ABSTRACT
The discovery of tyrosine kinase oncogenic driver mutations, including anaplastic lymphoma kinase (ALK), has changed the face of non-small cell lung cancer (NSCLC) treatment. Whilst the development of tyrosine kinase inhibitors has improved survival, with their increasing use, it is important to be aware of the risks of rare yet serious adverse events, such as drug-induced pulmonary toxicity. Whilst little is known in regard to drug-induced pneumonitis in the setting of ALK inhibitors, such reactions carry a high morbidity and mortality rate, impacting greatly upon options for further treatment and management. We describe the case of a 73-year-old female with metastatic ALK-positive NSCLC who developed subacute dyspnoea 3 weeks after commencing lorlatinib. She was diagnosed with drug-induced pneumonitis, from which she recovered clinically following the cessation of her targeted therapy. Pneumonitis related to lorlatinib is a rare pulmonary toxicity, and early recognition and intervention is critical to reduce the associated risks of respiratory failure and death.
ABSTRACT
PURPOSE OF REVIEW: Immune checkpoint inhibitors have revolutionised the treatment of multiple malignancies and have a growing list of indications. As our familiarity with these agents grows, so does our understanding of their unique spectrum of toxicities. Here, we will review the literature regarding the toxicities of checkpoint inhibitors and address challenges encountered in day-to-day clinical practice. RECENT FINDINGS: Inhibitors of the PD-1/PD-L1 axis are considerably less toxic than the anti-CTLA-4 antibody ipilimumab. The combination of ipilimumab and anti-PD-1 agents is being trialled in multiple malignancies and is associated with increased toxicity. There is accumulating evidence suggesting a potential correlation between a subset of toxicities and clinical benefit in several tumour types, although conflicting data exists. Retrospective series have shown that anti-PD-1 can be safely administered to patients with prior high-grade toxicity from ipilimumab or combination immunotherapy. The management of checkpoint inhibitor toxicity is complex and requires collaboration with our subspecialty colleagues. Identifying predictive biomarkers of both efficacy and toxicity would likely help guide treatment decisions, and should be a research priority in the years ahead.
