Immune Checkpoint Inhibitor–Related Pneumonitis Evaluation, Management, and Rechallenge

ICI rechallenge after immune-mediated pneumonitis requires an individualized multidisciplinary risk–benefit assessment. Rechallenge is not an automatic consequence of clinical improvement or radiographic recovery. Potential eligibility Consider rechallenge primarily in appropriately selected patients with previous Grade 1–2 pneumonitis. For Grade 2 pneumonitis, complete clinical symptom resolution is recommended before ICI resumption. Assess whether chest CT abnormalities have improved or resolved and oxygen requirements have returned to baseline. Ideally, systemic corticosteroids should have been discontinued before rechallenge. If treatment resumption during a low-dose corticosteroid taper is considered, follow agent-specific recommendations and multidisciplinary judgment. Pulmonary risk assessment Evaluate: Previous pneumonitis grade and severity. Requirement for hospitalization or supplemental oxygen. Persistent respiratory symptoms or residual radiographic abnormalities. Recurrence during corticosteroid taper. Previous steroid-refractory disease or additional immunosuppression. Pre-existing interstitial lung disease or COPD. Prior thoracic radiotherapy. ICI class and planned treatment regimen. Oncologic risk–benefit assessment Consider: Current cancer status. Previous response and clinical benefit from ICI. Expected benefit of continued immunotherapy. Availability and efficacy of alternative anticancer treatments. Patient preferences and goals of care. Risk of recurrent pneumonitis Discuss the possibility of recurrent immune-mediated pneumonitis, which may be severe or life-threatening. Document the multidisciplinary assessment, anticipated benefit, potential risks, and patient-informed decision. Important restriction ASCO recommends permanent ICI discontinuation after Grade 3–4 immune-mediated pneumonitis. Grade 4 pneumonitis should not be routinely rechallenged. Recovery after severe pneumonitis does not automatically reverse the recommendation for permanent ICI discontinuation. Decision Yes — Rechallenge appropriate: Proceed to "Resume ICI with close monitoring". No — Rechallenge inappropriate: Proceed to "Permanently discontinue ICI or do not rechallenge".

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.

Begin a gradual corticosteroid taper after sustained clinical improvement and stabilization of respiratory status. A typical taper extends over at least 4–6 weeks. Severe, recurrent, or prolonged pneumonitis may require a longer individualized course. Taper planning Document: Corticosteroid agent and prescribed dose. Starting date of the taper. Planned dose reductions. Dates for clinical reassessment. Respiratory symptoms and monitoring parameters. Instructions for recurrence or clinical deterioration. There is no universally appropriate fixed tapering schedule for every patient. Clinical monitoring Monitor: Cough, dyspnea, and respiratory symptoms. Resting oxygen saturation and supplemental oxygen requirements. Functional capacity and exercise tolerance. Chest CT evolution when clinically indicated. Pulmonary function, including DLCO, when useful after stabilization. Corticosteroid safety Monitor for hyperglycemia, hypertension, infection, mood and sleep changes, muscle weakness, and bone-related complications. Assess the need for Pneumocystis jirovecii pneumonia prophylaxis in patients receiving prolonged high-dose corticosteroids according to institutional guidance. Avoid abrupt corticosteroid discontinuation after prolonged systemic exposure. Recurrence during taper New or worsening respiratory symptoms require reassessment for recurrent ICI pneumonitis, infection, and alternative pulmonary diagnoses. Pause further dose reduction pending appropriate clinical evaluation. Reassess pneumonitis severity and the need for treatment escalation. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. Continued improvement Proceed to confirmation of clinical and radiographic recovery, while maintaining the appropriate pulmonary follow-up and ICI discontinuation or rechallenge restrictions.

Initiate urgent multidisciplinary reassessment for severe ICI-related pneumonitis that does not improve adequately after high-dose systemic corticosteroids, usually assessed after approximately 48–72 hours, or earlier in patients with life-threatening respiratory deterioration. Confirm steroid-refractory disease Review the initial diagnosis and clinical trajectory. Confirm the corticosteroid agent, dose, route, and duration. Assess oxygen requirements and the need for ventilatory support. Review radiographic progression and clinical complications. Exclude inadequate treatment exposure or an alternative explanation for deterioration. Reassess infection and alternative diagnoses Investigate possible concurrent infection, including bacterial, viral, fungal, and opportunistic pathogens such as Pneumocystis jirovecii. Consider pulmonary embolism, pulmonary edema, tumor progression, radiation injury, other drug-induced ILD, and diffuse alveolar hemorrhage. Repeat chest CT or consider bronchoscopy with BAL when diagnostically useful and clinically safe. Specialist-directed second-line treatment There is no established superior rescue regimen for steroid-refractory ICI pneumonitis. Potential treatment options include: Mycophenolate mofetil: commonly 1–1.5 g twice daily, with route and duration individualized under specialist supervision. Intravenous immunoglobulin (IVIG): total dose 2 g/kg divided over 2–5 days, according to institutional protocols. Infliximab: 5 mg/kg intravenously in selected cases, after careful assessment of serious infection risk and contraindications. Cyclophosphamide or tocilizumab: selected circumstances under experienced specialist supervision. These options are not interchangeable treatments and should not be routinely combined. Evidence limitations and safety The evidence supporting second-line immunosuppression is limited, largely retrospective, and of low certainty. Published outcomes with infliximab in severe steroid-refractory pneumonitis have been inconsistent, including substantial mortality and infection-related complications in small observational cohorts. Treatment selection must consider infection risk, organ function, concomitant immune-related adverse events, and institutional expertise. Multidisciplinary management Involve pulmonology, oncology, infectious diseases, and critical care as appropriate. Maintain oxygen and respiratory support, infection management, and close clinical reassessment. Do not directly extrapolate the biologic treatment strategy used for ICI-related colitis to pneumonitis.

