methods: A multidisciplinary panel of medical oncology, neurology, hematology, emergency medicine, nursing, trialists, and advocacy experts was convened to develop the guideline. Guideline development involved a systematic literature review and an informal consensus process. The systematic review focused on evidence published from 2017 to 2021., Results: The systematic review identified 35 eligible publications. Because of the paucity of high-quality evidence, recommendations are based on expert consensus., Recommendations: The multidisciplinary team issued recommendations to aid in the recognition, workup, evaluation, and management of the most common CAR T-cell-related toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, B-cell aplasia, cytopenias, and infections. Management of short-term toxicities associated with CAR T cells begins with supportive care for most patients, but may require pharmacologic interventions for those without adequate response. Management of patients with prolonged or severe CAR T-cell-associated cytokine release syndrome includes treatment with tocilizumab with or without a corticosteroid. On the basis of the potential for rapid decline, patients with moderate to severe immune effector cell-associated neurotoxicity syndrome should be managed with corticosteroids and supportive care.Additional information is available at www.asco.org/supportive-care-guidelines., Competing Interests: Reprint Requests: Bianca D. SantomassoConsulting or Advisory Role: Celgene, Janssen, Legend Biotech, Incyte, In8BioResearch Funding: ADC Therapeutics (Inst) Loretta J. NastoupilHonoraria: Celgene, Gilead Sciences, Novartis, Bayer, Janssen Oncology, Pfizer, Gamida Cell, TG Therapeutics, Bristol Myers Squibb, ADC Therapeutics, Morphosys, Epizyme, GenmabResearch Funding: TG Therapeutics, Janssen Biotech, Celgene, Genentech/Roche, LAM Therapeutics, Epizyme, Novartis, IgM Biosciences, Caribou Biosciences, Gilead Sciences, Allogene Therapeutics, Takeda Sherry AdkinsConsulting or Advisory Role: CelgeneTravel, Accommodations, Expenses: Celgene Bryan J. SchneiderResearch Funding: Merck Milan AnadkatStock and Other Ownership Interests: Anthem, Humana, Perrigo, Walgreens Boots Alliance, Abbott Laboratories, Merck, AbbVie, Amgen, Bristol Myers Squibb, Celgene, CVS Health, Gilead Sciences, Incyte, Johnson & Johnson, Lilly, Medtronic, Mylan, Pfizer, Procter & Gamble, United Health Group, Regeneron, Roche, Moderna Therapeutics, Dexcom, Quest DiagnosticsHonoraria: Adgero Biopharmaceuticals, Boehringer Ingelheim, Novocure, AbbVie, UCB, InnovadermConsulting or Advisory Role: Adgero Biopharmaceuticals, Boehringer Ingelheim, Novocure, Kintara TherapeuticsResearch Funding: AnaptysBio, Boehringer Ingelheim, Biogen, InflaRx, Lutris, Novartis, OnQuality Pharmaceuticals, Veloce Pharmaceuticals, XBiotech, UCB, AbbVie, Lilly Michael B. AtkinsStock and Other Ownership Interests: Werewolf Pharma, PyxisConsulting or Advisory Role: Genentech, Novartis, Bristol Myers Squibb, Merck, Exelixis, Eisai, Agenus, Arrowhead Pharmaceuticals, Werewolf Pharma, Surface Oncology, Iovance Biotherapeutics, Pyxis, Pneuma Respiratory, Leads Biolabs, Fathom Biotechnology, Aveo, Cota Healthcare, Neoleukin Therapeutics, Adagene, Idera, Ellipses Pharma, AstraZeneca, PACT Pharma, Seattle Genetics, Pfizer, Scholar Rock, Asher Bio, Calithera Biosciences, Takeda, SanofiResearch Funding: Bristol Myers Squibb Kelly J. BrassilEmployment: Pack HealthHonoraria: Oncology Nursing Society, WebMD, M Consulting, i3 HealthResearch Funding: AbbVie, Daiichi Sankyo, Astellas Pharma, Genentech, Sanofi, GlaxoSmithKlineTravel, Accommodations, Expenses: Pack Health Jeffrey M. CaterinoStock and Other Ownership Interests: Motive Medical IntelligenceConsulting or Advisory Role: Wellstat TherapeuticsResearch Funding: Stago, Entegrion, JDP Therapeutics, AstraZeneca Ian ChauHonoraria: Lilly, Eisai, ServierConsulting or Advisory Role: Lilly, Bristol Myers Squibb, MSD Oncology, Merck Serono, Roche/Genentech, AstraZeneca, Pierre Fabre, Boehringer Ingelheim, Incyte, OncXerna Therapeutics, Astellas Pharma, GlaxoSmithKline, Eisai, SotioResearch Funding: Janssen-Cilag, LillyTravel, Accommodations, Expenses: MSD, Merck Serono, Lilly, Bristol Myers Squibb, Eisai Marianne J. DaviesSpeakers' Bureau: AstraZeneca, Genentech/Roche, Merck, Bristol Myers Squibb Marc S. ErnstoffStock and Other Ownership Interests: GE Healthcare, Bristol Myers SquibbResearch Funding: Alkermes, EMD SeronoTravel, Accommodations, Expenses: ImmuNext, AlkermesOther Relationship: Bristol Myers Squibb Leslie FecherConsulting or Advisory Role: Via Oncology, Hoosier Cancer Research Network, ElsevierResearch Funding: