EFECTOS SECUNDARIOS DE LA INMUNOTERAPIA · -D37: o Hipertiroidismo primario autoinmune en relación con inmunoterapia. Mejoría analítica espontánea-D44o Exploración: el paciente

EFECTOS SECUNDARIOS DE LA INMUNOTERAPIA

AMPAROBURGOSSANJOSÉFARMACÉUTICAADJUNTABCOPHOSPITALGENERALUNIVERSITARIODEALICANTE

irAEs relacionados con los ICIs. Tomada de Varrichi et al.

DRESS drug rash with eosinophilia and systemic syntoms

Varrichi et al. Cardiotoxicity of immune checkpoint inhibitors. ESMO Open 2017;2:e000247.doi:10.1136/esmoopen-2017-000247 Varrichietal.ESMOOpen2017;2:e000247.doi:10.1136/esmoopen-2017-000247

Ø Varón de 71 añosØ Peso:88 kg, Talla:1,79 mØ Exfumador de 40 años/paquete desde hace 8 añosØ Antecedentes médicos:

Ø HTA (sin tratamiento)Ø Hipotiroidismo controlado con Levotiroxina (Eutirox®) 75 mcgØ HBPØ GlaucomaØ No diabetesØ No DLPØ No RAMs

Ø CPNM epidermoide con metástasis suprarrenal izquierda y renal (IVB) Ø PS1 y PD-L1 neg

AJCCCancerstagingmanual.8thed.classification until 2018. This potentially means that dataduring 2017 from the United States and the rest of the worldwill not be entirely compatible. The question arises as towhat US institutions that were ready and poised to adoptthe new classification on January 1, 2017, should do.Although the data filed by tumor registrars must be that ofthe seventh edition until 2018, clinicians and institutionsin the United States may decide to record both, so that thedata can be aligned with that of the rest of the world. Ifthis policy is adopted, it is essential that everyone notonly document a stage classification but also the editionused, for example T1bN1M0 (seventh edition)/T1cN1M0(eighth edition).

How does the new stage classification affect clinicianscaring for patients with lung cancer? The availability of alarge data set promotes greater granularity, allowing us todescribe more specific tumor characteristics. In turn, thisprovides a mechanism to define treatment outcomes for

more specific subgroups of patients. For example, it mayhelp us define the role of adjuvant chemotherapy for varyingsizes of N0M0 tumors. It is crucial to note, however that it isthe outcome of patients treated in a defined way in clinicalstudies that defines the best treatment approach, not thename put on a particular tumor by the stage classification.The nature of a tumor, its behavior, and its response to atreatment strategy is the same no matter what name weput on it. Greater granularity only provides a tool that helpsus communicate clearly.

People often point to other tumor characteristics that mayaffect the choice of treatment and the resultant prognosis(eg, the presence of genetic mutations) and wonder whythey are not part of the stage classification. Stage classifica-tion specifically provides a description of the anatomicextent of disease, however, thus providing a tool to describeone (major) component of how to discriminate patients thatare appropriately treated in a certain fashion. There aremany other characteristics that also influence the choiceof treatment in specific settings, such as mutations inadvanced stage tumors being considered for targetedtherapy, pulmonary reserve in patients with early stagedisease being considered for resection, age, comorbidities,and so on.

Similarly, the anatomic burden of disease is one aspectthat affects prognosis, along with many other factors suchas patient characteristics (eg, age and comorbidities), tumorfactors (eg, histotype and molecular characteristics), envi-ronmental factors (eg, access to care and geographic re-gion), and treatment-related factors (eg, treatmentreceived, quality of care, and response to treatment). Foraggressive and advanced stage cancers, prognosis may beoverwhelmingly determined by the anatomic tumor extent.In other settings, however, such as less aggressive oradvanced tumors, prognosis is determined largely by otherfactors, such as general health, age, and effectiveness of the

FIGURE 1. Lung cancer stage grouping (eighth edition).

TABLE 2. Key features distinguishing the eighth edition classification

Tumor size is determined by the largest dimension of the solid portion by

computed tomography* (clinical) or the invasive portiony(pathologicz).