ICI rechallenge after immune-mediated pneumonitis requires an individualized multidisciplinary risk–benefit assessment. Rechallenge is not an automatic consequence of clinical improvement or radiographic recovery. Potential eligibility Consider rechallenge primarily in appropriately selected patients with previous Grade 1–2 pneumonitis. For Grade 2 pneumonitis, complete clinical symptom resolution is recommended before ICI resumption. Assess whether chest CT abnormalities have improved or resolved and oxygen requirements have returned to baseline. Ideally, systemic corticosteroids should have been discontinued before rechallenge. If treatment resumption during a low-dose corticosteroid taper is considered, follow agent-specific recommendations and multidisciplinary judgment. Pulmonary risk assessment Evaluate: Previous pneumonitis grade and severity. Requirement for hospitalization or supplemental oxygen. Persistent respiratory symptoms or residual radiographic abnormalities. Recurrence during corticosteroid taper. Previous steroid-refractory disease or additional immunosuppression. Pre-existing interstitial lung disease or COPD. Prior thoracic radiotherapy. ICI class and planned treatment regimen. Oncologic risk–benefit assessment Consider: Current cancer status. Previous response and clinical benefit from ICI. Expected benefit of continued immunotherapy. Availability and efficacy of alternative anticancer treatments. Patient preferences and goals of care. Risk of recurrent pneumonitis Discuss the possibility of recurrent immune-mediated pneumonitis, which may be severe or life-threatening. Document the multidisciplinary assessment, anticipated benefit, potential risks, and patient-informed decision. Important restriction ASCO recommends permanent ICI discontinuation after Grade 3–4 immune-mediated pneumonitis. Grade 4 pneumonitis should not be routinely rechallenged. Recovery after severe pneumonitis does not automatically reverse the recommendation for permanent ICI discontinuation. Decision Yes — Rechallenge appropriate: Proceed to "Resume ICI with close monitoring". No — Rechallenge inappropriate: Proceed to "Permanently discontinue ICI or do not rechallenge".

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.

Begin a gradual corticosteroid taper after sustained clinical improvement and stabilization of respiratory status. A typical taper extends over at least 4–6 weeks. Severe, recurrent, or prolonged pneumonitis may require a longer individualized course. Taper planning Document: Corticosteroid agent and prescribed dose. Starting date of the taper. Planned dose reductions. Dates for clinical reassessment. Respiratory symptoms and monitoring parameters. Instructions for recurrence or clinical deterioration. There is no universally appropriate fixed tapering schedule for every patient. Clinical monitoring Monitor: Cough, dyspnea, and respiratory symptoms. Resting oxygen saturation and supplemental oxygen requirements. Functional capacity and exercise tolerance. Chest CT evolution when clinically indicated. Pulmonary function, including DLCO, when useful after stabilization. Corticosteroid safety Monitor for hyperglycemia, hypertension, infection, mood and sleep changes, muscle weakness, and bone-related complications. Assess the need for Pneumocystis jirovecii pneumonia prophylaxis in patients receiving prolonged high-dose corticosteroids according to institutional guidance. Avoid abrupt corticosteroid discontinuation after prolonged systemic exposure. Recurrence during taper New or worsening respiratory symptoms require reassessment for recurrent ICI pneumonitis, infection, and alternative pulmonary diagnoses. Pause further dose reduction pending appropriate clinical evaluation. Reassess pneumonitis severity and the need for treatment escalation. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. Continued improvement Proceed to confirmation of clinical and radiographic recovery, while maintaining the appropriate pulmonary follow-up and ICI discontinuation or rechallenge restrictions.