Merck, Incyte, Bristol Myers Squibb, Pfizer/EMD Serono, Array BioPharma, Kartos TherapeuticsOther Relationship: Array BioPharmaUncompensated Relationships: NCCN, American Association of Clinical Endocrinology, ASCO Pauline FunchainConsulting or Advisory Role: EisaiResearch Funding: Pfizer, Bristol Myers Squibb, Taiho Oncology Jennifer S. MammenStock and Other Ownership Interests: Johnson & Johnson, Bristol Myers SquibbConsulting or Advisory Role: Five Prime Therapeutics Jarushka NaidooHonoraria: Bristol Myers Squibb, AstraZeneca/MedImmune, Merck, Daiichi Sankyo/Lilly, TakedaConsulting or Advisory Role: Bristol Myers Squibb, AstraZeneca/MedImmune, Roche/Genentech, Daiichi Sankyo/Lilly, Takeda, Pfizer, Kaleido BiosciencesResearch Funding: Merck, AstraZeneca, Roche/GenentechTravel, Accommodations, Expenses: Bristol Myers Squibb, AstraZeneca/MedImmune Aung NaingConsulting or Advisory Role: Novartis, CytomX Therapeutics, OncoSec, STCube Pharmaceuticals Inc, Kymab, Takeda (I), CSL Behring (I), Horizon Pharma (I), Genome & CompanyResearch Funding: NCI, EMD Serono, MedImmune, Atterocor, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance BioSciences Inc, Healios, Lilly, Kymab, PsiOxus Therapeutics, Immune Deficiency Foundation (I), Arcus Biosciences, NeoImmuneTech, ImmuneOncia, Surface Oncology, Baxalta (I), Jeffrey Modell Foundation (I), Chao Physician-Scientist AwardsTravel, Accommodations, Expenses: ARMO BioSciences Tanyanika PhillipsTravel, Accommodations, Expenses: City of Hope Alexander SpiraLeadership: NEXT Oncology VirginiaStock and Other Ownership Interests: Eli LillyHonoraria: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol Myers Squibb, BayerConsulting or Advisory Role: Array BioPharma (Inst), Incyte, Amgen, Novartis, AstraZeneca/MedImmune (Inst), Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Merck (Inst), Bristol Myers Squibb (Inst), Takeda, Janssen Research & DevelopmentResearch Funding: Roche (Inst), AstraZeneca (Inst), Boehringer Ingelheim (Inst), Astellas Pharma (Inst), MedImmune (Inst), Novartis (Inst), Newlink Genetics (Inst), Incyte (Inst), AbbVie (Inst), Ignyta (Inst), LAM Therapeutics (Inst), Trovagene (Inst), Takeda (Inst), Macrogenics (Inst), CytomX Therapeutics (Inst), LAM Therapeutics (Inst), Astex Pharmaceuticals (Inst), Bristol Myers Squibb (Inst), Loxo (Inst), Arch Therapeutics (Inst), Gritstone (Inst), Plexxikon (Inst), Amgen (Inst), Loxo (Inst), Daiichi Sankyo (Inst), ADCT (Inst), Janssen Oncology (Inst), Mirati Therapeutics (Inst), Rubius (Inst) Maria Suarez-AlmazorConsulting or Advisory Role: Agile Therapeutics, AMAG Pharmaceuticals¸ Abbvie/Genentech, Avenue Therapeutics, Gilead Sciences, ChemoCentryx, Celgene/Bristol Myers Squibb Umang SwamiConsulting or Advisory Role: Seattle Genetics John A. ThompsonConsulting or Advisory Role: Calithera Biosciences, Clinical Care Options/NCCN, BJ Bioscience, Alpine Immune Sciences, Neoleukin Therapeutics, Academy for Continued Healthcare Learning, Meeting Sites Pro, Regeneron, AVEO, Bristol Myers SquibbResearch Funding: Roche, Pfizer, Agensys, Five Prime Therapeutics, Trillium Therapeutics, Merck, Novartis, Xencor, Five Prime Therapeutics, Incyte Praveen VikasStock and Other Ownership Interests: NovavaxResearch Funding: Sanofi Yinghong WangConsulting or Advisory Role: Tillotts Pharma, Azurrx Pharma Jeffrey S. WeberStock and Other Ownership Interests: CytomX Therapeutics, Biond, Protean Biodiagnostics, NeximmuneHonoraria: Bristol Myers Squibb, Merck, Genentech, AstraZeneca, Daiichi Sankyo, GlaxoSmithKline, Amgen, Roche, Celldex, CytomX Therapeutics, Novartis, Sellas Life Sciences, WindMIL, Takeda, Moderna Therapeutics, Jounce Therapeutics, Kirin Pharmaceuticals, Regeneron, Idera, OncosecConsulting or Advisory Role: Celldex, Bristol Myers Squibb, Merck¸ Genentech, Roche, Amgen, AstraZeneca, GlaxoSmithKline, Daiichi Sankyo, CytomX Therapeutics, Novartis, Sellas Life Sciences, WindMIL, Jounce Therapeutics, Moderna Therapeutics, Kirin Pharmaceuticals, Protean Biodiagnostics, Idera, OncosecResearch Funding: Bristol Myers Squibb, Merck, GlaxoSmithKline, Genentech, Astellas Pharma, Incyte, Roche, Novartis, NextCure (Inst), Moderna Therapeutics (Inst)Patents, Royalties, Other Intellectual Property: Named on a patent submitted by Moffitt Cancer Center for an IPILIMUMAB biomarker, named on a patent from Biodesix for a PD-1 antibody biomarker, and named on a patent for 41BB-induced TIL by Moffitt Cancer CenterTravel, Accommodations, Expenses: Bristol Myers Squibb, GlaxoSmithKline, Roche, Celldex, Amgen, Merck, AstraZeneca, Genentech, Novartis Monalisa GhoshResearch Funding: Celgene (Inst)No other potential conflicts of interest were reported.

