Immune Checkpoint Inhibitor Adverse Event Management — Part 5: Hematologic, Ophthalmologic irAEs, Special Populations, and Rechallenge
Management of immune-mediated hematologic toxicities, ophthalmologic irAEs, combination immunotherapy toxicity profiles, rechallenge criteria, preexisting autoimmune disease, special populations, multidisciplinary triggers, and patient education.
Hematologic Immune-Related Adverse Events
Hematologic irAEs are uncommon (< 1%–3%) but include potentially life-threatening cytopenias. They can be challenging to diagnose because cytopenias in oncology patients have a broad differential including disease progression, chemotherapy effects, and bone marrow infiltration.1 2 3
Immune Thrombocytopenia (ITP)
ICI-associated immune thrombocytopenia presents with isolated thrombocytopenia, often with mucocutaneous bleeding (petechiae, purpura, epistaxis, gingival bleeding). It shares features with primary ITP.
Workup:
- CBC with peripheral blood smear (isolated thrombocytopenia; review smear for schistocytes to exclude TMA/TTP, platelet clumping for pseudothrombocytopenia)
- Reticulocyte count
- Direct antiglobulin test (DAT/Coombs) – rule out concurrent autoimmune hemolytic anemia (Evans syndrome)
- Haptoglobin, LDH, indirect bilirubin – rule out hemolysis
- HIV, HCV serologies
- H. pylori testing
- Coagulation studies (PT, aPTT, fibrinogen) – rule out DIC
- Bone marrow biopsy if diagnosis uncertain or refractory to treatment (typically shows adequate or increased megakaryocytes in ITP)
Grading and Management:
| Grade | Platelet Count | ICI Decision | Management |
|---|---|---|---|
| Grade 1 | 75,000–150,000/mcL | Continue ICI with monitoring | Monitor CBC twice weekly; no treatment needed unless symptomatic |
| Grade 2 | 50,000–75,000/mcL | Hold ICI | Prednisone 1 mg/kg/day; monitor CBC every 2–3 days; hematology consultation; resume ICI once platelets > 75,000 and steroids tapering |
| Grade 3 | 25,000–50,000/mcL | Hold ICI | Prednisone 1–2 mg/kg/day; hematology consultation; if active bleeding or rapid decline: IVIG 1 g/kg IV (may repeat on day 2); platelet transfusion for active hemorrhage (note: limited efficacy in ITP but appropriate for life-threatening bleeding); if steroid-refractory: rituximab (375 mg/m2 weekly x 4), thrombopoietin receptor agonists (eltrombopag 50–75 mg daily or romiplostim 1–10 mcg/kg weekly) |
| Grade 4 | < 25,000/mcL | Permanently discontinue ICI | Pulse methylprednisolone 1 g IV daily x 3 days then prednisone 1–2 mg/kg/day; IVIG 1 g/kg IV x 1–2 doses; hematology consultation (urgent); platelet transfusion for active hemorrhage; rituximab for refractory cases; TPO-RA for refractory cases; aminocaproic acid 1–4 g IV/PO for mucosal bleeding; splenectomy is a last resort |
Autoimmune Hemolytic Anemia (AIHA)
ICI-associated AIHA presents with fatigue, jaundice, dark urine, pallor, and laboratory evidence of hemolysis (elevated LDH, indirect bilirubin, reticulocyte count; decreased haptoglobin; positive DAT).
Workup:
- CBC, reticulocyte count, peripheral smear (spherocytes)
- Direct antiglobulin test (DAT) – positive for IgG and/or complement (C3)
- LDH, haptoglobin, indirect bilirubin (hemolysis markers)
- Cold agglutinin titer (if cold AIHA suspected)
- Rule out concurrent ITP (Evans syndrome)
Management:
| Severity | ICI Decision | Management |
|---|---|---|
| Mild (Hgb 10–12 g/dL, mild hemolysis) | Hold ICI | Prednisone 1 mg/kg/day; folic acid 1 mg daily; monitor hemoglobin and hemolysis markers daily initially; hematology consultation |
| Moderate (Hgb 8–10 g/dL) | Hold ICI | Prednisone 1–2 mg/kg/day; consider IVIG 0.4 g/kg/day x 5 days if rapidly dropping; transfuse if hemodynamically symptomatic (note: cross-matching may be difficult); hematology consultation |
| Severe (Hgb < 8 g/dL, hemodynamic instability) | Permanently discontinue ICI | Pulse methylprednisolone 1 g IV daily x 3 days, then 1–2 mg/kg/day; IVIG; transfuse PRBCs (least incompatible units if cross-match difficult); if refractory: rituximab (375 mg/m2 weekly x 4 or 1000 mg x 2); cyclophosphamide or mycophenolate for refractory cases; splenectomy as last resort |
Aplastic Anemia / Bone Marrow Failure
Aplastic anemia is a rare but potentially fatal hematologic irAE presenting with pancytopenia. It requires bone marrow biopsy for diagnosis, showing hypocellular marrow.
