“…Neurologic irAEs are uncommon, but have many forms. ICIassociated complications involving the peripheral nervous system include polyradiculopathies, neuropathies, myasthenic syndromes and myopathies, whereas the central nervous system can be affected by aseptic meningitis and encephalitis (Chhabra and Kennedy, 2021;Roth et al, 2021). Imaging, cerebrospinal fluid diagnostic, electroencephalography/ electromyoneurography and laboratory assessments help exclude tumor progression, vascular complications, infections, epilepsy, metabolic or toxic conditions and side effects of previous or current therapies.…”
Section: Neurotoxicitymentioning
confidence: 99%
“…If neurological irAEs grade ≥2 are considered, ICI treatment should be interrupted and systemic steroids initiated (Haanen et al, 2017;Chhabra and Kennedy, 2021;Roth et al, 2021). For patients experiencing grade 2 neurotoxicity, it is prednisolone 0.5-1 mg/kg.…”
Section: Neurotoxicitymentioning
confidence: 99%
“…The pathophysiological mechanism is not yet fully understood, but irAEs are considered to be T cell mediated and mark the reinvigorated immune system which may cause organ-specific inflammation, tissue damage and autoimmunity (Chhabra and Kennedy, 2021). Activation of the complement may also play a role in the process (Roth et al, 2021). The most frequently affected tissues are skin, gastrointestinal system, endocrine glands, liver and lungs, but irAEs may involve any organ system.…”
Immune checkpoint inhibitors (ICIs), especially those targeting the programmed-death 1 (PD-1) receptor and its ligands, have become indispensable agents in solid tumor anti-cancer therapy. Concerning hematological malignancies, only nivolumab and pembrolizumab have been approved for the treatment of relapsed and refractory classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma to date. Nevertheless, clinical research in this field is very active. The mechanism of action of ICIs is based on unblocking the hindered immune system to recognize and eliminate cancer cells, but that also has its costs in the form of ICI-specific immune related adverse events (irAEs), which can affect any organ system and can even be lethal. In this article, we have reviewed all prospective blood cancer clinical trials investigating ICIs (both monotherapy and combination therapy) with available toxicity data with the purpose of determining the incidence of irAEs in this specific setting and to offer a brief insight into their management, as the use of immune checkpoint blockade is not so frequent in hemato-oncology.
“…Neurologic irAEs are uncommon, but have many forms. ICIassociated complications involving the peripheral nervous system include polyradiculopathies, neuropathies, myasthenic syndromes and myopathies, whereas the central nervous system can be affected by aseptic meningitis and encephalitis (Chhabra and Kennedy, 2021;Roth et al, 2021). Imaging, cerebrospinal fluid diagnostic, electroencephalography/ electromyoneurography and laboratory assessments help exclude tumor progression, vascular complications, infections, epilepsy, metabolic or toxic conditions and side effects of previous or current therapies.…”
Section: Neurotoxicitymentioning
confidence: 99%
“…If neurological irAEs grade ≥2 are considered, ICI treatment should be interrupted and systemic steroids initiated (Haanen et al, 2017;Chhabra and Kennedy, 2021;Roth et al, 2021). For patients experiencing grade 2 neurotoxicity, it is prednisolone 0.5-1 mg/kg.…”
Section: Neurotoxicitymentioning
confidence: 99%
“…The pathophysiological mechanism is not yet fully understood, but irAEs are considered to be T cell mediated and mark the reinvigorated immune system which may cause organ-specific inflammation, tissue damage and autoimmunity (Chhabra and Kennedy, 2021). Activation of the complement may also play a role in the process (Roth et al, 2021). The most frequently affected tissues are skin, gastrointestinal system, endocrine glands, liver and lungs, but irAEs may involve any organ system.…”
Immune checkpoint inhibitors (ICIs), especially those targeting the programmed-death 1 (PD-1) receptor and its ligands, have become indispensable agents in solid tumor anti-cancer therapy. Concerning hematological malignancies, only nivolumab and pembrolizumab have been approved for the treatment of relapsed and refractory classical Hodgkin lymphoma and primary mediastinal large B cell lymphoma to date. Nevertheless, clinical research in this field is very active. The mechanism of action of ICIs is based on unblocking the hindered immune system to recognize and eliminate cancer cells, but that also has its costs in the form of ICI-specific immune related adverse events (irAEs), which can affect any organ system and can even be lethal. In this article, we have reviewed all prospective blood cancer clinical trials investigating ICIs (both monotherapy and combination therapy) with available toxicity data with the purpose of determining the incidence of irAEs in this specific setting and to offer a brief insight into their management, as the use of immune checkpoint blockade is not so frequent in hemato-oncology.