Medications used in the treatment of inflammatory bowel disease cause a wide range of dermatologic side effects, and minimal guidance exists on how to manage them. The intention of this review article is to summarize common dermatologic adverse reactions related to inflammatory bowel disease therapy and to provide evidence-based guidance on management. We conducted a scoping review using PubMed and Google Scholar to identify studies reporting clinical information on dermatologic side effects of medications used in the treatment of inflammatory bowel disease. The most commonly reported dermatological adverse effects from inflammatory bowel disease therapy were cutaneous malignancy and cutaneous infections. Thiopurines, methotrexate, tumor necrosis factor (TNF) inhibitors, interleukin (IL)-12/23 inhibitors, and integrin inhibitors can be continued if nonmelanoma skin cancer arises during therapy and the malignancy should be surgically excised. TNF inhibitors and IL-12/23 inhibitors can be continued in the setting of stage I surgically resectable melanoma but should be discontinued in advanced melanoma. For complicated cutaneous bacterial infections, methotrexate and TNF inhibitors should be halted, and IV antibiotics should be administered. Complicated herpes zoster infection warrants discontinuation of TNF inhibitors, whereas IL-12/23 and JAK inhibitors can be continued. Inflammatory bowel disease therapies are associated with several dermatological adverse effects, and management options vary by agent. Certain agents may require discontinuation in the setting of nonmelanoma skin cancer, melanoma, and cutaneous infections. Many other dermatological adverse effects from inflammatory bowel disease therapy require specialized management or referral to dermatology., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Acute anaphylaxis to small molecule drugs is largely considered to be antibody-mediated with immunogloblin E (IgE) and mast cell activation being key. More recently, a role for drug-reactive immunoglobulin G (IgG) with neutrophil activation has also been suggested, at least in reactions to neuromuscular blocking agents (NMBAs). However, the mast cell receptor MRGPRX2 has also been highlighted as a possible triggering mechanism in acute anaphylaxis to many clinically used drugs. Significantly, MRGPRX2 activation is not dependent upon the presence of drug-recognising antibody. Given the reasonable assumption that MRGPRX2 is expressed in all individuals, the corollary of this is that in theory, anybody could respond detrimentally to triggering drugs (recently suggested to be around 20% of a drug-like compound library). But this clearly is not the case, as the incidence of acute drug-induced anaphylaxis is very low. In this mini-review we consider antibody-dependent and -independent mechanisms of mast cell activation by small molecule drugs with a focus on the MRGPRX2 pathway. Moreover, as a juxtaposition to these adverse drug actions, we consider how increased understanding of the role of MRGPRX2 in anaphylaxis is important for future drug development and can complement exploration of this receptor as a drug target in broader clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mackay, Fernandopulle, Ding, McComish and Soeding.)

Purpose: We assessed real-world spectrum and patterns of irAEs for patients treated with anti-PD(L)1 ICIs., Methods: irAEs were defined using medical and pharmacy claims for patients enrolled in a Medicare Advantage Prescription Drug plan who initiated treatment with anti-PD(L)-1 and received ≥ 1 dose of therapy between 1 September 2014 and 28 February 2018., Results: Treatment was discontinued for 46.6% of patients, and withheld and subsequently restarted for 10.3%. While toxicity profiles did not differ by age, RiskRx-V co-morbidity index was higher in patients with irAEs., Conclusion: These data underscore the needs for tailored irAE diagnostic and management pathways.

Background/aim: Recently, the number of patients with cancer receiving outpatient chemotherapy using oral anticancer drugs has increased, but the currently available outpatient cancer chemotherapy is not safer than that available before. The present study aimed to identify risk factors associated with unplanned acute care (UAC) requiring outpatient chemotherapy-related consultation and hospitalisation., Patients and Methods: We conducted a case- control study among 1,674 patients who received oral anticancer drug treatment either alone or in combination with injectable anticancer drugs at National Cancer Center Hospital East, Japan, between December 1, 2014, and November 30, 2015., Results: Body mass index (BMI) was identified as a risk factor for UAC during chemotherapy. Patients with a BMI of <18.5 kg/m 2 , classified as underweight according to the World Health Organization classification of nutritional status, had a significantly higher risk of UAC., Conclusion: A low BMI immediately before the occurrence of chemotherapy-related UAC is a risk factor for adverse effects; therefore, underweight patients need more careful monitoring and supportive care., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using apalutamide plus abiraterone acetate, each of which suppresses the androgen signalling axis in a different way, versus standard care in mCRPC., Methods: ACIS was a randomised, placebo-controlled, double-blind, phase 3 study done at 167 hospitals in 17 countries in the USA, Canada, Mexico, Europe, the Asia-Pacific region, Africa, and South America. We included chemotherapy-naive men (aged ≥18 years) with mCRPC who had not been previously treated with androgen biosynthesis signalling inhibitors and were receiving ongoing androgen deprivation therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a Brief Pain Inventory-Short Form question 3 (ie, worst pain in the past 24 h) score of 3 or lower. Patients were randomly assigned (1:1) via a centralised interactive web response system with a permuted block randomisation scheme (block size 4) to oral apalutamide 240 mg once daily plus oral abiraterone acetate 1000 mg once daily and oral prednisone 5 mg twice daily (apalutamide plus abiraterone-prednisone group) or placebo plus abiraterone acetate and prednisone (abiraterone-prednisone group), in 28-day treatment cycles. Randomisation was stratified by presence or absence of visceral metastases, ECOG performance status, and geographical region. Patients, the investigators, study team, and the sponsor were masked to group assignments. An independent data-monitoring committee continually monitored data to ensure ongoing patient safety, and reviewed efficacy data. The primary endpoint was radiographic progression-free survival assessed in the intention-to-treat population. Safety was reported for all patients who received at least one dose of study drug. This study is completed and no longer recruiting and is registered with ClinicalTrials.gov, number NCT02257736., Findings: 982 men were enrolled and randomly assigned from Dec 10, 2014 to Aug 30, 2016 (492 to apalutamide plus abiraterone-prednisone; 490 to abiraterone-prednisone). At the primary analysis (median follow-up 25·7 months [IQR 23·0-28·9]), median radiographic progression-free survival was 22·6 months (95% CI 19·4-27·4) in the