Tumor size is subdivided in 1-cm increments up to 5 cm.

Tumors>5 but !7 cm are classified as T3.Tumors>7 cm are classified as T4.

Tumors involving the main stem bronchus or causing lung atelectasis or

obstructive pneumonitis are classified as T2 regardless of distance

from the carina or whether they cause partial or total lung atelectasis.

Tumors involving the diaphragm are classified as T4.

Tumors involving a single distant (extrathoracic) site are classified as

M1b.

Tumors involving multiple distant sites are classified as M1c.

*With lung window settings, 1-mm slice thickness. yIf several areas of solid and inva-sive tumor are present, multiply the largest total dimension (including the groundglass or lepidic components) by the proportion that is solid (imaging) or invasive (his-tologic). zNevertheless, the largest total dimension (including the ground glass orlepidic components) should be additionally noted.

358 The Journal of Thoracic and Cardiovascular Surgery c January 2018

Thoracic: Feature Expert Opinion: Lung Cancer Detterbeck

THOR

MajemM,JuanO,InsaAandcol. SEOMclinicalguidelinesforthetreatmentofnon-smallcelllungcancer(2018)

Ø Cisplatino-Gemcitabina cada 21 días (4 CICLOS)

Ø TAC craneal- TAP: empeoramiento radiológico evidente de las lesiones pulmonares y renales

MajemM,JuanO,InsaAandcol. SEOMclinicalguidelinesforthetreatmentofnon-smallcelllungcancer(2018)

- D1: Nivolumab 240 mg (1ª dosis)

- D15: Nivolumab 240 mg (2ª dosis)

- D29 : Nivolumab 240 mg (3ª dosis)

- D37: Ingreso hospitalario por ptosis bilateral asimétrica (mayor en OD)TAC craneal y RM encefálica descartan metástasis SNC

§ D1: Nivolumab 240 mg (1ª dosis).

Día 1 -ONCO

Día 15 -ONCO

Día 29 –ONCO

§ D15: Nivolumab 240 mg (2ª dosis).

JC: Hipertiroidismo primario autoinmune (G1) en relación coninmunoterapia.Plan : se suspende levotiroxina 75 mg/24h vo. Seguimiento.

T4 (0,8-2) ng/dl TSH (0,38-4,84) mU/L

Basal 1 3

Día 15 4.6

- D37:o Hipertiroidismo primario autoinmune en relación con inmunoterapia.

Mejoría analítica espontánea

- D39:- TAP: empeoramiento de las lesiones radiológicas pulmonares y renales (PE)- Metilprednisolona 1,5 mg/kg/d

- D39:o Ptosis bilateral de predominio derecho. No diplopias ni cefaleas.

Fuerza muscular ligeramente disminuida de forma generalizada

o Sospecha diagnóstica: ptosis de probable origen tiroideo versus medicamentoso

- D39:- TAP: empeoramiento de las lesiones radiológicas pulmonares y renales (PE)

- Metilprednisolona 1,5 mg/kg/d

- D44:


Mejoría analítica espontánea- D44

o Exploración: el paciente refiere asteniao JC: ptosis NO relacionada de ningún modo con la alteración tiroideao Plan: reinicio Levotiroxina (Eutirox®) 75 mcg

T4 (0,8-2) ng/dl TSH (0,38-4,84) mU/L

Basal 1 3

Día 15 4.6



- D44:

- D46:

- D39:o Ptosis bilateral de predominio derecho. No diplopías ni cefaleas.



- D46:o Electromiografía: polineuropatía y miopatía grave más posible

afectación de la placa motora con disminución de señal tras la estimulación repetitiva.

o Plan: dada la clínica sugestiva de síndrome miasteniforme

Piridostigmina (Mestinon®) 60 mg/8h

- D46:

o JC: ↑ troponina probablemente relacionado con miositis por inmunoterapia. Sin datos que sugieran isquemia ante la ausencia de clínica y alteraciones ecocardiográficas.

o Plan: solicitar RM cardiaca por sospecha de miocarditis.

