Difference between revisions of "Immunotherapy toxicity management"
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− | !colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c"|'''Section editor''' | + | ! colspan="2" align="center" style="color:white; font-size:125%; background-color:#08519c" |'''Section editor''' |
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===Pancreas=== | ===Pancreas=== | ||
===Skin, dermatologic=== | ===Skin, dermatologic=== | ||
+ | |||
+ | '''Maculopapular rash''': the most frequent event with checkpoint inhibitors, the fourth version of the CTCAE classification proposes: | ||
+ | |||
+ | • Grade 1: macules/papules covering < 10% the body surface area (BSA) with or without symptoms (e.g. pruritus, burning, tightness); | ||
+ | |||
+ | ''MGMT: avoid skin irritants; topical steroids, anti-histamines; continue ICI;'' | ||
+ | |||
+ | • Grade 2: macules/papules covering 10%–30% BSA with or without symptoms (e.g. pruritus, burning, tightness); limiting instrumental activities of daily living (ADL); | ||
+ | |||
+ | ''MGMT: avoid skin irritants; topical steroids, anti-histamines +/- oral agents if needed; continue ICI;'' | ||
+ | |||
+ | · Non-urgent dermatology referral; consider skin biopsy | ||
+ | |||
+ | • Grade 3: macules/papules covering > 30% BSA with or without associated symptoms; limiting self-care ADL; | ||
+ | |||
+ | ''MGMT: avoid skin irritants; if mild – moderation systemic steroids 0.5-1mg/kg prednisone daily for 3 days then taper off; if more severe wean consider IV methylpred (1-2mg/kg) and slower taper over 2-4 weeks; can consider re-trial of ICI depending on severity of rash and dermatology recommendation;'' | ||
+ | |||
+ | · Dermatology referral with biopsy | ||
+ | |||
+ | '''Pruritus:''' a frequent event with checkpoint inhibitors, often can be treated supportively with topicals, anti-histamines with continuation of ICI | ||
+ | |||
+ | · Topical lotions/emollients – menthol containing hydrate skin and provide pruritus relief in mild cases (i.e. Gold Bond) | ||
+ | |||
+ | · Topical steroids (clobestasol propionate, betasmethasone dipropionate) | ||
+ | |||
+ | · Oral anti-histamines: cetirizine/loratidine daily, hydroxyzine | ||
+ | |||
+ | · If intense, limiting quality of life: oral corticosteroid – prednisone 0.5-1mg/kg/day tapered over 1-2 weeks; and dermatology referral | ||
=Guidelines= | =Guidelines= | ||
*[http://www.esmo.org/Guidelines/Supportive-and-Palliative-Care/Management-of-Toxicities-from-Immunotherapy ESMO: Management of Toxicities from Immunotherapy: ESMO Clinical Practice Guidelines (2017)] | *[http://www.esmo.org/Guidelines/Supportive-and-Palliative-Care/Management-of-Toxicities-from-Immunotherapy ESMO: Management of Toxicities from Immunotherapy: ESMO Clinical Practice Guidelines (2017)] | ||
*[https://jitc.biomedcentral.com/articles/10.1186/s40425-017-0300-z SITC: Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group] | *[https://jitc.biomedcentral.com/articles/10.1186/s40425-017-0300-z SITC: Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group] | ||
− | *Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375-91. [https://academic.oup.com/annonc/article/26/12/2375/228811 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006114/ correction of Figure 2] [https://www.ncbi.nlm.nih.gov/pubmed/26371282 PubMed] | + | *ASCO: Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline |
+ | *Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375-91. [https://academic.oup.com/annonc/article/26/12/2375/228811 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006114/ correction of Figure 2] [https://www.ncbi.nlm.nih.gov/pubmed/26371282 PubMed] | ||
=Evaluation= | =Evaluation= | ||
+ | '''''Monitoring guidelines for identification of immune-related adverse events (irAEs)''''' | ||
+ | |||
+ | · Patients should receive timely and up-to-date education about immunotherapies, their mechanism of action, and the clinical profile of possible irAEs prior to initiating therapy and throughout treatment and survivorship. | ||
