Abemaciclib Should NOT Be Resumed During Active Pneumonia
Abemaciclib must be discontinued immediately in patients with active pneumonitis/pneumonia and should only be resumed after complete resolution to baseline or Grade 1, at a reduced dose. 1
FDA-Mandated Management of Interstitial Lung Disease/Pneumonitis
The FDA prescribing information for abemaciclib (Verzenio) provides explicit dose modification requirements for pneumonitis: 1
- Grade 1 or 2 pneumonitis: No dose modification required if mild
- Persistent or recurrent Grade 2 that does not resolve within 7 days: Suspend dose until toxicity resolves to baseline or ≤Grade 1, then resume at next lower dose
- Grade 3 or 4 pneumonitis: Permanently discontinue abemaciclib 1
Active pneumonia represents at minimum Grade 2-3 toxicity, requiring immediate drug suspension. 1
Clinical Evidence on Abemaciclib-Induced Pneumonitis
Incidence and Severity
Interstitial lung disease/pneumonitis occurs in approximately 3-3.4% of patients treated with abemaciclib, with severity ranging from mild to fatal. 1, 2
Fatal Cases Documented
A fatal case of severe pneumonitis with superimposed fungal respiratory infection occurred in a 65-year-old woman with metastatic breast cancer receiving abemaciclib, complicated by hypogammaglobulinemia and cellular immunodeficiency. 3 This underscores that abemaciclib carries a black box warning for rare but potentially fatal severe pneumonitis. 3
Histological Findings
The first case report with histological confirmation demonstrated that abemaciclib-induced pneumonitis presents with: 4
- Organizing pneumonia pattern on high-resolution CT
- Lymphocytosis on bronchoalveolar lavage
- Alveolitis with epithelial cell injury on transbronchial biopsy
- Elevated KL-6 and surfactant protein-D levels 4
This case required both abemaciclib discontinuation AND prednisolone treatment for resolution. 4
Management Algorithm for Active Pneumonia
Immediate Actions Required
- Suspend abemaciclib immediately upon diagnosis of pneumonia 1
- Treat pneumonitis with corticosteroids and/or antibiotics as clinically indicated 2
- Monitor with chest imaging, KL-6, and SP-D levels 4
Criteria for Potential Resumption
Abemaciclib may only be considered for resumption when ALL of the following are met: 1
- Pneumonitis has completely resolved to baseline or Grade 1
- Patient is clinically stable without respiratory symptoms
- Radiographic abnormalities have resolved
- At least 7 days have passed since resolution 1
When resuming, ALWAYS reduce to the next lower dose level (e.g., from 150 mg twice daily to 100 mg twice daily, or from 100 mg to 50 mg twice daily). 1
If Grade 3-4 Pneumonitis
Permanently discontinue abemaciclib—do NOT attempt resumption. 1
Critical Clinical Pitfalls
Do Not Underestimate Severity
The MONARCH 2 and 3 trials demonstrated that while pneumonitis is infrequent (3.4%), it requires aggressive management with corticosteroids and/or antibiotics, and the severity can be life-threatening. 2
Immunosuppression Risk
Abemaciclib can trigger cellular immunodeficiency and hypogammaglobulinemia, increasing susceptibility to opportunistic infections including fungal pneumonia. 3 Active pneumonia in the setting of abemaciclib may represent superimposed infection on drug-induced lung injury.
Regular Monitoring Essential
Given that abemaciclib-induced pneumonitis can present with a "partly appearing and disappearing organizing pneumonia pattern" even without clinical symptoms, regular monitoring with chest imaging and biomarkers (KL-6, SP-D) should be considered during treatment. 4
Quality of Life and Treatment Continuation
The efficacy of abemaciclib is not compromised by dose reductions—progression-free survival benefit is maintained even with dose adjustments for toxicity management. 2 Therefore, prioritizing patient safety by suspending treatment during active pneumonia and resuming at a lower dose does not sacrifice oncologic outcomes.