Management:
- Permanently discontinue ICI
- High-dose corticosteroids: methylprednisolone 1–2 mg/kg/day IV
- Hematology consultation (urgent)
- If steroid-refractory: ATG (equine ATG 40 mg/kg/day x 4 days or rabbit ATG 1.5 mg/kg/day x 5 days) + cyclosporine (standard aplastic anemia regimen)
- Eltrombopag may be considered
- Supportive care: transfusion support, growth factors (G-CSF for neutropenia), infection prophylaxis
- Bone marrow transplant evaluation for severe, refractory cases
Acquired Hemophilia A
Acquired hemophilia A (autoantibodies against factor VIII) is a rare but serious hematologic irAE presenting with spontaneous hemorrhage (soft tissue hematomas, mucosal bleeding) and prolonged aPTT with low factor VIII activity and positive Bethesda inhibitor titer.
Management:
- Permanently discontinue ICI
- Hematology consultation (urgent)
- Bypassing agents for bleeding: recombinant factor VIIa (NovoSeven 90 mcg/kg) or activated prothrombin complex concentrate (FEIBA 50–100 units/kg)
- Immunosuppression to eradicate inhibitor: prednisone 1 mg/kg/day + cyclophosphamide 1–2 mg/kg/day (or rituximab 375 mg/m2 weekly x 4)
- Factor VIII concentrate is generally ineffective in the presence of high-titer inhibitor
Ophthalmologic Immune-Related Adverse Events
Ophthalmologic irAEs are uncommon (< 1%–2%) but can threaten vision if not promptly recognized and managed. Ophthalmology consultation should be obtained urgently for any ocular complaints in ICI-treated patients.1 2
Uveitis
The most common ophthalmologic irAE. Can be anterior (iritis), intermediate, posterior, or panuveitis. Presents with eye pain, photophobia, blurred vision, floaters, and conjunctival injection.
| Grade | ICI Decision | Management |
|---|---|---|
| Grade 1 (anterior uveitis, mild, no visual acuity change) | Continue ICI | Urgent ophthalmology referral; topical corticosteroid drops (prednisolone acetate 1% every 1–2 hrs, tapering over weeks); cycloplegic drops (cyclopentolate or atropine) for pain and to prevent synechiae |
| Grade 2 (moderate, mild visual acuity reduction) | Hold ICI | Ophthalmology consultation; topical corticosteroid drops; periocular or intravitreal corticosteroid injection for posterior uveitis; consider prednisone 0.5–1 mg/kg/day for bilateral or posterior uveitis not responding to topical therapy |
| Grade 3–4 (severe, visual acuity 20/200 or worse, retinal detachment) | Hold or permanently discontinue ICI | Urgent ophthalmology; systemic corticosteroids (prednisone 1–2 mg/kg/day); intravitreal corticosteroid injection; if steroid-refractory: mycophenolate, methotrexate, or adalimumab per ophthalmology guidance; permanent discontinuation if severe or recurrent |
Episcleritis / Scleritis
Presents with eye redness, pain, and tearing. Scleritis is more severe and may be associated with scleral thinning and vision loss.
- Episcleritis: Typically mild; manage with artificial tears and topical NSAIDs (ketorolac drops); continue ICI; ophthalmology referral
- Scleritis: More serious; hold ICI; ophthalmology consultation; systemic NSAIDs or prednisone 0.5–1 mg/kg/day; immunosuppressive agents for refractory cases
Orbital Inflammation / Graves-Like Orbitopathy
Proptosis, periorbital edema, diplopia, and extraocular movement restriction can occur, sometimes in association with thyroid irAEs. Manage with systemic corticosteroids and ophthalmology consultation; consider teprotumumab or orbital radiation for refractory cases.
Retinal irAEs
Rare but sight-threatening irAEs including Vogt-Koyanagi-Harada-like syndrome (bilateral panuveitis with exudative retinal detachment, vitiligo, poliosis) and serous retinal detachment. Require aggressive systemic immunosuppression and subspecialty co-management.