apalutamide plus abiraterone-prednisone group versus 16·6 months (13·9-19·3) in the abiraterone-prednisone group (hazard ratio [HR] 0·69, 95% CI 0·58-0·83; p<0·0001). At the updated analysis (final analysis for overall survival; median follow-up 54·8 months [IQR 51·5-58·4]), median radiographic progression-free survival was 24·0 months (95% CI 19·7-27·5) versus 16·6 months (13·9-19·3; HR 0·70, 95% CI 0·60-0·83; p<0·0001). The most common grade 3-4 treatment-emergent adverse event was hypertension (82 [17%] of 490 patients receiving apalutamide plus abiraterone-prednisone and 49 [10%] of 489 receiving abiraterone-prednisone). Serious treatment-emergent adverse events occurred in 195 (40%) patients receiving apalutamide plus abiraterone-prednisone and 181 (37%) patients receiving abiraterone-prednisone. Drug-related treatment-emergent adverse events with fatal outcomes occurred in three (1%) patients in the apalutamide plus abiraterone-prednisone group (2 pulmonary embolism, 1 cardiac failure) and five (1%) patients in the abiraterone-prednisone group (1 cardiac failure and 1 cardiac arrest, 1 mesenteric arterial occlusion, 1 seizure, and 1 sudden death)., Interpretation: Despite the use of an active and established therapy as the comparator, apalutamide plus abiraterone-prednisone improved radiographic progression-free survival. Additional studies to identify subgroups of patients who might benefit the most from combination therapy are needed to further refine the treatment of mCRPC., Funding: Janssen Research & Development., Competing Interests: Declaration of interests FS received financial support from Janssen for the ACIS study; he reports grants or contracts, consulting fees, and payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Myovant, Novartis, and Sanofi, outside of the submitted work. EE received financial support from Janssen for the ACIS study; she reports grants or contracts from Astellas, AstraZeneca, Janssen, Merck, Oric, and Sanofi; consulting fees from Astellas, AstraZeneca, Bayer, Janssen, Merck, Pfizer, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Bayer, Janssen, and Sanofi; financial support for attending meetings, travel, or both, from Astellas, Janssen, and Sanofi; participated in Data Safety Monitoring Board or Advisory Board meetings for AstraZeneca, Janssen, Merck, Pfizer, and Sanofi; and reports leadership or fiduciary roles in other board, society, committee, or advocacy group, paid or unpaid, for the European Society of Medical Oncology, outside of the submitted work. GA received financial support from Janssen for the ACIS study; he reports grants or contracts from Astellas and Janssen; consulting fees from Astellas, Bayer, Beigene, Clovis, Janssen, Novartis, Pfizer, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Astellas, Bayer, Janssen, Novartis, and Sanofi; financial support for attending meetings, travel, or both, from Astellas, Bayer, Janssen, Novartis, Pfizer, and Sanofi; participated in Data Safety Monitoring Board or Advisory Board meetings for Astellas, Bayer, Janssen, Novartis, Pfizer, and Sanofi; received royalties from Janssen paid to the Institute of Cancer Research; and is included on the list of rewards to discoverers of abiraterone, outside of the submitted work. TWF received grants or contracts from Agensys, Aragon Pharmaceuticals, Astellas Pharma, AstraZeneca–MedImmune, Bristol Myers Squibb, Bavarian Nordic, Dendreon, Exelixis, GTx, Janssen Oncology, La Roche-Posay, Lilly, Medivation, Merck, Novartis, Pfizer, Roche–Genentech, Sanofi, Sotio, Seagen, Seattle Genetics, and Tokai Pharmaceuticals; consulting fees from Aurora Oncology, Janssen Oncology, and Seattle Genetics; filed two patents (via the University of Colorado) related to early-stage bladder cancer treatment and detection for which he is an inventor, neither of which are currently commercialised or in clinical trials; and is the founder and a stockholder for Aurora Oncology, all outside of the submitted work. OBG received consulting fees from Bayer and Janssen and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, and educational events from Janssen, all outside of the submitted work. SO reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings, travel, or both from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, Janssen, Merck, Novartis, Pfizer, and Sanofi and participated in Data Safety Monitoring Board or Advisory Board meetings for Astellas, Janssen, Roche, and Sanofi, all outside of the submitted work. TS received consulting fees and payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Astellas Oncology, Bayer Health, Janssen, and Sanofi, all outside of the submitted work. HS received financial support from Janssen for the ACIS study; he reports grants or contracts from Asahi Kasei, Bayer, Daiichi Sankyo, Kissei, Nippon Kayaku, Nippon Shinyaku, Ono, Sanofi, Taiho, and Takeda; consulting fees from Astellas, AstraZeneca, Bayer, Eli Lilly, Janssen, MSD, Nihon Medi-Physics, Roche–Chugai, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, and manuscript writing or educational events from Astellas, AstraZeneca, Bayer, Janssen, Merck Biopharma, MSD, Nippon Shinyaku, Ono, Otsuka, Pfizer, Sanofi, and Takeda; support for attending meetings, travel, or both from Astellas, Bayer, Eli Lilly, Janssen, and Sanofi; and participated in Advisory Board meetings for Astellas, Bayer, Janssen, Roche–Chugai, and Sanofi, outside of the submitted work. DER received support from Janssen for the ACIS study; she reports uncompensated participation in advisory boards for AstraZeneca, Bayer, Genentech, Janssen, and Myovant, outside of the submitted work. DW, KY, PDP, SB-M, SL, JL, ST, KBB, SDM, and SAM are employed by Janssen Research & Development, and hold stock in Johnson & Johnson. FF declares no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cancer immunotherapy, which leverages features of the immune system to target neoplastic cells, has revolutionized the treatment of cancer. The use of these therapies has rapidly expanded in the past two decades. Immune checkpoint inhibitors represent one drug class within immunotherapy with its first agent FDA-approved in 2011. Immune checkpoint inhibitors act by disrupting inhibitory signals from neoplastic cells to immune effector cells, allowing activated T-cells to target these neoplastic cells. Unique adverse effects associated with immune checkpoint inhibitors are termed immune-related adverse effects (irAEs) and are usually immunostimulatory in nature. Almost all organ systems may be affected by irAEs including the dermatologic, gastrointestinal, pulmonary, endocrine, and cardiovascular systems. These effects range from mild to life-threatening, and their onset can be delayed several weeks or months. For mild irAEs, symptomatic care is usually sufficient. For higher grade irAEs, discontinuation of therapy and initiation of immunosuppressive therapy may be necessary. The management of patients with irAEs involves multidisciplinary care coordination with respect to the long-term goals the individual patient. Clinicians must be aware of the unique and sometimes fatal toxicologic profiles associated with immunotherapies to ensure prompt diagnosis and appropriate management., (© 2021. American College of Medical Toxicology.)