+ | |||
+ | · There should be a high level of suspicion that new symptoms are treatment related. | ||
+ | |||
+ | · Recommend weekly toxicity visits for patients on combination CTLA-4/PD-1 inhibition while on therapy; every 2 or 3 week visits are reasonable for patients on single agent PD-1/L1 or CTLA-4 inhibitors | ||
+ | |||
+ | '''''Pre-treatment evaluation''''' | ||
+ | |||
+ | Detailed physical examination, including dermatologic assessment | ||
+ | |||
+ | Detailed history including personal and family history of auto-immune disease | ||
+ | |||
+ | History of bowel habits | ||
+ | |||
+ | Baseline lab evaluation: CBC, CMP, TSH | ||
+ | |||
+ | o Consider hepatitis serologies (HBsAg, HBsAb, HBcAb, hCAb), T-spot | ||
+ | |||
+ | o Consider baseline troponin, BNP | ||
+ | |||
+ | '''''General organ agnostic recommendations''''' | ||
+ | |||
+ | The following are general recommendations that should be followed irrespective of affected organs. For organ-specific management, | ||
+ | |||
+ | Per the ASCO [http://ascopubs.org/doi/full/10.1200/JCO.2017.77.6385 guidelines], clinicians should manage toxicities as follows: | ||
+ | * In general, ICI therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities. | ||
+ | * Hold ICI for most grade 2 toxicities and consider resuming when symptoms and/or laboratory values revert to grade 1 or less. | ||
+ | ** Corticosteroids (initial dose of 0.5 to 1 mg/kg/d of prednisone or equivalent) may be administered. | ||
+ | * Hold ICI for grade 3 toxicities and initiate high-dose corticosteroids prednisone 1 to 2 mg/kg/d or methylprednisolone IV 1 to 2 mg/kg/d). | ||
+ | ** Corticosteroids should be tapered over the course of at least 4 to 6 weeks. If symptoms do not improve with 48 to 72 hours of high-dose corticosteroid, should consider additional immune modulatory agents (such as infliximab for ICI-induced colitis) | ||
+ | * When symptoms and/or laboratory values revert to grade 1 or less, re-challenging with ICIs may be offered; however, caution is advised, especially in those patients with early-onset irAEs. | ||
+ | ** Dose adjustments are not recommended. | ||
+ | * In general, grade 4 toxicities warrant permanent discontinuation of ICI with rhe exception of endocrinopathies that have been controlled by hormone replacement. | ||
+ | |||
==Endocrinopathy== | ==Endocrinopathy== | ||
*ACTH | *ACTH |
Revision as of 16:33, 31 March 2018
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Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.
Section editor | |
---|---|
Meghan Mooradian, MD Boston, MA |
Grading toxicity
CTCAE
- Common Terminology Criteria for Adverse Events (CTCAE) and Common Toxicity Criteria (CTC) - Adverse event grading for clinical trials
Diarrhea, colitis
Endocrinopathy
Fatigue
Liver, hepatic
Lung, pneumonitis
Kidney, renal
Neurologic
Ocular
Pancreas
Skin, dermatologic
Maculopapular rash: the most frequent event with checkpoint inhibitors, the fourth version of the CTCAE classification proposes:
• Grade 1: macules/papules covering < 10% the body surface area (BSA) with or without symptoms (e.g. pruritus, burning, tightness);
MGMT: avoid skin irritants; topical steroids, anti-histamines; continue ICI;
• Grade 2: macules/papules covering 10%–30% BSA with or without symptoms (e.g. pruritus, burning, tightness); limiting instrumental activities of daily living (ADL);
MGMT: avoid skin irritants; topical steroids, anti-histamines +/- oral agents if needed; continue ICI;
· Non-urgent dermatology referral; consider skin biopsy
• Grade 3: macules/papules covering > 30% BSA with or without associated symptoms; limiting self-care ADL;
MGMT: avoid skin irritants; if mild – moderation systemic steroids 0.5-1mg/kg prednisone daily for 3 days then taper off; if more severe wean consider IV methylpred (1-2mg/kg) and slower taper over 2-4 weeks; can consider re-trial of ICI depending on severity of rash and dermatology recommendation;