Combination Immunotherapy Toxicity Profiles
The combination of anti-CTLA-4 plus anti-PD-1 (most commonly ipilimumab plus nivolumab) is associated with significantly higher rates and severity of irAEs compared to either agent alone.1 3 4
Comparative Incidence of irAEs
| irAE | Anti-PD-1/PD-L1 Monotherapy | Anti-CTLA-4 Monotherapy | Anti-CTLA-4 + Anti-PD-1 Combination |
|---|---|---|---|
| Any irAE (all grades) | 55%–70% | 60%–85% | 80%–95% |
| Grade 3–4 irAE | 10%–15% | 20%–30% | 40%–60% |
| Colitis (all grades) | 1%–3% | 8%–12% | 15%–20% |
| Hepatitis (all grades) | 1%–4% | 5%–10% | 15%–20% |
| Dermatologic (all grades) | 20%–30% | 40%–50% | 40%–60% |
| Thyroid dysfunction | 10%–20% | 1%–5% | 20%–30% |
| Hypophysitis | 0.5%–1% | 5%–10% | 6%–12% |
| Pneumonitis | 2%–5% | 1%–2% | 7%–10% |
| Myocarditis | 0.04%–0.5% | 0.04%–0.2% | 0.3%–1.5% |
| Treatment discontinuation | 5%–10% | 10%–15% | 30%–40% |
Key Differences in Combination Therapy Toxicity
- Earlier onset: irAEs with combination therapy tend to present earlier and more acutely
- Multiple concurrent irAEs: Patients on combination therapy more frequently develop irAEs in multiple organ systems simultaneously, complicating management
- Higher rates of grade 3–4 events: Approximately 40%–60% on combination vs 10%–15% on anti-PD-1 monotherapy
- Colitis and hepatitis are disproportionately more common with combination therapy
- Dose-dependent CTLA-4 toxicity: Ipilimumab at 3 mg/kg (used in melanoma) has higher toxicity rates than at 1 mg/kg (used in RCC, NSCLC)
Management Considerations for Combination Therapy irAEs
- Consider discontinuing anti-CTLA-4 while continuing anti-PD-1 after irAE resolution for grade 2 events
- Permanently discontinue anti-CTLA-4 for any grade 3+ irAE
- Lower threshold for aggressive immunosuppression given higher likelihood of severe and refractory irAEs
- More vigilant monitoring (labs before every cycle, routine troponin monitoring increasingly recommended)
Rechallenge After irAE
Rechallenge with ICI after an irAE is a complex clinical decision that must weigh the potential oncologic benefit against the risk of irAE recurrence and the availability of alternative therapies.1 2 3 5
General Principles
- The overall rate of irAE recurrence upon rechallenge is approximately 30%–50% (same or different organ system)
- Rechallenge with the same class of ICI carries a higher risk of same-organ irAE recurrence
- Switching from anti-CTLA-4 to anti-PD-1 (or vice versa) after an irAE generally has a lower but not negligible risk of recurrence
- Continuing anti-PD-1 monotherapy after discontinuing anti-CTLA-4 due to irAE is a common and generally well-tolerated approach
Contraindications to Rechallenge (Permanent Discontinuation Required)
The following irAEs mandate permanent discontinuation of all ICI therapy with no rechallenge:
- Myocarditis (any grade)
- Stevens-Johnson syndrome or toxic epidermal necrolysis
- Grade 3–4 pneumonitis
- Grade 4 colitis or colitis with perforation
- Grade 4 hepatitis
- Grade 3–4 neurologic irAEs (myasthenia gravis, Guillain-Barre, encephalitis)
- Grade 4 nephritis
- Grade 3–4 myositis with cardiac or respiratory involvement
- Any irAE resulting in organ failure or requiring prolonged immunosuppression
Conditions Allowing Potential Rechallenge
| Prior irAE | Rechallenge Approach |
|---|---|
| Grade 2 dermatologic irAE (resolved) | May rechallenge with same agent; close monitoring |
| Grade 2 colitis (resolved, off steroids) | May rechallenge cautiously; consider anti-PD-1 monotherapy if prior combination; close monitoring with low threshold for re-discontinuation |
| Grade 2 hepatitis (resolved, LFTs normalized) | May rechallenge; monitor LFTs weekly for first 3 cycles |
| Grade 3 colitis or hepatitis (resolved after single course of treatment) | Consider rechallenge only if no alternative therapy; anti-PD-1 monotherapy preferred over combination; extensive shared decision-making; very close monitoring |
| Endocrine irAEs (well controlled on replacement) | May rechallenge; endocrine irAEs generally do not recur (gland already destroyed); continue hormone replacement |
| Grade 2 pneumonitis (fully resolved, imaging clear) | May rechallenge with same agent cautiously; CT chest before each cycle for 3–4 cycles; hold at first sign of recurrence |
| Inflammatory arthritis (mild-moderate, controlled) | May continue ICI with concurrent anti-rheumatic therapy |