Continue active multidisciplinary management for severe ICI-related pneumonitis with inadequate response to second-line treatment, or clinically significant recurrence requiring specialized reassessment. This node represents continued active care, not observation alone or automatic cessation of pulmonary treatment. Ongoing respiratory management Maintain hospital-based monitoring and respiratory support according to severity. Reassess oxygenation, ventilatory requirements, respiratory effort, and hemodynamic stability. Review chest imaging and pulmonary complications. Monitor corticosteroid toxicity and adverse effects of additional immunosuppressive medications. Involve critical care when respiratory failure progresses. Diagnostic reassessment Reconsider the initial diagnosis and the possibility of concurrent infection. Evaluate: Bacterial, viral, and fungal pneumonia. Pneumocystis jirovecii and other opportunistic infections. Pulmonary embolism. Radiation pneumonitis or another drug-related pulmonary toxicity. Tumor progression or lymphangitic carcinomatosis. Pulmonary edema. Diffuse alveolar hemorrhage. Other interstitial lung diseases. Repeat chest CT and consider bronchoscopy with BAL or other targeted investigations when clinically useful and safe. Further specialist treatment An experienced multidisciplinary team should determine whether additional immunomodulatory treatment, modification of the current regimen, antimicrobial treatment, or enhanced respiratory support is appropriate. There is no validated automatic third-line rescue sequence. Avoid indiscriminate combination immunosuppression when active infection or another competing diagnosis has not been adequately assessed. Recurrence during corticosteroid taper Confirm whether worsening symptoms represent recurrent immune-mediated pneumonitis, infection, or another pulmonary disorder. Reassess clinical severity and return to the appropriate severity-directed treatment pathway when necessary. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. ICI disposition Previous Grade 3–4 ICI pneumonitis remains an indication for permanent ICI discontinuation under ASCO pneumonitis-specific guidance, regardless of subsequent pulmonary improvement. Continue pulmonary treatment, appropriate rehabilitation, supportive care, and individualized goals-of-care discussions when indicated.

ICI rechallenge after immune-mediated pneumonitis requires an individualized multidisciplinary risk–benefit assessment. Rechallenge is not an automatic consequence of clinical improvement or radiographic recovery. Potential eligibility Consider rechallenge primarily in appropriately selected patients with previous Grade 1–2 pneumonitis. For Grade 2 pneumonitis, complete clinical symptom resolution is recommended before ICI resumption. Assess whether chest CT abnormalities have improved or resolved and oxygen requirements have returned to baseline. Ideally, systemic corticosteroids should have been discontinued before rechallenge. If treatment resumption during a low-dose corticosteroid taper is considered, follow agent-specific recommendations and multidisciplinary judgment. Pulmonary risk assessment Evaluate: Previous pneumonitis grade and severity. Requirement for hospitalization or supplemental oxygen. Persistent respiratory symptoms or residual radiographic abnormalities. Recurrence during corticosteroid taper. Previous steroid-refractory disease or additional immunosuppression. Pre-existing interstitial lung disease or COPD. Prior thoracic radiotherapy. ICI class and planned treatment regimen. Oncologic risk–benefit assessment Consider: Current cancer status. Previous response and clinical benefit from ICI. Expected benefit of continued immunotherapy. Availability and efficacy of alternative anticancer treatments. Patient preferences and goals of care. Risk of recurrent pneumonitis Discuss the possibility of recurrent immune-mediated pneumonitis, which may be severe or life-threatening. Document the multidisciplinary assessment, anticipated benefit, potential risks, and patient-informed decision. Important restriction ASCO recommends permanent ICI discontinuation after Grade 3–4 immune-mediated pneumonitis. Grade 4 pneumonitis should not be routinely rechallenged. Recovery after severe pneumonitis does not automatically reverse the recommendation for permanent ICI discontinuation. Decision Yes — Rechallenge appropriate: Proceed to "Resume ICI with close monitoring". No — Rechallenge inappropriate: Proceed to "Permanently discontinue ICI or do not rechallenge".

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.

Begin a gradual corticosteroid taper after sustained clinical improvement and stabilization of respiratory status. A typical taper extends over at least 4–6 weeks. Severe, recurrent, or prolonged pneumonitis may require a longer individualized course. Taper planning Document: Corticosteroid agent and prescribed dose. Starting date of the taper. Planned dose reductions. Dates for clinical reassessment. Respiratory symptoms and monitoring parameters. Instructions for recurrence or clinical deterioration. There is no universally appropriate fixed tapering schedule for every patient. Clinical monitoring Monitor: Cough, dyspnea, and respiratory symptoms. Resting oxygen saturation and supplemental oxygen requirements. Functional capacity and exercise tolerance. Chest CT evolution when clinically indicated. Pulmonary function, including DLCO, when useful after stabilization. Corticosteroid safety Monitor for hyperglycemia, hypertension, infection, mood and sleep changes, muscle weakness, and bone-related complications. Assess the need for Pneumocystis jirovecii pneumonia prophylaxis in patients receiving prolonged high-dose corticosteroids according to institutional guidance. Avoid abrupt corticosteroid discontinuation after prolonged systemic exposure. Recurrence during taper New or worsening respiratory symptoms require reassessment for recurrent ICI pneumonitis, infection, and alternative pulmonary diagnoses. Pause further dose reduction pending appropriate clinical evaluation. Reassess pneumonitis severity and the need for treatment escalation. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. Continued improvement Proceed to confirmation of clinical and radiographic recovery, while maintaining the appropriate pulmonary follow-up and ICI discontinuation or rechallenge restrictions.