Introduction: Ibrutinib is a highly effective drug for patients with chronic lymphocytic leukemia (CLL), and is well tolerated even by older patients and those unfit to receive conventional immuno-chemotherapy., Areas Covered: The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world. Ibrutinib-induced lymphocytosis carries the risk of an untimely interruption of therapy because it may be misinterpreted as disease progression. In addition, drug interactions can worsen ibrutinib-associated toxicities by increasing the plasma concentration of ibrutinib. In this review, we present a case of major hemorrhage and atrial fibrillation (AF) during ibrutinib use and summarize the adverse events associated with ibrutinib. Furthermore, the practical management of ibrutinib-associated toxicities was covered with reference to a drug interaction mechanism., Expert Opinion: Clinicians should examine the prescribed drugs prior to ibrutinib initiation and carefully monitor toxicities while taking ibrutinib. A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits. Reducing unexpected toxicities is as significant as achieving treatment response in the era of life-long therapy with ibrutinib in patients with CLL.

Background: Synthetic cathinone abuse is a global health issue. Synthetic cathinones emerged in Taiwan in 2009, and their prevalence rapidly rose. They are usually made into "instant coffee packets," and these so-called "toxic coffee packets" may also contain psychoactive drugs other than synthetic cathinones. Due to the diversity of the ingredients, clinical presentations can be complex., Methods: Retrospective analysis of emergency department (ED) patients who reported ingesting toxic coffee packets at three Chang-Gung Memorial Hospitals located in northern Taiwan between January, 2015 and December, 2019., Results: Sixty patients were included. Their mean age was 28.85 ± 9.24 years and 47(78.33%) were male. The most common presentations were palpitation, agitation, hallucination, and altered consciousness. Tachycardia and hypertension were common, while hyperthermia was observed in only three patients. Three patients (5%) developed rhabdomyolysis, and one underwent transient hemodialysis. Most patients were discharged from the ED, but 15(25%) were admitted, of whom nine (15%) were admitted to the intensive care unit (ICU), and one eventually died. Confirmation tests (mass-spectrometry-based analysis) were available in 10 patients; all reported positive for at least one type of synthetic cathinone. Polysubstance exposure was common. In multivariate logistic regression analyses, Glasgow coma scale ≤13 and the presence of seizure were associated with ICU admission., Conclusion: Patients who report ingesting toxic coffee packets are very likely to have been exposed to synthetic cathinones. Polysubstance exposure is common following ingestion. Cardiovascular and neurological symptoms are the main presentations, and severe complications such as rhabdomyolysis and life-threatening dysrhythmia can occur.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of typical chemotherapeutics among cancer survivors. Despite the recent progress, the effective prevention and treatment strategies for CIPN remain limited. Better understanding of the pathogenesis of CIPN may provide new niches for developing a new ideal therapeutic strategy. This review summarizes the current understanding of CIPN and current recommendations along with completed/active clinical trials and aims to foster translational research to improve the development of effective strategies for managing CIPN.

Background: Adverse drug events (ADE) represent one of the main causes of admission to emergency department (ED). Their detection, documentation, and reporting are essential to avoid readmission. We hypothesize that a pharmacist-initiated multidisciplinary transition of care program combining ED pharmacist contribution and medications' data transfer between inpatient and outpatient caregivers will reduce emergency visits related to ADE METHOD/DESIGN: This is a prospective, open-label, randomized controlled trial. The primary aim of the study is 6-month ED readmission related to the same ADE. Three hundred forty-six adult patients with an ADE detected by a binomial pharmacist-physician will be recruited from the ED of an University Hospital and will be randomized in two groups: [1] experimental group (multidisciplinary transition of care program and medications' data transfer between inpatient and outpatient caregivers) and [2] control group (usual care). Patients will be followed up over a period of 6 months. Endpoints will be carried out blindly of the randomization arm. The primary endpoint is the rate of patients who had at least one readmission in the ED for the same reason at 6 months (data collected during a phone call with the patient and the general practitioner). Trials registered NCT03725046., Discussion: The trial results will have implications for the role of the clinical pharmacist in an emergency department. If successful, the intervention could be considered for implementation across other hospitals., Trial Registration: ClinicalTrials.gov NCT03725046 . Registered on 30 October 2018., (© 2021. The Author(s).)