Troponina T (0-14ng/L) proBNP (0-125pg/ml) CK(0-190U/l)

Día 29 198 --- 841

Día37 --- --- 2681

Día 46 686 1589 329

- D46:o A la exploración no debilidad y sin problemas para levantarse,

vestirse o caminar.o JD: miositis vs miastenia graviso Plan: mantener corticoides



- D44:

- D46:

- D51:

- Metilprednisolona 1g x 3 días


Mejoría analítica espontánea- D44

o Exploración: el paciente refiere asteniao JC: ptosis NO relacionada de ningún modo con la alteración tiroideao Plan: reinicio Levotiroxina (Eutirox®) 75 mcg

- D51: T4: 0,5 TSH: 63,4

o Plan: ↑ Levotiroxina 125 mcg/d y control en 4 semanas

T4 (0,8-2) ng/dl TSH (0,38-4,84) mU/L

Basal 1 3

Día 15 4.6

- D46:

o JC: ↑ troponina probablemente relacionado con miositis por inmunoterapia. Sin datos que sugieran isquemia ante la ausencia de clínica y alteraciones electrocardiográficas.

o Plan: solicitar RM cardiaca por sospecha de miocarditis

- D51:

o RM: probable edema miocárdico sin fibrosis asociadao JD: muy probable miocarditis en relación con la inmunoterapiao Plan: mantener corticoterapia sin añadir otros inmunosupresores porque

función ventricular no alterada

Troponina T (0-14ng/L) proBNP (0-125pg/ml) CK(0-190U/l)

Día 29 198 --- 841

Día37 --- --- 2681

Día 46 686 1589 329

Troponina T (-14ng/L) proBNP (0-125pg/ml) CK(0-190U/l)

Día 29 198 --- 841

Día37 --- --- 2681

Día 46 686 1589 329

Día 51 1167 367 137



- D51:o Ante elevada sospecha de afectación miocárdica ↑ corticoides 1g de

metilprednisolona x 3 días. Si no mejoría→ Infliximab



- D44:

- D46:

- D51:

- Metilprednisolona 1g x 3 días

- D53: - Prednisona 60 mg/d



- D51:o Ante elevada sospecha de afectación miocárdica ↑ corticoides 1g de

metilprednisolona x 3 días. Si no mejoría→ Infliximab

- D53:o Mejoría progresiva del paciente sin clínica de inflamación muscular,

excepto la disfagia que va mejorando

- D58:- Vómitos en posos de de café con coágulos. Se solicita endoscopia urgente- Prednisona 40 mg/día pauta descendente hasta suspender

- D39:o Ptosis bilateral de predominio derecho. No diplopías ni cefaleas.



- D46:o Electromiografía: polineuropatía y miopatía grave más posible

afectación de la placa motora con disminución de señal tras la estimulación repetitiva.

o Plan: dada la clínica sugestiva de síndrome miasteniforme

Piridostigmina (Mestinon®) 60 mg

- D58:o Mejoría progresiva de la ptosis y la motilidad ocular


- D59:- Endoscopia: úlceras duodenales- JD: toxicidad corticoides vs toxicidad inmunorrelacionada

- D64:- Mala situación clínica con deterioro progresivo por HDA y melenas . Hemorragias

digestivas de repetición con anemización grave con necesidad de soporte transfusional

- D71:

- D71:o Troponina en descenso: 265 (0-14 ng/l)o Plan: ante estabilidad radiológica sin complicaciones clínicas se

finaliza seguimiento del paciente.