Continue active multidisciplinary management for severe ICI-related pneumonitis with inadequate response to second-line treatment, or clinically significant recurrence requiring specialized reassessment. This node represents continued active care, not observation alone or automatic cessation of pulmonary treatment. Ongoing respiratory management Maintain hospital-based monitoring and respiratory support according to severity. Reassess oxygenation, ventilatory requirements, respiratory effort, and hemodynamic stability. Review chest imaging and pulmonary complications. Monitor corticosteroid toxicity and adverse effects of additional immunosuppressive medications. Involve critical care when respiratory failure progresses. Diagnostic reassessment Reconsider the initial diagnosis and the possibility of concurrent infection. Evaluate: Bacterial, viral, and fungal pneumonia. Pneumocystis jirovecii and other opportunistic infections. Pulmonary embolism. Radiation pneumonitis or another drug-related pulmonary toxicity. Tumor progression or lymphangitic carcinomatosis. Pulmonary edema. Diffuse alveolar hemorrhage. Other interstitial lung diseases. Repeat chest CT and consider bronchoscopy with BAL or other targeted investigations when clinically useful and safe. Further specialist treatment An experienced multidisciplinary team should determine whether additional immunomodulatory treatment, modification of the current regimen, antimicrobial treatment, or enhanced respiratory support is appropriate. There is no validated automatic third-line rescue sequence. Avoid indiscriminate combination immunosuppression when active infection or another competing diagnosis has not been adequately assessed. Recurrence during corticosteroid taper Confirm whether worsening symptoms represent recurrent immune-mediated pneumonitis, infection, or another pulmonary disorder. Reassess clinical severity and return to the appropriate severity-directed treatment pathway when necessary. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. ICI disposition Previous Grade 3–4 ICI pneumonitis remains an indication for permanent ICI discontinuation under ASCO pneumonitis-specific guidance, regardless of subsequent pulmonary improvement. Continue pulmonary treatment, appropriate rehabilitation, supportive care, and individualized goals-of-care discussions when indicated.

ICI rechallenge after immune-mediated pneumonitis requires an individualized multidisciplinary risk–benefit assessment. Rechallenge is not an automatic consequence of clinical improvement or radiographic recovery. Potential eligibility Consider rechallenge primarily in appropriately selected patients with previous Grade 1–2 pneumonitis. For Grade 2 pneumonitis, complete clinical symptom resolution is recommended before ICI resumption. Assess whether chest CT abnormalities have improved or resolved and oxygen requirements have returned to baseline. Ideally, systemic corticosteroids should have been discontinued before rechallenge. If treatment resumption during a low-dose corticosteroid taper is considered, follow agent-specific recommendations and multidisciplinary judgment. Pulmonary risk assessment Evaluate: Previous pneumonitis grade and severity. Requirement for hospitalization or supplemental oxygen. Persistent respiratory symptoms or residual radiographic abnormalities. Recurrence during corticosteroid taper. Previous steroid-refractory disease or additional immunosuppression. Pre-existing interstitial lung disease or COPD. Prior thoracic radiotherapy. ICI class and planned treatment regimen. Oncologic risk–benefit assessment Consider: Current cancer status. Previous response and clinical benefit from ICI. Expected benefit of continued immunotherapy. Availability and efficacy of alternative anticancer treatments. Patient preferences and goals of care. Risk of recurrent pneumonitis Discuss the possibility of recurrent immune-mediated pneumonitis, which may be severe or life-threatening. Document the multidisciplinary assessment, anticipated benefit, potential risks, and patient-informed decision. Important restriction ASCO recommends permanent ICI discontinuation after Grade 3–4 immune-mediated pneumonitis. Grade 4 pneumonitis should not be routinely rechallenged. Recovery after severe pneumonitis does not automatically reverse the recommendation for permanent ICI discontinuation. Decision Yes — Rechallenge appropriate: Proceed to "Resume ICI with close monitoring". No — Rechallenge inappropriate: Proceed to "Permanently discontinue ICI or do not rechallenge".

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.

Resume immune checkpoint inhibitor treatment only after an individualized multidisciplinary risk–benefit assessment confirms that rechallenge is appropriate. Before restarting ICI Document: ICI agent and proposed treatment regimen. Previous pneumonitis grade and clinical severity. Evidence of clinical and radiographic recovery. Current respiratory symptoms and baseline oxygen requirements. Current corticosteroid dose and any ongoing immunosuppression. Anticipated oncologic benefit and available alternatives. Patient-informed decision and agreed monitoring plan. Early monitoring after rechallenge Arrange early clinical reassessment following ICI resumption. Assess: New or recurrent cough. Dyspnea at rest or during exertion. Chest discomfort or fever. Oxygen saturation when clinically appropriate. Functional status and exercise tolerance. Any new or increasing oxygen requirement. Review respiratory symptoms before subsequent ICI administrations. Consider chest CT when symptoms recur or when clinically indicated by previous pneumonitis severity and pulmonary risk. Patient education Provide clear instructions for promptly reporting new respiratory symptoms. Explain that recurrent pneumonitis may require ICI interruption, corticosteroids, hospitalization, or permanent treatment discontinuation. Ensure the patient knows how to contact the oncology team and when urgent medical assessment is required. If pneumonitis recurs Hold ICI and restart diagnostic assessment and severity grading. Reassess infection and other potential pulmonary causes. Determine whether further immunotherapy remains appropriate based on recurrence severity and the expected oncologic benefit. Important treatment principle ICI dose reduction is not an established strategy for preventing recurrence of immune-mediated pneumonitis. Do not reduce the ICI dose empirically as an alternative to appropriate interruption or discontinuation. Ongoing follow-up Maintain communication between oncology and pulmonology. Continue appropriate monitoring for recurrent pneumonitis and persistent pulmonary impairment.

