Management of selected adverse events
| Adverse event . | Management recommendations . |
|---|---|
| Atrial fibrillation | • Obtain a baseline clinical risk assessment of cardiovascular risk factors before initiating therapy. |
| • New AF: Interdisciplinary risk–benefit assessment. CHA2DS2-VASc 0-1, most clinicians favor continuing BTKi therapy; ≥2, consider temporary drug hold until AF control or discontinuation. | |
| • Consider beta-blockade, often preferred as the first choice over CYP3A4 inhibitors (eg, verapamil and diltiazem) or P-glycoprotein substrates (amiodarone), which interact with BTKis. | |
| • Anticoagulation strategies include either low-dose apixaban (2.5 mg twice daily given CYP3A4 interaction) or enoxaparin (at regular doses in patients with a platelet count >50,000/μL). Where possible, avoid combination with vitamin K antagonists. | |
| Ventricular arrhythmia | • Obtain a detailed cardiac history and baseline electrocardiogram for all patients; reserve echocardiogram for patients with significant cardiac history or risk factors. |
| • Instruct patients to remain vigilant for potential early warning signs of ventricular arrhythmia and immediately investigate incident lightheadedness, palpitations, or syncope. | |
| Bleeding risk | • Commonly encountered bruising seen with BTKis does not confer an increased risk of major hemorrhage and does not necessitate cessation of therapy. |
| • When possible, send patients for necessary procedures before starting therapy. | |
| • Hold BTKis for either 3 days (minor procedure) or 7 days (major procedure) both before and after invasive procedures because of increased periprocedural bleeding risk. | |
| • For minor bleeding, holding BTKi results in the resolution of bleeding tendency in 2-3 days. For severe bleeds, transfuse platelets as appropriate to overcome clinical bleeding, regardless of platelet count. | |
| • Encourage patients with bleeding to abstain from over-the-counter supplements that may exacerbate bleeding risk, such as vitamin E or fish oil. | |
| • Consider treatment options other than BTKi when dual antiplatelet therapy is indicated. | |
| Infection | • Obtain a complete workup with an appropriate index of suspicion for opportunistic infections such as Aspergillus fumigatus and PJP. |
| • In the case of severe infection, hold BTKi until a definitive diagnosis is determined and restart after the start of clinical improvement, except in the case of fungal infections. | |
| • Provide clinically indicated vaccinations (eg, against influenza and pneumococcus) of patients before treatment initiation. | |
| • Consider PJP prophylaxis for patients deemed at high risk of infection (eg, R/R or heavily pretreated patients) or patients with a prior history of infection. | |
| Hypertension | • Optimize pharmacotherapy for control of baseline hypertension before treatment initiation. |
| • Routinely monitor and begin appropriate medical therapy for incident hypertension in conjunction with the patient’s primary care provider. | |
| Diarrhea | • Most BTKi-related diarrhea can be managed with supportive care, antimotility agents, and evening dosing of ibrutinib to mitigate symptoms. |
| • Consider temporary drug holds in the case of grade ≥3 diarrhea. | |
| Fatigue, arthralgia, and myalgia | • Avoid dosage reductions for fatigue early in the course of therapy. Search for other potential causes of fatigue when observed later in the treatment course; consider drug holiday or dosage reduction only when severe and truly drug related. |
| • Rule out other causes of arthralgia. When grade 1-2, we favor observation and supportive care. Consider dosage reduction when symptoms affect ADLs, with dose holds for grade ≥3 AEs (affecting self-care ADLs) and rechallenge at lower doses if resolution of symptoms. | |
| • Arthralgias can be adjunctively treated with pharmacotherapy, although evidence is anecdotal. Approaches include magnesium supplementation and quinine-containing tonic water. Severe arthralgias demonstrate a variable response to short-course steroids and anti-inflammatory agents. | |
| Cytopenias | • Treatment-emergent flare of autoimmune cytopenias can be managed with short-course corticosteroids or CD20 monoclonal antibody treatment, and most patients can continue BTKi therapy. |
| Dermatologic manifestations | • BTKi-related skin manifestations are often responsive to corticosteroids or dose holds. |
| • Textural changes in hair or nails can be treated with biotin supplementation and the application of nail oil. | |
| Headache | • Acalabrutinib-associated headache resolves with extended treatment and is often responsive to caffeine. |