- D59:- Endoscopia: úlceras duodenales- JD: toxicidad corticoides vs toxicidad inmunorrelacionada

- D64:- Mala situación clínica con deterioro progresivo por HDA y melenas . Hemorragias

digestivas de repetición con anemización grave con necesidad de soporte transfusional

- D71:

- D79: EXITUS

Table 7. Management of Nervous System irAEs in Patients Treated With ICPis

7.0 Nervous System Toxicities

7.1 Myasthenia gravisDefinition: Fatigable or fluctuating muscle weakness, generally more proximal than distal. Frequently has ocular and/or bulbar involvement (ptosis, extraocular

movement abnormalities resulting in double vision, dysphagia, dysarthria, facial muscle weakness). May have neck and/or respiratory muscle weakness. (Note:May occur with myositis and/or myocarditis. Respiratory symptomsmay require evaluation to rule out pneumonitis, myocarditis. Miller Fisher variant of Guillain-Barré syndrome (ophthalmoparesis) and the oculobulbar myositis (ptosis, ophthalmoparesis, dysphagia, neck and respiratory weakness) with ICPi may haveoverlapping symptoms.

Diagnostic work-upAChR and antistriated muscle antibodies in blood; if AChR antibodies are negative, consider muscle specific kinase and lipoprotein-related 4 antibodies in bloodPulmonary function assessment with NIF and VCCPK, aldolase, ESR, CRP for possible concurrent myositisConsider MRI of brain and/or spine, depending on symptoms to rule out CNS involvement by disease or alternate diagnosisIf respiratory insufficiency or elevated CPK, troponin T, perform cardiac examination with ECG and TTE for possible concomitant myocarditisNeurologic consultationElectrodiagnositic studies, including neuromuscular junction testing with repetitive stimulation and/or jitter studies, NCS to exclude neuropathy, and needle EMG to

evaluate for myositis

Grading Management

All grades All grades warrant work-up and intervention given potential for progressivemyasthenia gravis to lead to respiratory compromise

No G1G2: Some symptoms interfering with ADLMGFA severity class

1 (ocular symptoms and findings only) and MGFAseverity class 2 (mild generalized weakness)

Hold ICPi and may resume in G2 patients (MGFA 1 and 2) only if symptoms resolve87

Should consult neurologyPyridostigmine starting at 30 mg orally three times a day and gradually increase tomaximum of 120 mg orally four times a day as tolerated and based on symptomsAdminister corticosteroids (prednisone, 1-1.5 mg/kg orally daily) if symptoms G2;wean based on symptom improvement

G3-4: Limiting self-care and aids warranted, weakness limitingwalking, ANY dysphagia, facial weakness, respiratorymuscle weakness, or rapidly progressive symptoms, orMGFA severity class 3-4moderate to severe generalizedweakness to myasthenic crisis

Permanently discontinue ICPiAdmit patient, may need ICU-level monitoringNeurology consultContinue corticosteroids and initiate IVIG 2 g/kg IV over 5 days (0.4 g/kg/d) orplasmapheresis for 5 daysFrequent pulmonary function assessmentDaily neurologic review

Additional considerationsAvoid medications that can worsen myasthenia: b-blockers, IV magnesium, fluoroquinolones, aminoglycosides, and macrolidesInitially a 5-day course of plasmapheresis or a 2 g/kg course of IVIG over 5 days1-2 mg/kg methylprednisolone daily, wean based on symptom improvementPyridostigmine, wean based on improvementICPi-associated myasthenia gravis may be monophasic, and additional corticosteroid-sparing agents may not be required

7.2 Guillain-Barré syndromeDefinition: Progressive, most often symmetrical muscle weakness with absent or reduced deep tendon reflexes. Often starts with sensory symptoms/neuropathic

pain localized to lower back and thighs. May involve extremities (typically ascending weakness but not always), facial, respiratory, and bulbar and oculomotornerves. May have dysregulation of autonomic nerves.