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.

Confirm sustained clinical and radiographic recovery following treatment of ICI-related pneumonitis. Recovery assessment is necessary regardless of whether ICI will be resumed or permanently discontinued. Clinical recovery Assess: Resolution or substantial improvement of cough and dyspnea. Improvement in respiratory effort. Return of oxygen requirements toward baseline. Recovery of functional capacity and activity tolerance. Absence of new respiratory deterioration. Symptoms should ideally return to baseline or Grade 1 before considering possible ICI resumption. Radiographic recovery Review follow-up chest CT for improvement or resolution of inflammatory pulmonary infiltrates. Persistent or progressive abnormalities require further pulmonary assessment, particularly when accompanied by symptoms or oxygen requirements. Additional recovery assessment Document: Current corticosteroid dose and taper schedule. Any ongoing second-line immunosuppressive treatment. Infection status. Residual dyspnea or supplemental oxygen needs. Functional limitations or possible chronic pulmonary impairment. Consider pulmonary function tests, including spirometry and DLCO, when clinically useful. ICI rechallenge eligibility Clinical recovery does not automatically establish eligibility for rechallenge. Patients with previous Grade 3–4 ICI pneumonitis should follow the permanent-discontinuation pathway according to ASCO guidance. Selected patients recovering from Grade 1–2 pneumonitis may proceed to an individualized rechallenge assessment when clinically and oncologically appropriate. Long-term monitoring Arrange appropriate pulmonary follow-up for recurrent symptoms, residual radiographic changes, corticosteroid complications, and late respiratory toxicity. Maintain communication between oncology and pulmonology.

Continue active multidisciplinary management for severe ICI-related pneumonitis with inadequate response to second-line treatment, or clinically significant recurrence requiring specialized reassessment. This node represents continued active care, not observation alone or automatic cessation of pulmonary treatment. Ongoing respiratory management Maintain hospital-based monitoring and respiratory support according to severity. Reassess oxygenation, ventilatory requirements, respiratory effort, and hemodynamic stability. Review chest imaging and pulmonary complications. Monitor corticosteroid toxicity and adverse effects of additional immunosuppressive medications. Involve critical care when respiratory failure progresses. Diagnostic reassessment Reconsider the initial diagnosis and the possibility of concurrent infection. Evaluate: Bacterial, viral, and fungal pneumonia. Pneumocystis jirovecii and other opportunistic infections. Pulmonary embolism. Radiation pneumonitis or another drug-related pulmonary toxicity. Tumor progression or lymphangitic carcinomatosis. Pulmonary edema. Diffuse alveolar hemorrhage. Other interstitial lung diseases. Repeat chest CT and consider bronchoscopy with BAL or other targeted investigations when clinically useful and safe. Further specialist treatment An experienced multidisciplinary team should determine whether additional immunomodulatory treatment, modification of the current regimen, antimicrobial treatment, or enhanced respiratory support is appropriate. There is no validated automatic third-line rescue sequence. Avoid indiscriminate combination immunosuppression when active infection or another competing diagnosis has not been adequately assessed. Recurrence during corticosteroid taper Confirm whether worsening symptoms represent recurrent immune-mediated pneumonitis, infection, or another pulmonary disorder. Reassess clinical severity and return to the appropriate severity-directed treatment pathway when necessary. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. ICI disposition Previous Grade 3–4 ICI pneumonitis remains an indication for permanent ICI discontinuation under ASCO pneumonitis-specific guidance, regardless of subsequent pulmonary improvement. Continue pulmonary treatment, appropriate rehabilitation, supportive care, and individualized goals-of-care discussions when indicated.

Evaluate treatment response only in patients who have actually received second-line immunosuppressive or immunomodulatory therapy for steroid-refractory ICI pneumonitis. Document treatment exposure Record: Selected second-line agent. Dose, route, and administration dates. Concomitant corticosteroid treatment. Baseline respiratory severity. Oxygen and ventilatory support requirements before rescue treatment. Clinical response assessment Monitor: Respiratory symptoms and work of breathing. Oxygen saturation and supplemental oxygen requirements. Need for noninvasive or invasive respiratory support. Respiratory rate and hemodynamic stability. Functional recovery and overall clinical trajectory. Infectious and treatment-related complications. Repeat chest imaging when clinically indicated. Radiographic improvement may lag behind clinical improvement. Yes — Improving Continue appropriate specialist-directed treatment. Once respiratory improvement is sustained and the patient is clinically stable, initiate an individualized corticosteroid taper. Proceed to "Taper corticosteroids and monitor". Recovery must subsequently be confirmed clinically and radiographically. Improvement after rescue treatment does not establish eligibility for ICI rechallenge. No — Persistent or worsening disease Continue urgent specialist-directed pulmonary care. Reassess infection, diagnosis, treatment exposure, and complications. Maintain appropriate respiratory support and consider further individualized treatment under multidisciplinary supervision. Proceed to "Continue specialist care and reassess diagnosis". Do not route patients with active severe pulmonary disease directly to an ICI rechallenge decision. Important consideration There is no universally effective or standardized sequence of third-line immunosuppressive treatment. Further decisions must reflect clinical severity, competing diagnoses, previous treatments, and patient-specific risks.