Pediatric hematologic and oncologic emergencies are in 3 major categories: complications of hematologic disorders, emergencies associated with the new onset of cancers, and treatment-associated oncologic emergencies. The overall number of these patients remains low; however, the mortality associated with these diseases remains high despite significant advances in management. This article presents a review of the most commonly encountered pediatric hematologic and oncologic complications that emergency physicians and providers need to know., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: To compare toxicity and all-cause mortality for mCRPC patients receiving first line oral systemic therapy prescribed by medical oncologists and urologists., Methods: Population-based retrospective cohort study of chemotherapy-naïve men aged ≥66 years treated for mCRPC with first-line abiraterone or enzalutamide based on administrative health data (Ontario, Canada, 2012-2017). Primary outcomes were hospitalizations/ER visits for any cause or treatment-related toxicity during first-line mCRPC treatment. Secondary outcome was all-cause mortality. We calculated hazard ratios (HRs) comparing outcomes for different medical specialties using multivariable Cox proportional hazards models., Results: Among 3405 mCRPC patients, 2407 (70.7%) received abiraterone and 998 (29.3%) received enzalutamide. 1786 (52.5%) patients visited the ER or were hospitalized. Men treated by medical oncologists had an increased risk of hospitalization/ER visits (HR1.16, 95%CI 1.03-1.31; P = .02), toxicity-related visits (HR1.34, 95%CI 1.08-1.69; P = .01), and mortality (HR1.16, 95%CI 1.02-1.33; P = .02) compared to urologists. Limited information was available, beyond PSA adjustment and prior treatment, on patient disease burden., Conclusion: We observed fewer hospital visits overall and for treatment-related toxicity for mCRPC patients who were prescribed first line abiraterone or enzalutamide by urologists compared to medical oncologists. These differences may result from higher prostate cancer disease burden in patients managed by medical oncologists, and/or other unmeasured differences in patient management between specialties., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Severe cutaneous adverse reactions to medications (SCARs) include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. They are all non-immunoglobulin E mediated hypersensitivity reaction patterns, distinguished from simple cutaneous drug eruptions by immunologic pathogenesis and internal organ involvement. Herein the clinical features, diagnostic workup, and management considerations are presented for each of these major SCARs., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The growing availability of more effective therapies has contributed to an increased survival of patients with breast cancer. In hormone receptor-positive early disease, increased survival is strongly correlated with the use of adjuvant endocrine therapy, but this therapy can cause side-effects that have major consequences in terms of treatment adherence and patients' quality of life. In premenopausal breast cancer survivors, these side-effects might be even more prominent due to the abrupt suppression of oestrogen associated with the most intense endocrine therapies. An important ambition of cancer care in the 21st century is to recover pre-cancer quality of life and emotional and social functions, which is only possible through the mitigation of the side-effects of anticancer treatments. This Review presents a comprehensive summary of the efficacy and safety data of the available interventions (hormonal and non-hormonal pharmacological strategies, non-pharmacological approaches, and complementary and alternative medicine) to control selected side-effects associated with adjuvant endocrine therapy (hot flashes, sexual dysfunction, weight gain, musculoskeletal symptoms, and fatigue), providing updated, evidence-based approaches for their management., Competing Interests: Declaration of interests LDM reports an advisory role for Roche, Novartis, Merck Sharp and Dohme, Pfizer, Ipsen, AstraZeneca, Genomic Health, Lilly, Seattle Genetics, Eisai, Pierre Fabre, and Daiichi Sankyo; honoraria from Roche, Novartis, Lilly, and Merck Sharp and Dohme; and travel grants from Roche, Pfizer, and Celgene. IV-L reports honoraria paid to institution from AstraZeneca, Amgen, and Pfizer. EdA reports honoraria from and an advisory board for Roche; and travel grants from Roche, and Novartis; research grants from Roche, Radius, AstraZeneca, Lilly, Merck Sharp and Dohme, Novartis, Synthon, Servier, and Pfizer paid to Institut Jules Bordet. AHP reports royalty payments for coauthoring the breast cancer survivorship section of UpToDate. ML reports an advisory role for Roche, Lilly, AstraZeneca, and Novartis; and honoraria from Pfizer, Lilly, Takeda, Novartis, Roche, and Sandoz. All other authors declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Cancer immunotherapies are associated with remarkable therapeutic response rates but also with unique and severe toxicities, which potentially result in rapid deterioration in health. The number of clinical applications for novel immune effector-cell therapies, including chimeric antigen receptor (CAR)-expressing cells, and other immunotherapies, such as immune-checkpoint inhibitors, is increasing. In this Consensus Statement, members of the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Hematopoietic Cell Transplantation-Cancer Immunotherapy (HCT-CI) Subgroup, Paediatric Diseases Working Party (PDWP) of the European Society of Blood and Marrow Transplantation (EBMT), Supportive Care Committee of the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC) and MD Anderson Cancer Center CAR T Cell Therapy-Associated Toxicity (CARTOX) Program collaborated to provide updated comprehensive recommendations for the care of children, adolescents and young adults receiving cancer immunotherapies. With these recommendations, we address emerging toxicity mitigation strategies, we advocate for the characterization of baseline organ function according to age and discipline-specific criteria, we recommend early critical care assessment when indicated, with consideration of reversibility of underlying pathology (instead of organ failure scores) to guide critical care interventions, and we call for researchers, regulatory agencies and sponsors to support and facilitate early inclusion of young patients with cancer in well-designed clinical trials.