| Adverse event . | Management recommendations . |
|---|---|
| Atrial fibrillation | • Obtain a baseline clinical risk assessment of cardiovascular risk factors before initiating therapy. |
| • New AF: Interdisciplinary risk–benefit assessment. CHA2DS2-VASc 0-1, most clinicians favor continuing BTKi therapy; ≥2, consider temporary drug hold until AF control or discontinuation. | |
| • Consider beta-blockade, often preferred as the first choice over CYP3A4 inhibitors (eg, verapamil and diltiazem) or P-glycoprotein substrates (amiodarone), which interact with BTKis. | |
| • Anticoagulation strategies include either low-dose apixaban (2.5 mg twice daily given CYP3A4 interaction) or enoxaparin (at regular doses in patients with a platelet count >50,000/μL). Where possible, avoid combination with vitamin K antagonists. | |
| Ventricular arrhythmia | • Obtain a detailed cardiac history and baseline electrocardiogram for all patients; reserve echocardiogram for patients with significant cardiac history or risk factors. |
| • Instruct patients to remain vigilant for potential early warning signs of ventricular arrhythmia and immediately investigate incident lightheadedness, palpitations, or syncope. | |
| Bleeding risk | • Commonly encountered bruising seen with BTKis does not confer an increased risk of major hemorrhage and does not necessitate cessation of therapy. |
| • When possible, send patients for necessary procedures before starting therapy. | |
| • Hold BTKis for either 3 days (minor procedure) or 7 days (major procedure) both before and after invasive procedures because of increased periprocedural bleeding risk. | |
| • For minor bleeding, holding BTKi results in the resolution of bleeding tendency in 2-3 days. For severe bleeds, transfuse platelets as appropriate to overcome clinical bleeding, regardless of platelet count. | |
| • Encourage patients with bleeding to abstain from over-the-counter supplements that may exacerbate bleeding risk, such as vitamin E or fish oil. | |
| • Consider treatment options other than BTKi when dual antiplatelet therapy is indicated. | |
| Infection | • Obtain a complete workup with an appropriate index of suspicion for opportunistic infections such as Aspergillus fumigatus and PJP. |
| • In the case of severe infection, hold BTKi until a definitive diagnosis is determined and restart after the start of clinical improvement, except in the case of fungal infections. | |
| • Provide clinically indicated vaccinations (eg, against influenza and pneumococcus) of patients before treatment initiation. | |
| • Consider PJP prophylaxis for patients deemed at high risk of infection (eg, R/R or heavily pretreated patients) or patients with a prior history of infection. | |
| Hypertension | • Optimize pharmacotherapy for control of baseline hypertension before treatment initiation. |
| • Routinely monitor and begin appropriate medical therapy for incident hypertension in conjunction with the patient’s primary care provider. | |
| Diarrhea | • Most BTKi-related diarrhea can be managed with supportive care, antimotility agents, and evening dosing of ibrutinib to mitigate symptoms. |
| • Consider temporary drug holds in the case of grade ≥3 diarrhea. | |
| Fatigue, arthralgia, and myalgia | • Avoid dosage reductions for fatigue early in the course of therapy. Search for other potential causes of fatigue when observed later in the treatment course; consider drug holiday or dosage reduction only when severe and truly drug related. |
| • Rule out other causes of arthralgia. When grade 1-2, we favor observation and supportive care. Consider dosage reduction when symptoms affect ADLs, with dose holds for grade ≥3 AEs (affecting self-care ADLs) and rechallenge at lower doses if resolution of symptoms. | |
| • Arthralgias can be adjunctively treated with pharmacotherapy, although evidence is anecdotal. Approaches include magnesium supplementation and quinine-containing tonic water. Severe arthralgias demonstrate a variable response to short-course steroids and anti-inflammatory agents. | |
| Cytopenias | • Treatment-emergent flare of autoimmune cytopenias can be managed with short-course corticosteroids or CD20 monoclonal antibody treatment, and most patients can continue BTKi therapy. |
| Dermatologic manifestations | • BTKi-related skin manifestations are often responsive to corticosteroids or dose holds. |
| • Textural changes in hair or nails can be treated with biotin supplementation and the application of nail oil. | |
| Headache | • Acalabrutinib-associated headache resolves with extended treatment and is often responsive to caffeine. |