Resume immune checkpoint inhibitor treatment only after an individualized multidisciplinary risk–benefit assessment confirms that rechallenge is appropriate. Before restarting ICI Document: ICI agent and proposed treatment regimen. Previous pneumonitis grade and clinical severity. Evidence of clinical and radiographic recovery. Current respiratory symptoms and baseline oxygen requirements. Current corticosteroid dose and any ongoing immunosuppression. Anticipated oncologic benefit and available alternatives. Patient-informed decision and agreed monitoring plan. Early monitoring after rechallenge Arrange early clinical reassessment following ICI resumption. Assess: New or recurrent cough. Dyspnea at rest or during exertion. Chest discomfort or fever. Oxygen saturation when clinically appropriate. Functional status and exercise tolerance. Any new or increasing oxygen requirement. Review respiratory symptoms before subsequent ICI administrations. Consider chest CT when symptoms recur or when clinically indicated by previous pneumonitis severity and pulmonary risk. Patient education Provide clear instructions for promptly reporting new respiratory symptoms. Explain that recurrent pneumonitis may require ICI interruption, corticosteroids, hospitalization, or permanent treatment discontinuation. Ensure the patient knows how to contact the oncology team and when urgent medical assessment is required. If pneumonitis recurs Hold ICI and restart diagnostic assessment and severity grading. Reassess infection and other potential pulmonary causes. Determine whether further immunotherapy remains appropriate based on recurrence severity and the expected oncologic benefit. Important treatment principle ICI dose reduction is not an established strategy for preventing recurrence of immune-mediated pneumonitis. Do not reduce the ICI dose empirically as an alternative to appropriate interruption or discontinuation. Ongoing follow-up Maintain communication between oncology and pulmonology. Continue appropriate monitoring for recurrent pneumonitis and persistent pulmonary impairment.

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.

Confirm sustained clinical and radiographic recovery following treatment of ICI-related pneumonitis. Recovery assessment is necessary regardless of whether ICI will be resumed or permanently discontinued. Clinical recovery Assess: Resolution or substantial improvement of cough and dyspnea. Improvement in respiratory effort. Return of oxygen requirements toward baseline. Recovery of functional capacity and activity tolerance. Absence of new respiratory deterioration. Symptoms should ideally return to baseline or Grade 1 before considering possible ICI resumption. Radiographic recovery Review follow-up chest CT for improvement or resolution of inflammatory pulmonary infiltrates. Persistent or progressive abnormalities require further pulmonary assessment, particularly when accompanied by symptoms or oxygen requirements. Additional recovery assessment Document: Current corticosteroid dose and taper schedule. Any ongoing second-line immunosuppressive treatment. Infection status. Residual dyspnea or supplemental oxygen needs. Functional limitations or possible chronic pulmonary impairment. Consider pulmonary function tests, including spirometry and DLCO, when clinically useful. ICI rechallenge eligibility Clinical recovery does not automatically establish eligibility for rechallenge. Patients with previous Grade 3–4 ICI pneumonitis should follow the permanent-discontinuation pathway according to ASCO guidance. Selected patients recovering from Grade 1–2 pneumonitis may proceed to an individualized rechallenge assessment when clinically and oncologically appropriate. Long-term monitoring Arrange appropriate pulmonary follow-up for recurrent symptoms, residual radiographic changes, corticosteroid complications, and late respiratory toxicity. Maintain communication between oncology and pulmonology.

Continue active multidisciplinary management for severe ICI-related pneumonitis with inadequate response to second-line treatment, or clinically significant recurrence requiring specialized reassessment. This node represents continued active care, not observation alone or automatic cessation of pulmonary treatment. Ongoing respiratory management Maintain hospital-based monitoring and respiratory support according to severity. Reassess oxygenation, ventilatory requirements, respiratory effort, and hemodynamic stability. Review chest imaging and pulmonary complications. Monitor corticosteroid toxicity and adverse effects of additional immunosuppressive medications. Involve critical care when respiratory failure progresses. Diagnostic reassessment Reconsider the initial diagnosis and the possibility of concurrent infection. Evaluate: Bacterial, viral, and fungal pneumonia. Pneumocystis jirovecii and other opportunistic infections. Pulmonary embolism. Radiation pneumonitis or another drug-related pulmonary toxicity. Tumor progression or lymphangitic carcinomatosis. Pulmonary edema. Diffuse alveolar hemorrhage. Other interstitial lung diseases. Repeat chest CT and consider bronchoscopy with BAL or other targeted investigations when clinically useful and safe. Further specialist treatment An experienced multidisciplinary team should determine whether additional immunomodulatory treatment, modification of the current regimen, antimicrobial treatment, or enhanced respiratory support is appropriate. There is no validated automatic third-line rescue sequence. Avoid indiscriminate combination immunosuppression when active infection or another competing diagnosis has not been adequately assessed. Recurrence during corticosteroid taper Confirm whether worsening symptoms represent recurrent immune-mediated pneumonitis, infection, or another pulmonary disorder. Reassess clinical severity and return to the appropriate severity-directed treatment pathway when necessary. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. ICI disposition Previous Grade 3–4 ICI pneumonitis remains an indication for permanent ICI discontinuation under ASCO pneumonitis-specific guidance, regardless of subsequent pulmonary improvement. Continue pulmonary treatment, appropriate rehabilitation, supportive care, and individualized goals-of-care discussions when indicated.