“…Erhöhte Zytokinwerte Erhöhte Zytokinwerte im Liquor können hilfreich sein, ebenso eine bildmorphologische Kontrastmittelanhebung der Meningen Kontrastmittelanhebung der Meningen . Dokumentierte Beobachtungen aseptischer Meningitiden gibt es unter Immuncheckpoint-Therapie [ 23 ] und auch unter dem Multikinaseinhibitor Regorafenib [ 24 ]. In der Regel ist dieses Krankheitsbild steroidresponsiv steroidresponsiv , sodass eine Prednisolontherapie bereits zügig zu einer Verbesserung führen kann (siehe auch Tab.…”
ZusammenfassungDie onkologische Behandlung ist biomarkerbasierter, molekular maßgeschneiderter und effektiver geworden. Aufbauend auf der zunehmenden Entschlüsselung zellbiologischer und molekularer Mechanismen steigt auch die Zahl zielgerichteter medikamentöser Therapien. Es steigt zudem die Zahl der Langzeitüberlebenden. Eine neuro(onko)logische Betreuung wird immer wichtiger, nicht nur wegen vermehrter direkter tumorbedingter Symptome – wie etwa der höheren Inzidenz einer Metastasierung in das Zentralnervensystem –, sondern weil im Zuge dieser modernen onkologischen systemischen Therapieformen ein breites Spektrum therapieassoziierter neurologischer Symptome auftritt, die einer sorgfältigen und raschen neurologischen/neuroonkologischen Evaluation und Therapiekonzeption bedürfen. Das Ziel dieses Artikels ist es, das Bewusstsein für die häufigsten therapieassoziierten neurologischen Symptome zu schärfen.
“…Furthermore, stimulation of the complement system may also cause inflammation. Among the tissues, which are commonly altered by immunotherapy, are the pituitary gland and thyroid, skin, liver, colon, lung, kidney, joints muscles, and nervous system [31].…”
Section: Introduction 1general Considerations On Tumor Immunotherapymentioning
Conventional chemotherapy has partial therapeutic effects against hematological malignancies and is correlated with serious side effects and great risk of relapse. Recently, immunotherapeutic drugs have provided encouraging results in the treatment of hematological malignancies. Several immunotherapeutic antibodies and cell therapeutics are in dynamic development such as immune checkpoint blockades and CAR-T treatment. However, numerous problems restrain the therapeutic effectiveness of tumor immunotherapy as an insufficient anti-tumor immune response, the interference of an immune-suppressive bone marrow, or tumoral milieu with the discharge of immunosuppressive components, access of myeloid-derived suppressor cells, monocyte intrusion, macrophage modifications, all factors facilitating the tumor to escape the anti-cancer immune response, finally reducing the efficiency of the immunotherapy. Nanotechnology can be employed to overcome each of these aspects, therefore having the possibility to successfully produce anti-cancer immune responses. Here, we review recent findings on the use of biomaterial-based nanoparticles in hematological malignancies immunotherapy. In the future, a deeper understanding of tumor immunology and of the implications of nanomedicine will allow nanoparticles to revolutionize tumor immunotherapy, and nanomedicine approaches will reveal their great potential for clinical translation.
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