· Dermatology referral with biopsy
Pruritus: a frequent event with checkpoint inhibitors, often can be treated supportively with topicals, anti-histamines with continuation of ICI
· Topical lotions/emollients – menthol containing hydrate skin and provide pruritus relief in mild cases (i.e. Gold Bond)
· Topical steroids (clobestasol propionate, betasmethasone dipropionate)
· Oral anti-histamines: cetirizine/loratidine daily, hydroxyzine
· If intense, limiting quality of life: oral corticosteroid – prednisone 0.5-1mg/kg/day tapered over 1-2 weeks; and dermatology referral
Guidelines
- ESMO: Management of Toxicities from Immunotherapy: ESMO Clinical Practice Guidelines (2017)
- SITC: Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group
- ASCO: Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline
- Naidoo J, Page DB, Li BT, Connell LC, Schindler K, Lacouture ME, Postow MA, Wolchok JD. Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015 Dec;26(12):2375-91. link to original article correction of Figure 2 PubMed
Evaluation
Monitoring guidelines for identification of immune-related adverse events (irAEs)
· Patients should receive timely and up-to-date education about immunotherapies, their mechanism of action, and the clinical profile of possible irAEs prior to initiating therapy and throughout treatment and survivorship.
· There should be a high level of suspicion that new symptoms are treatment related.
· Recommend weekly toxicity visits for patients on combination CTLA-4/PD-1 inhibition while on therapy; every 2 or 3 week visits are reasonable for patients on single agent PD-1/L1 or CTLA-4 inhibitors
Pre-treatment evaluation
Detailed physical examination, including dermatologic assessment
Detailed history including personal and family history of auto-immune disease
History of bowel habits
Baseline lab evaluation: CBC, CMP, TSH
o Consider hepatitis serologies (HBsAg, HBsAb, HBcAb, hCAb), T-spot
o Consider baseline troponin, BNP
General organ agnostic recommendations
The following are general recommendations that should be followed irrespective of affected organs. For organ-specific management,
Per the ASCO guidelines, clinicians should manage toxicities as follows:
- In general, ICI therapy should be continued with close monitoring for grade 1 toxicities, with the exception of some neurologic, hematologic, and cardiac toxicities.
- Hold ICI for most grade 2 toxicities and consider resuming when symptoms and/or laboratory values revert to grade 1 or less.
- Corticosteroids (initial dose of 0.5 to 1 mg/kg/d of prednisone or equivalent) may be administered.
- Hold ICI for grade 3 toxicities and initiate high-dose corticosteroids prednisone 1 to 2 mg/kg/d or methylprednisolone IV 1 to 2 mg/kg/d).
- Corticosteroids should be tapered over the course of at least 4 to 6 weeks. If symptoms do not improve with 48 to 72 hours of high-dose corticosteroid, should consider additional immune modulatory agents (such as infliximab for ICI-induced colitis)
- When symptoms and/or laboratory values revert to grade 1 or less, re-challenging with ICIs may be offered; however, caution is advised, especially in those patients with early-onset irAEs.
- Dose adjustments are not recommended.
- In general, grade 4 toxicities warrant permanent discontinuation of ICI with rhe exception of endocrinopathies that have been controlled by hormone replacement.
Endocrinopathy
- ACTH
- AM cortisol with cosyntropin stimulation test
- TSH
- FSH
- LH
- Prolactin
- Testosterone
Liver, hepatic
- Liver function tests (LFTs) or comprehensive metabolic panel (CMP)
- Hepatitis B & C serologies
- Liver/abdominal CT/MRI/ultrasound imaging
Kidney, renal
- BUN/creatinine, basic metabolic panel (BMP)
- Renal imaging (CT/MRI/ultrasound imaging)
- Urine sodium, urine urea, urine creatinine (for calculating FeNa and FeUrea)
- Kidney biopsy
Neurologic
- Electromyography (EMG)
Ocular
- Ophthalmology exam
Pancreas
- Amylase
- Lipase