Resume immune checkpoint inhibitor treatment only after an individualized multidisciplinary risk–benefit assessment confirms that rechallenge is appropriate. Before restarting ICI Document: ICI agent and proposed treatment regimen. Previous pneumonitis grade and clinical severity. Evidence of clinical and radiographic recovery. Current respiratory symptoms and baseline oxygen requirements. Current corticosteroid dose and any ongoing immunosuppression. Anticipated oncologic benefit and available alternatives. Patient-informed decision and agreed monitoring plan. Early monitoring after rechallenge Arrange early clinical reassessment following ICI resumption. Assess: New or recurrent cough. Dyspnea at rest or during exertion. Chest discomfort or fever. Oxygen saturation when clinically appropriate. Functional status and exercise tolerance. Any new or increasing oxygen requirement. Review respiratory symptoms before subsequent ICI administrations. Consider chest CT when symptoms recur or when clinically indicated by previous pneumonitis severity and pulmonary risk. Patient education Provide clear instructions for promptly reporting new respiratory symptoms. Explain that recurrent pneumonitis may require ICI interruption, corticosteroids, hospitalization, or permanent treatment discontinuation. Ensure the patient knows how to contact the oncology team and when urgent medical assessment is required. If pneumonitis recurs Hold ICI and restart diagnostic assessment and severity grading. Reassess infection and other potential pulmonary causes. Determine whether further immunotherapy remains appropriate based on recurrence severity and the expected oncologic benefit. Important treatment principle ICI dose reduction is not an established strategy for preventing recurrence of immune-mediated pneumonitis. Do not reduce the ICI dose empirically as an alternative to appropriate interruption or discontinuation. Ongoing follow-up Maintain communication between oncology and pulmonology. Continue appropriate monitoring for recurrent pneumonitis and persistent pulmonary impairment.

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.

Confirm sustained clinical and radiographic recovery following treatment of ICI-related pneumonitis. Recovery assessment is necessary regardless of whether ICI will be resumed or permanently discontinued. Clinical recovery Assess: Resolution or substantial improvement of cough and dyspnea. Improvement in respiratory effort. Return of oxygen requirements toward baseline. Recovery of functional capacity and activity tolerance. Absence of new respiratory deterioration. Symptoms should ideally return to baseline or Grade 1 before considering possible ICI resumption. Radiographic recovery Review follow-up chest CT for improvement or resolution of inflammatory pulmonary infiltrates. Persistent or progressive abnormalities require further pulmonary assessment, particularly when accompanied by symptoms or oxygen requirements. Additional recovery assessment Document: Current corticosteroid dose and taper schedule. Any ongoing second-line immunosuppressive treatment. Infection status. Residual dyspnea or supplemental oxygen needs. Functional limitations or possible chronic pulmonary impairment. Consider pulmonary function tests, including spirometry and DLCO, when clinically useful. ICI rechallenge eligibility Clinical recovery does not automatically establish eligibility for rechallenge. Patients with previous Grade 3–4 ICI pneumonitis should follow the permanent-discontinuation pathway according to ASCO guidance. Selected patients recovering from Grade 1–2 pneumonitis may proceed to an individualized rechallenge assessment when clinically and oncologically appropriate. Long-term monitoring Arrange appropriate pulmonary follow-up for recurrent symptoms, residual radiographic changes, corticosteroid complications, and late respiratory toxicity. Maintain communication between oncology and pulmonology.