Diagnostic work-upNeurologic consultationMRI of spine with or without contrast (rule out compressive lesion and evaluate for nerve root enhancement/thickening)Lumbar puncture: CSF typically has elevated protein and often elevated WBCs; even though this is not typically seen in classic Guillain-Barré syndrome, cytology

should be sent with any CSF sample from a patient with cancer.Serum antiganglioside antibody tests for Guillain-Barré syndrome and its subtypes (eg, anti-GQ1b forMiller Fisher variant associatedwith ataxia and ophthalmoplegia)Electrodiagnostic studies to evaluate polyneuropathyPulmonary function testing (NIF/VC)Frequent neurochecks

Grading Management

All grades Warrant work-up and intervention given potential for progressive Guillain-Barrésyndrome to lead to respiratory compromiseNote: There is no G1 toxicity

G1: Mild, none NAG2: Moderate, some interference with ADL, symptoms

concerning to patientG3-4: Severe, limiting self-care and aids warranted, weakness

limiting walking, ANY dysphagia, facial weakness,respiratory muscle weakness, or rapidly progressivesymptoms

Discontinue ICPiAdmission to inpatient unit with capability of rapid transfer to ICU-level monitoringStart IVIG (0.4 g/kg/d for 5 days for a total dose of 2 g/kg) or plasmapheresis.Corticosteroids are usually not recommended for idiopathic Guillain-Barrésyndrome; however, in ICPi-related forms, a trial is reasonable (methylprednisolone2-4 mg/kg/d), followed by slow corticosteroid taperPulse corticosteroid dosing (methylprednisolone 1 g/d for 5 days) may also beconsidered for G3-4 along with IVIG or plasmapheresisFrequent neurochecks and pulmonary function monitoringMonitor for concurrent autonomic dysfunctionNonopioid management of neuropathic painTreatment of constipation/ileus

(continued on following page)

1744 © 2018 American Society of Clinical Oncology and National Comprehensive Cancer Network JOURNAL OF CLINICAL ONCOLOGY

Brahmer et al

Downloaded from ascopubs.org by 83.54.170.67 on July 13, 2018 from 083.054.170.067Copyright © 2018 American Society of Clinical Oncology. All rights reserved.

Brahmeretal.Managementofimmune-relatedadverseeventsinpatientstreatedwithimmunecheckpointinhibitortherapy.JClinOncol.2018.Feb1410

Ø Incidencia de efectos adversos neurológicos: 1%Ø Tiempo hasta comienzo: 6-13 semanasØ Polineuropatía, parálisis facial, desmielinización, miastenia gravis,

síndrome Guillain Barré, leucoencefalopatía posterior reversible, mielitis transversa, encefalitis, meningitis aséptica

Ø Tanto hipo como hipertiroidismo se han descrito, aunque hipotiroidismomás frecuente

Ø Hipertiroidismo suele ser transitorio y preceder a hipotiroidismoØ Monoterapia con anti PD-1/PD-L1: 5-10%

Table 4. Management of Endocrine irAEs in Patients Treated With ICPis

4.0 Endocrine Toxicity

Counsel patients to inform their health care provider immediately if they experience any changes in their health since their last visit, especially any of the following:Headaches that will not go away or unusual headache patternsVision changesRapid heartbeatIncreased sweatingExtreme tiredness or weaknessMuscle achesWeight gain or weight lossDizziness or faintingFeeling more hungry or thirsty than usualHair lossChanges in mood or behavior, such as decreased sex drive, irritability, or forgetfulnessFeeling coldConstipationVoice gets deeperUrinating more often than usualNausea or vomitingAbdominal pain

4.1 Thyroid4.1.1 Primary hypothyroidismDefinition: Elevated TSH, normal or low FT4Diagnostic work-upTSH and FT4 every 4-6 weeks as part of routine clinical monitoring on therapy or for case detection in symptomatic patients

Grading Management

G1: TSH , 10 mIU/L and asymptomatic Should continue ICPi with close follow-up and monitoring of TSH, FT4G2: Moderate symptoms; able to perform ADL; TSH

persistently . 10 mIU/LMay hold ICPi until symptoms resolve to baselineConsider endocrine consultationPrescribe thyroid hormone supplementation in symptomatic patientswith anydegree of TSH elevation or in asymptomatic patients with TSH levels thatpersist . 10 mIU/L (measured 4 weeks apart)Monitor TSHevery6-8weekswhile titratinghormone replacement tonormalTSHFT4 can be used in the short term (2 weeks) to ensure adequacy of therapy inthose with frank hypothyroidism where the FT4 was initially lowOnce adequately treated, should monitor thyroid function (at least TSH) every 6weeks while on active ICPi therapy or as needed for symptoms to ensureappropriate replacement; repeat testing annually or as indicated by symptomsonce stable