| Grade 1–2 nephritis (creatinine returned to baseline) | May rechallenge; monitor creatinine before each cycle |
Rechallenge Protocol
- Confirm complete resolution of the prior irAE (clinical and laboratory)
- Complete corticosteroid taper to < 10 mg/day prednisone (or off steroids entirely)
- Discuss risks and benefits with the patient (informed consent, documentation)
- Consider switching agent class if possible (e.g., from combination to anti-PD-1 monotherapy)
- Increase monitoring frequency:
- Relevant labs before each cycle (e.g., LFTs for prior hepatitis, creatinine for prior nephritis, CBC for prior hematologic irAE)
- Imaging as appropriate (CT chest for prior pneumonitis)
- Lower threshold for holding ICI at first sign of recurrence
- Establish a clear action plan for irAE recurrence before rechallenge begins
- If the irAE recurs (even if milder than the initial episode), strongly consider permanent discontinuation
Preexisting Autoimmune Disease Considerations
Patients with preexisting autoimmune diseases were largely excluded from clinical trials of ICIs. However, real-world evidence demonstrates that ICIs can be used in this population, although with higher rates of both autoimmune flares and de novo irAEs.1 3 5 6
Key Data Points
- Autoimmune flare occurs in approximately 40%–50% of patients with preexisting autoimmune disease treated with ICIs
- De novo irAEs (in a different organ system) occur in approximately 20%–30%
- Most flares are mild to moderate (grade 1–2) and manageable
- Severe flares requiring hospitalization occur in approximately 15%–20%
- ICI discontinuation due to autoimmune flare occurs in approximately 15%–25%
- Despite higher toxicity rates, oncologic responses appear comparable to the general population
Management Recommendations
| Recommendation | Details |
|---|---|
| Multidisciplinary pre-treatment discussion | Involve the relevant autoimmune disease specialist (rheumatologist, dermatologist, gastroenterologist, neurologist) before initiating ICI |
| Optimize baseline autoimmune disease control | Ensure the autoimmune disease is as well-controlled as possible before starting ICI; however, do not delay life-saving cancer treatment excessively for this purpose |
| Avoid anti-CTLA-4 if possible | Anti-PD-1/PD-L1 monotherapy generally has a more favorable toxicity profile in this population; combination therapy carries the highest risk |
| Maintain baseline immunosuppression | Continue existing immunosuppressive medications (low-dose prednisone, DMARDs) during ICI therapy; balance cancer immunity goals with autoimmune control |
| Enhanced monitoring | More frequent lab monitoring and symptom assessment; disease-specific monitoring (e.g., IBD colonoscopy, RA disease activity scores) |
| Low threshold for holding ICI | If autoimmune flare occurs; standard irAE management algorithms apply |
| Specific high-risk conditions | Active CNS demyelinating disease, active myasthenia gravis, and active severe autoimmune hepatitis are generally considered contraindications to ICI therapy due to potentially catastrophic flare risk |
irAEs in Special Populations
Elderly Patients (>/= 65–70 years)
- Overall irAE incidence and severity appear similar to younger patients
- However, elderly patients may have reduced physiologic reserve to tolerate irAEs (particularly myocarditis, severe pneumonitis, and adrenal crisis)
- Higher rates of comorbid conditions (cardiovascular disease, diabetes, renal impairment) complicate management
- Corticosteroid side effects may be more pronounced (hyperglycemia, osteoporosis, delirium, immunosuppression with infection risk)
- Lower starting doses of corticosteroids are NOT recommended – standard weight-based dosing should be used, with attention to supportive care1
Organ Transplant Recipients
ICI therapy in organ transplant recipients carries a high risk (approximately 35%–55%) of allograft rejection, which can lead to graft loss and death. The same T-cell activation that produces antitumor immunity also drives alloimmune responses against the transplanted organ.7
Key considerations:
| Factor | Recommendation |
|---|---|
| Risk of rejection | Approximately 35%–55% experience allograft rejection; kidney transplants have the highest published rates |
| Pre-treatment discussion | Multidisciplinary discussion involving oncology, transplant medicine/surgery, and nephrology (for kidney transplant) |