Monoamine oxidase inhibitors (MAOIs) were among the first licensed pharmacological treatments for patients with depression but over time have fallen out of mainstream clinical use. This has led to a loss of clinician training opportunities and reduced availability of MAOIs for prescribing. This article provides a concise and practical overview of how to use MAOIs safely and effectively in psychiatric practice. We consider the history of MAOIs, why they are not used more frequently, their mechanisms of action, availability, indications and efficacy, general tolerability, withdrawal symptoms, and safety considerations (including hypertensive reactions and serotonin syndrome). Practical advice is given in terms of dietary restrictions, interactions with other medications (both prescribed and non-prescribed), and how prescribers can stop and switch MAOIs, both within the drug class and outside of it. We also provide advice on choice of MAOI and treatment sequencing. Lastly, we consider emerging directions and potential additional indications., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Drug-induced iatrogenic toxicities are common in critically ill patients and have been associated with increased morbidity and mortality. Early recognition and management of iatrogenic toxicities is essential; however, the diagnosis is usually complicated by the underlying critical illness, comorbidities, and administration of multiple medications. This article reviews several types of iatrogenic toxicities associated with medications that are commonly used in critically ill patients. The mechanism of the iatrogenic toxicities, clinical presentation, and diagnosis, as well as management are discussed., Competing Interests: Disclosure No financial disclosures. No conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

SARS CoV-2 virus has infected more than 200 million people worldwide and more than 4.4 million in Indonesia. The vaccination program has become one of the solutions launched by many countries globally, including Indonesia, to reduce the transmission rate of COVID-19. Various vaccination platforms are produced, such as inactivated, viral vector, mRNA, and protein subunit. The vaccination booster program with mRNA platform (Moderna) was launched by the Indonesian government to give better protection for health care workers, particularly from delta variant. In this case report, we discuss one of the typical side effects of Moderna vaccine, which is referred to as the COVID arm.

Purpose of Review: The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase's most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit., Recent Findings: Clinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The majority of these toxicities are temporary, nonfatal, and can be managed supportively without permanent pegaspargase discontinuation. Special attention should be paid to inactivation, which can lead to treatment failure, as well as pancreatitis, which necessitates complete cessation of asparaginase therapy. The question of how to best proceed in patients who cannot tolerate pegaspargase remains unanswered, and is an important area of future investigation. Pegaspargase is an essential component of the pediatric-inspired regimens that have improved survival in adult ALL. Although pegaspargase's toxicity profile is unique, it is also highly manageable and should not be a barrier to achieving maximum clinical benefit using this drug.

Cancer and oncologic therapies can have significant adverse effects on male reproductive potential, leaving many men permanently infertile. Fertility preservation has emerged as a key survivorship issue over the past 20 years, and numerous professional societies have published guidelines calling for fertility preservation to become a routine component of oncologic care. Most males with cancer are able to produce a semen specimen for fertility preservation, but numerous other methods of sperm procurement are available for patients who cannot provide a sufficient sample. Despite these options, fertility preservation will remain a challenge for prepubertal boys and men without sperm production. For these patients, experimental and investigational approaches offer the hope that one day they will translate to the clinical arena, offering additional pathways for successful fertility preservation care., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Intravesical therapy for nonmuscle invasive bladder cancer decreases recurrence and progression but carries a high risk of side effects, which limit patient adherence. Appropriate management of the toxicities from intravesical therapy requires consideration of the agent used, the side effects experienced, and the timing of those side effects. Management strategies for intravesical toxicities ideally improve patient tolerance without sacrificing oncologic outcomes. This review aims to provide a comprehensive overview of the available evidence regarding the side effects of intravesical therapies for nonmuscle invasive bladder cancer and to propose practical strategies for toxicity management., (Copyright © 2020. Published by Elsevier Inc.)

Neurologic adverse effects of triazole antifungal compounds used for the treatment of systemic and deep mycoses are relatively rare. The most common presentation is the involvement of peripheral nervous system, usually presenting with subjective symptoms such as paresthesia, dysesthesia, or numbness. Among these compounds, fluconazole has relatively more frequent neurological adverse reactions.A 54-year-old man was admitted with numbness and weakness in his both feet, which gradually worsened and resulted in difficulty in ambulation over time. He had no morbidity other than hypertension. He developed polyneuropathy (PNP), lower gastrointestinal system bleeding, acute renal insufficiency, thrombotic thrombocytopenic purpura, and confusional state. Severely disabling axonal and demyelinating sensorimotor PNP which led to immobilization of the patient for a few weeks but was recovered. When a more detailed past medical history was taken, he admitted to ingestion of 200 mg/day fluconazole for 1 month for onychomycosis without any prescription. This unusual combination of these rare adverse reactions of fluconazole may be explained by activation of an immune mechanism triggered by the drugs and genetic factors, or some other unknown individual factors.This case is reported due to the presence of rare systemic and neurologic adverse events of fluconazole, leading to this unusual clinical picture. We would like to emphasize fluconazole-related systemic and neurologic adverse reactions with life-threatening potential should be kept in mind.