G3-4: Severe symptoms, medically significant or life-threatening consequences, unable to perform ADL

Hold ICPi until symptoms resolve to baseline with appropriatesupplementationEndocrine consultationMay admit for IV therapy if signs of myxedema (bradycardia, hypothermia)Thyroid supplementation and reassessment as in G2

Additional considerationsFor patients without risk factors, full replacement can be estimated with an ideal body weight–based dose of approximately 1.6 mg/kg/dFor elderly or fragile patients with multiple comorbidities, consider titrating up from low dose, starting at 25-50 mgExtreme elevations of TSH can be seen in the recovery phase of thyroiditis and can be watched in asymptomatic patients to determine whether there is recovery to

normal within 3-4 weeksUnder guidance of endocrinology, consider tapering hormone replacement and retesting in patients with a history of thyroiditis (initial thyrotoxic phase)Adrenal dysfunction, if present, must always be replaced before thyroid hormone therapy is initiated

4.1.2 HyperthyroidismDefinition: Suppressed TSH and high normal or elevated FT4 and/or triiodothyronineDiagnostic work-upMonitor TSH, FT4 every 4-6 weeks from the start of therapy or as needed for case detection in symptomatic patientsConsider TSH receptor antibodies if there are clinical features and suspicion of Grave disease (eg, ophthalmopathy)Close monitoring of thyroid function every 2-3 weeks after diagnosis to catch transition to hypothyroidism in patients with thyroiditis and hyperthyroidism

Grading Management

G1: Asymptomatic or mild symptoms Can continue ICPi with close follow-up and monitoring of TSH, FT4 every 2-3weeks until it is clear whether there will be persistent hyperthyroidism (seebelow) or hypothyroidism (see 4.1.1)

G2: Moderate symptoms, able to perform ADL Consider holding ICPi until symptoms return to baselineConsider endocrine consultationb-Blocker (eg, atenolol, propranolol) for symptomatic reliefHydration and supportive careCorticosteroids are not usually required to shorten durationFor persistent hyperthyroidism (. 6 weeks) or clinical suspicion, work-up forGraves disease (TSI or TRAb) and consider thionamide (methimazole or PTU)Refer to endocrinology for Graves disease


jco.org © 2018 American Society of Clinical Oncology and National Comprehensive Cancer Network 1731

Management of Immune-Related Adverse Events



Table 9. Management of Cardiovascular irAEs in Patients Treated With ICPis

9.0 Cardiovascular Toxicities

9.1 Myocarditis, pericarditis, arrhythmias, impaired ventricular function with heart failure and vasculitisDefinition: Signs and symptoms may include chest pain, arrhythmia, palpitations, peripheral edema, progressive or acute dyspnea, pleural effusion, fatigueDiagnostic work-upAt baseline

ECGConsider troponin, especially in patient treated with combination immune therapies

Upon signs/symptoms (consider cardiology consult)ECGTroponinBNPEchocardiogramCXR

Additional testing to be guided by cardiology and may includeStress testCardiac catherizationCardiac MRI

Grading Management

G1: Abnormal cardiac biomarker testing, including abnormalECG

All grades warrant work-up and intervention given potential for cardiaccompromise

G2: Abnormal screening tests with mild symptoms Consider the following:G3: Moderately abnormal testing or symptoms with mild

activityHold ICPi and permanently discontinue after G1

G4: Moderate to severe decompensation, IV medication orintervention required, life-threatening conditions

High-dose corticosteroids (1-2mg/kg of prednisone) initiated rapidly (oral or IVdepending on symptoms)Admit patient, cardiology consultationManagement of cardiac symptoms according to ACC/AHA guidelines andwith guidance from cardiologyImmediate transfer to a coronary care unit for patients with elevatedtroponin or conduction abnormalitiesIn patients without an immediate response to high-dose corticosteroids,consider early institution of cardiac transplant rejection doses ofcorticosteroids (methylprednisolone 1 g every day) and the addition ofeither mycophenolate, infliximab, or antithymocyte globulin