Continue active multidisciplinary management for severe ICI-related pneumonitis with inadequate response to second-line treatment, or clinically significant recurrence requiring specialized reassessment. This node represents continued active care, not observation alone or automatic cessation of pulmonary treatment. Ongoing respiratory management Maintain hospital-based monitoring and respiratory support according to severity. Reassess oxygenation, ventilatory requirements, respiratory effort, and hemodynamic stability. Review chest imaging and pulmonary complications. Monitor corticosteroid toxicity and adverse effects of additional immunosuppressive medications. Involve critical care when respiratory failure progresses. Diagnostic reassessment Reconsider the initial diagnosis and the possibility of concurrent infection. Evaluate: Bacterial, viral, and fungal pneumonia. Pneumocystis jirovecii and other opportunistic infections. Pulmonary embolism. Radiation pneumonitis or another drug-related pulmonary toxicity. Tumor progression or lymphangitic carcinomatosis. Pulmonary edema. Diffuse alveolar hemorrhage. Other interstitial lung diseases. Repeat chest CT and consider bronchoscopy with BAL or other targeted investigations when clinically useful and safe. Further specialist treatment An experienced multidisciplinary team should determine whether additional immunomodulatory treatment, modification of the current regimen, antimicrobial treatment, or enhanced respiratory support is appropriate. There is no validated automatic third-line rescue sequence. Avoid indiscriminate combination immunosuppression when active infection or another competing diagnosis has not been adequately assessed. Recurrence during corticosteroid taper Confirm whether worsening symptoms represent recurrent immune-mediated pneumonitis, infection, or another pulmonary disorder. Reassess clinical severity and return to the appropriate severity-directed treatment pathway when necessary. Not every recurrence during taper represents resistance to adequate-dose intravenous corticosteroids. ICI disposition Previous Grade 3–4 ICI pneumonitis remains an indication for permanent ICI discontinuation under ASCO pneumonitis-specific guidance, regardless of subsequent pulmonary improvement. Continue pulmonary treatment, appropriate rehabilitation, supportive care, and individualized goals-of-care discussions when indicated.

Resume immune checkpoint inhibitor treatment only after an individualized multidisciplinary risk–benefit assessment confirms that rechallenge is appropriate. Before restarting ICI Document: ICI agent and proposed treatment regimen. Previous pneumonitis grade and clinical severity. Evidence of clinical and radiographic recovery. Current respiratory symptoms and baseline oxygen requirements. Current corticosteroid dose and any ongoing immunosuppression. Anticipated oncologic benefit and available alternatives. Patient-informed decision and agreed monitoring plan. Early monitoring after rechallenge Arrange early clinical reassessment following ICI resumption. Assess: New or recurrent cough. Dyspnea at rest or during exertion. Chest discomfort or fever. Oxygen saturation when clinically appropriate. Functional status and exercise tolerance. Any new or increasing oxygen requirement. Review respiratory symptoms before subsequent ICI administrations. Consider chest CT when symptoms recur or when clinically indicated by previous pneumonitis severity and pulmonary risk. Patient education Provide clear instructions for promptly reporting new respiratory symptoms. Explain that recurrent pneumonitis may require ICI interruption, corticosteroids, hospitalization, or permanent treatment discontinuation. Ensure the patient knows how to contact the oncology team and when urgent medical assessment is required. If pneumonitis recurs Hold ICI and restart diagnostic assessment and severity grading. Reassess infection and other potential pulmonary causes. Determine whether further immunotherapy remains appropriate based on recurrence severity and the expected oncologic benefit. Important treatment principle ICI dose reduction is not an established strategy for preventing recurrence of immune-mediated pneumonitis. Do not reduce the ICI dose empirically as an alternative to appropriate interruption or discontinuation. Ongoing follow-up Maintain communication between oncology and pulmonology. Continue appropriate monitoring for recurrent pneumonitis and persistent pulmonary impairment.

Permanently discontinue ICI after Grade 3–4 immune-mediated pneumonitis according to ASCO pneumonitis-specific recommendations. Avoid rechallenge when pulmonary toxicity remains active or when the anticipated risks outweigh the expected oncologic benefits. Reasons to avoid rechallenge These may include: Previous Grade 3–4 immune-mediated pneumonitis. Severe or recurrent pulmonary toxicity. Persistent oxygen requirements. Clinically significant residual pulmonary dysfunction. Ongoing corticosteroid dependence or additional immunosuppressive treatment. Previous steroid-refractory pneumonitis. Unresolved radiographic abnormalities with clinically significant respiratory impairment. An unfavorable individualized oncologic risk–benefit assessment. Document the decision Specify whether permanent ICI discontinuation is required by pneumonitis-specific guidelines or product labeling, or whether the decision reflects an individualized multidisciplinary assessment. Record the initial pneumonitis grade, treatments administered, complications, recovery status, and rationale for avoiding rechallenge. Continue pulmonary management Permanent discontinuation of ICI does not mean discontinuation of pneumonitis treatment. Continue: Appropriate corticosteroid treatment and gradual tapering. Management of active or recurrent pulmonary inflammation. Monitoring for opportunistic infections. Evaluation of corticosteroid-related complications. Respiratory rehabilitation and oxygen support when indicated. Clinical and radiographic follow-up. For unresolved steroid-refractory disease, continue specialist-directed pulmonary management. Oncologic treatment planning Discuss alternative anticancer treatments according to the patient's disease status, previous therapies, expected benefit, and treatment goals. Consider multidisciplinary input when alternative systemic strategies are limited. Document the planned oncologic treatment and follow-up. Communication and continuity of care Communicate the history of immune-mediated pneumonitis and the decision regarding ICI discontinuation to all treating clinicians. Ensure the patient understands that ICI discontinuation does not mean withdrawal of ongoing pulmonary or oncologic care. Key safety message Stopping ICI does not stop care.