Use of molecular targeting agents and immune checkpoint inhibitors (ICIs) has increased the frequency and broadened the spectrum of lung toxicity, particularly in patients with cancer. The diagnosis of drug-related pneumonitis (DRP) is usually achieved by excluding other potential known causes. Awareness of the incidence and risk factors for DRP is becoming increasingly important. The severity of symptoms associated with DRP may range from mild or none to life-threatening with rapid progression to death. Imaging features of DRP should be assessed in consideration of the distribution of lung parenchymal abnormalities (radiologic pattern approach). The CT patterns reflect acute (diffuse alveolar damage) interstitial pneumonia and transient (simple pulmonary eosinophilia) lung abnormality, subacute interstitial disease (organizing pneumonia and hypersensitivity pneumonitis), and chronic interstitial disease (nonspecific interstitial pneumonia). A single drug can be associated with multiple radiologic patterns. Treatment of a patient suspected of having DRP generally consists of drug discontinuation, immunosuppressive therapy, or both, along with supportive measures eventually including supplemental oxygen and intensive care. In this position paper, the authors provide diagnostic criteria and management recommendations for DRP that should be of interest to radiologists, clinicians, clinical trialists, and trial sponsors, among others., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aim: Continuous renal replacement therapy (CRRT) has significant benefits in the treatment of critically ill children. The objective of this study is to describe the treatment indications, methods, demographics, and outcome of the patients who received CRRT in our pediatric intensive care unit and neonatal care unit, and, according to these results, we also aim to make improvements in our unit-based interventions., Material and Methods: In this single-centered study, we retrospectively evaluated medical charts of the patients admitted to our intensive care units and received CRRT between February 2010 and November 2015., Results: Fifty of 60 patients were included in this study. Newborns made up 28% (n = 14) of the patients. The mean body weight was 18.4 kg (2.3-98 kg). CRRT indications were fluid overload (30%), acute kidney injury (40%), metabolic disease (24%), electrolyte impairment (4%), and drug intoxication (2%). The most common method of CRRT was continuous venovenous hemodiafiltration (CVVHDF) (72%). The mean duration of CRRT was 135 hours (1-864) and totally 143 filters, polyarylethersulfon (n = 23.46%) and polyacrylonitrile (n = 27.54%) were used. Overall survival was 42%. The survival rate of newborns was significantly higher (P = 0.046)., Conclusion: CRRT is a lifesaving method that can be applied to critically ill children with acute kidney injury and fluid overload at any age and weight by experienced teams., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Purpose: Aromatase inhibitor (AI)-associated symptoms contribute to early therapy discontinuation. Although guidelines exist for management of these symptoms, little is known about the degree to which physicians address symptoms and adhere to the guidelines for treatment., Patients and Methods: In this retrospective chart review, women with hormone receptor-positive breast cancer who were prescribed an AI between October 15, 2012, and September 14, 2017, were randomly selected from the institution's cancer registry. Patient medical records were reviewed to identify the prevalence of symptom documentation and management. Documented symptoms were categorized into musculoskeletal, vasomotor, and urogenital. Symptom treatment guidelines were compiled from the National Comprehensive Cancer Network (NCCN) and the American Cancer Society/American Society of Clinical Oncology (ACS/ASCO). Treatments were categorized as either meeting or not meeting the guidelines. Among patients with symptoms recorded, chi-square tests and time-to-event models were used to examine factors associated with treatment and factors associated with guideline-based treatment., Results: Among 179 women prescribed an AI, 82% had at least one symptom and 46% had multiple symptoms. Of the 147 women with any documented symptom, 97 (66%) received some form of symptom-palliating treatment. Seventy-seven patients (52%) received guideline-based treatments or guideline-based treatments in combination with non-guideline-based treatments. There were no differences in receipt of treatment overall (ie, guideline based or non-guideline based) for either vasomotor or musculoskeletal symptoms by age, race, or stage., Conclusion: Although 82% of patients had symptoms documented in their medical records, just over half of those patients received guideline-based treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Taste changes are commonly reported by people with cancer undergoing radio- or chemotherapy. Taste changes may compromise dietary intake and nutritional status., Objective: To understand whether or not taste change is associated with cancer diagnosis or treatment modality in adults., Methods: A systematic literature search up to December 31, 2019, was conducted using PubMed, Embase, and PsycInfo (International Prospective Register of Systematic Reviews protocol no. CRD42019134005). Studies in adults with cancer objectively assessing the effect of a cancer diagnosis or chemotherapy and/or radiotherapy treatment on taste function compared with healthy controls or within participant changes were included. Additional outcomes were food liking, appetite, dietary intake, nutritional status, and body composition. Reference lists of relevant articles were searched to identify additional articles. Quality was assessed using the Academy of Nutrition and Dietetics quality criteria checklist., Results: A total of 24 articles were included, one of which consisted of two studies that reported the effects of radiotherapy and chemotherapy separately. From the total 25 studies reported in 24 published articles, 14 studies examined effects of radiotherapy, and remaining 11 studies examined chemotherapy. There is limited evidence of a cancer diagnosis per se contributing to taste dysfunction. Impaired taste function was reported in almost all radiotherapy studies, occurring as early as Week 3 of treatment and lasting for 3 to 24 months posttreatment. During chemotherapy, impairment of taste function was less consistently reported, occurring as early as the first few days of chemotherapy, and persisting up to 6 months posttreatment. Taxane-based chemotherapy was reported to affect taste function more than other treatments. Several studies reported reduced liking for food, appetite, and dietary intake. Only one study reported nutritional status of participants, finding no association between taste function and nutritional status. No studies examined associations between taste changes and body composition., Conclusions: This review highlights the importance of considering treatment modality in practice. Research is required to identify factors contributing to taste alteration and to inform evidence-based interventions., (Copyright © 2021 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Immune checkpoint inhibitors (ICIs) have emerged as the newest pillar of cancer treatment. Immune-mediated toxicities, stemming from increased activity within the T cell lineage, range from asymptomatic or mild complications to those that are fulminant and potentially fatal. Although they are of variable occurrence, cardiovascular, rheumatic, and renal immune-mediated toxicities are among the most serious of these adverse events. We present MASCC recommendations with respect to the workup and management of cardiovascular, rheumatic, and renal immune-mediated toxicities with a focus on presentations that require treatment with immunomodulating agents.