Qualifying statement: Treatment recommendations are based on anecdotal evidence and the life-threatening nature of cardiovascular complications. Holdingcheckpoint inhibitor therapy is recommended for all grades of complications. The appropriateness of rechallenging remains unknown. Note that infliximab hasbeen associated with heart failure and is contraindicated at high doses in patients with moderate-severe heart failure.108

9.2 Venous thromboembolismDefinition: A disorder characterized by occlusion of a vessel by a thrombus that has migrated from a distal site via the blood stream. Clinical signs and symptoms are

variable and may include pain, swelling, increased skin vein visibility, erythema, and cyanosis accompanied by unexplained fever for DVT and dyspnea, pleuriticpain, cough, wheezing, or hemoptysis for PE

Diagnostic work-upEvaluation of signs and symptoms of PE or DVT may include

Clinical prediction rule to stratify patients with suspected venous thromboembolismVenous ultrasound for suspected DVTCTPA for suspected PE

Can also consider D-dimer for low-risk patients based on risk stratification by clinical prediction rule for DVT/PE when CT or Doppler are not available or appropriateVentilation/perfusion scan is also an option when CTPA is not appropriateConsider other testing, including ECG, CXR, BNP and troponin levels, and arterial blood gas

Grading Management

G1: Venous thrombosis (eg, superficial thrombosis) Continue ICPiWarm compressClinical surveillance

G2: Venous thrombosis (eg, uncomplicated DVT), medicalintervention indicated

Continue ICPi

G3: Thrombosis (eg, uncomplicated PE [venous], nonemboliccardiac mural [arterial] thrombus), medical interventionindicated

Management according to CHEST, ACC, and/or AHA guidelines andconsider consult from cardiology or other relevant specialtiesLMWH is suggested over VKA, dabigatran, rivaroxaban apixaban, oredoxaban for initial and long-term treatmentIV heparin is an acceptable alternative for initial use, and oral anticoagulantsare acceptable for the long term

G4: Life-threatening (eg, PE, cerebrovascular event, arterialinsufficiency), hemodynamic or neurologic instability,urgent intervention indicated

Permanently discontinue ICPiAdmit patient and management according to CHEST, ACC, and/or AHAguidelines and with guidance from cardiologyRespiratory and hemodynamic supportLMWH is suggested over VKA, dabigatran, rivaroxaban, apixaban, oredoxaban for initial and long-term treatmentIV heparin is an acceptable alternative for initial use, and oral anticoagulantsare acceptable for the long termFurther clinical management as indicated based on symptoms


jco.org © 2018 American Society of Clinical Oncology and National Comprehensive Cancer Network 1757

Management of Immune-Related Adverse Events



Ø Incidencia < 1% y tiempo de aparición variableØ Pericarditis, hipertensión, arritmias ventriculares,

miocarditisØ Signos y síntomas heterogéneos e inespecíficosØ Marcadores séricos cardiacos (CK y troponina I/T)

elevados, ECG basal normalØ Ecografía a todos los pacientes sintomáticos

NEUROLOGÍA

MEDICINADIGESTIVA

REUMATOLOGÍA

NEUMOLOGÍA

FARMACIA

ENFERMERÍA

CARDIOLOGÍA

INMUNOLOGÍA

RADIODIAGNÓSTICO

HEMATOLOGÍA

ANATOMÍA PATOLÓGICA

ANÁLISIS CLÍNICOS

DERMATOLOGÍA

NEFROLOGÍA

ENDOCRINOLOGÍA

ONCOLOGÍA

Documents

EFECTOS SECUNDARIOS DE LA INMUNOTERAPIA · -D37: o Hipertiroidismo primario autoinmune en relación con inmunoterapia. Mejoría analítica espontánea-D44o Exploración: el paciente