| Informed consent | Explicit discussion of graft rejection risk, including potential graft loss and need for dialysis or re-transplantation |
| Agent selection | Anti-PD-1/PD-L1 monotherapy preferred over combination; avoid anti-CTLA-4 if possible (may have higher rejection risk) |
| Immunosuppression management | Continue baseline immunosuppression during ICI therapy; some protocols reduce immunosuppression to enhance antitumor immunity, but this increases rejection risk |
| Monitoring | Frequent monitoring of graft function (creatinine for kidney, LFTs for liver, echocardiogram for heart); monitor for rejection signs |
| Rejection management | Standard anti-rejection protocols; ICI discontinuation; high-dose corticosteroids; consider ATG for severe rejection |
Patients with HIV
- ICI therapy appears to be safe and potentially effective in patients with well-controlled HIV (on antiretroviral therapy with CD4 > 200)
- Monitor CD4 count and HIV viral load during ICI therapy
- irAE management follows standard protocols
- Drug interactions between antiretrovirals and immunosuppressive agents (e.g., corticosteroids, mycophenolate) should be reviewed
Multidisciplinary Consultation Triggers
Prompt subspecialty consultation is critical for safe management of irAEs. The following triggers should prompt immediate or urgent consultation:1 2 3
| Subspecialty | Consultation Triggers |
|---|---|
| Gastroenterology | Grade 2 diarrhea/colitis not improving in 3–5 days; any grade 3–4 colitis; need for colonoscopy; suspected CMV colitis; steroid-refractory colitis requiring infliximab/vedolizumab |
| Hepatology | Grade 2 hepatitis not improving in 1 week; grade 3–4 hepatitis; need for liver biopsy; suspected hepatic decompensation (rising bilirubin, INR) |
| Endocrinology | Any hypophysitis; adrenal crisis; new-onset type 1 diabetes or DKA; thyroid storm; complex hormone replacement management |
| Pulmonology | Grade 2 pneumonitis not improving in 48–72 hrs; all grade 3–4 pneumonitis; need for bronchoscopy; uncertain diagnosis |
| Cardiology | Any troponin elevation in ICI patient; suspected myocarditis; new arrhythmia; new heart failure; pericardial effusion; need for cardiac MRI or biopsy |
| Neurology | Any grade 2+ neurologic irAE; suspected myasthenia gravis, GBS, encephalitis, transverse myelitis; need for EMG, lumbar puncture, or brain/spine MRI |
| Nephrology | Grade 2+ creatinine elevation not explained by pre-renal causes; need for renal biopsy; dialysis evaluation |
| Dermatology | Grade 3+ rash; suspected SJS/TEN; bullous disease; need for skin biopsy; refractory dermatitis |
| Rheumatology | Inflammatory arthritis requiring DMARD therapy; myositis; PMR-like syndrome; overlap syndromes; patients with preexisting autoimmune disease |
| Ophthalmology | Any visual symptoms; suspected uveitis, scleritis, or other ocular irAE |
| Hematology | Unexplained cytopenias; suspected ITP, AIHA, or aplastic anemia; acquired hemophilia; need for bone marrow biopsy |
| Intensive Care | Hemodynamic instability; respiratory failure; myasthenic crisis; cardiogenic shock; DKA; adrenal crisis; SJS/TEN |
Patient Education and Monitoring
Proactive patient education is fundamental to early irAE detection and improved outcomes. Patients should be counseled on irAE awareness before initiating ICI therapy and at each treatment visit.1 5
Key Patient Education Points
| Topic | Patient Instruction |
|---|---|
| What are irAEs | The treatment works by activating the immune system against cancer, but the activated immune system can also attack normal tissues. This is different from traditional chemotherapy side effects. |
| Timing | irAEs can occur at any time during treatment and even weeks to months after the last dose. Vigilance should not end when treatment ends. |
| Symptoms requiring urgent contact | New or worsening diarrhea (>/= 4 stools/day above normal); blood in stool; skin rash spreading or blistering; new cough or worsening shortness of breath; persistent headache, visual changes, extreme fatigue; chest pain, palpitations, swelling of legs; new weakness in arms or legs, drooping eyelids, difficulty swallowing; yellowing of eyes or skin; decreased urine output or dark urine; severe abdominal pain |
| Symptoms requiring same-day contact | New rash; mild increase in diarrhea; fatigue that is worsening; new joint pain or swelling; mouth sores; eye redness or pain; numbness or tingling; mild headache |
| Do not self-treat | Patients should not take over-the-counter anti-diarrheal agents without consulting the care team; loperamide is generally appropriate for grade 1 diarrhea but should be avoided if colitis is suspected |
| Corticosteroid education | If started on corticosteroids: take as directed; do not stop abruptly; report side effects (insomnia, mood changes, high blood sugar); take with food; PJP prophylaxis compliance |
| Medical alert | Patients on chronic corticosteroids or hormone replacement (hydrocortisone for adrenal insufficiency) should wear medical alert identification and carry emergency instructions |
| Inform all providers | Patients should inform all healthcare providers (emergency department, dentists, surgeons) that they are on or have recently received immunotherapy and may be on immunosuppressive therapy |
| Vaccination | Live vaccines should be avoided during ICI therapy and while on immunosuppressive treatment for irAEs; inactivated vaccines (influenza, COVID-19) are generally recommended |
Monitoring Schedule Summary
| Timeframe | Monitoring |
|---|---|
| Before each ICI cycle | CMP (LFTs, creatinine), CBC, TSH (every 4–6 weeks), glucose, symptom assessment, review of systems for irAE symptoms |
| During corticosteroid treatment | Glucose (at least weekly, more often if > 40 mg/day); blood pressure; signs of infection; mood assessment; electrolytes |
| After ICI discontinuation | Continue monitoring for at least 6–12 months: TSH every 6–8 weeks, LFTs, creatinine, symptom assessment at each visit; patients should be aware that irAEs can present de novo after treatment ends |
| After irAE resolution | Organ-specific monitoring: repeat labs relevant to prior irAE before rechallenge and at each subsequent cycle; imaging as indicated |
| Lifelong (for permanent endocrine irAEs) | Annual endocrinology follow-up for patients on thyroid or adrenal hormone replacement; stress-dose steroid education reinforcement |
Summary of irAEs Mandating Permanent ICI Discontinuation
The following table consolidates all irAEs requiring permanent discontinuation across organ systems for quick reference:
| irAE | Discontinuation Criteria |
|---|---|
| Myocarditis | Any grade |
| SJS / TEN | Any grade |
| Grade 3–4 pneumonitis | Grade 3 (strongly recommended); Grade 4 (mandatory) |
| Grade 4 colitis or colitis with perforation | Mandatory |
| Grade 4 hepatitis | Mandatory |
| Grade 3–4 myasthenia gravis | Mandatory |
| Grade 3–4 Guillain-Barre syndrome | Mandatory |
| Grade 3–4 encephalitis | Mandatory |
| Grade 3–4 transverse myelitis | Mandatory |
| Grade 4 nephritis | Mandatory |
| Grade 3–4 myositis with cardiac/respiratory involvement | Mandatory |
| Aplastic anemia | Mandatory |
| Any grade 4 irAE | Mandatory (exception: endocrine irAEs manageable on hormone replacement) |
| Any grade 3 irAE not resolving to grade 1 within 12 weeks | Mandatory |
| Inability to taper corticosteroids to < 10 mg/day within 12 weeks | Mandatory |
| Recurrence of same grade 3 irAE upon rechallenge | Mandatory |
References
Schneider BJ, Naidoo J, Santomasso BD, et al. Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology (ASCO) clinical practice guideline update. J Clin Oncol. 2021;39(36):4073-4126. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Haanen J, Obeid M, Spain L, et al. Management of toxicities from immunotherapy: European Society for Medical Oncology (ESMO) clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2022;33(12):1217-1238. ↩︎ ↩︎ ↩︎ ↩︎
Thompson JA, Schneider BJ, Brahmer J, et al. Management of immunotherapy-related toxicities, version 1.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2022;20(4):387-405. ↩︎ ↩︎ ↩︎ ↩︎ ↩︎
Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med. 2018;378(2):158-168. ↩︎
Puzanov I, Diab A, Abdallah K, et al. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer. 2017;5(1):95. ↩︎ ↩︎ ↩︎
Abdel-Wahab N, Shah M, Lopez-Olivo MA, et al. Use of immune checkpoint inhibitors in the treatment of patients with cancer and preexisting autoimmune disease: a systematic review. Ann Intern Med. 2018;168(2):121-130. ↩︎
Fisher J, Zeitouni N, Fan W, Samie FH. Immune checkpoint inhibitor therapy in solid organ transplant recipients: a patient-centered systematic review. J Am Acad Dermatol. 2020;82(6):1490-1500. ↩︎