Clinical Features, Survival, and Burden of Toxicities in Survivors More Than One Year After Lung Cancer Immunotherapy

Abstract

Introduction: Anti-PD-(L)1 immune checkpoint inhibitors (ICI) improve survival in patients with advanced non-small cell lung cancer (aNSCLC). The clinical features, survival, and burden of toxicities of patients with aNSCLC alive >1 year from ICI initiation are poorly understood.

Materials and methods: We defined ICI survivors as patients alive >1 year after ICI start and retrospectively reviewed demographics, treatment, and immune-related adverse events (irAEs). Long-term irAEs were defined as ongoing irAEs lasting >1 year; burden of toxicity measures were based on percentage of days a patient experienced toxicity. Using linear and logistic regression, we evaluated association between demographics and disease characteristics with burden of toxicity.

Results: We identified 114 ICI survivors from 317 patients with aNSCLC. Half (52%) experienced an irAE of any grade, and 23.7% developed long-term irAEs. More ICI survivors with irAES in the first year had never smoked (P = .018) or received ICIs as frontline therapy (P = .015). The burden of toxicity in the first year significantly correlated with the burden of toxicity afterward (ρ = 0.72; P < .001). No patients with progressive disease had a high burden of toxicity, and they experienced 30.6% fewer days with toxicity than those with stable disease. Increased duration of therapy was associated with higher odds of experiencing toxicity. Half of ICI survivors with irAEs were still receiving treatment for unresolved irAEs at time of death or last follow-up.

Conclusion: Significant proportions of ICI survivors have unresolved long-term toxicities. These data support a growing need to understand long-term toxicity to optimize management of those treated with ICIs.

Keywords: immune checkpoint inhibitors; immune-related adverse events; non-small cell lung cancer; survivorship; toxicities.

Figure 1.

Patients with non-small cell lung cancer treated with immune checkpoint inhibitors at Johns Hopkins University between November 2009 and February /2019. Of 317 aNSCLC patients treated with ICIs, 114 were classified as ICI survivors.

Figure 2.

Time to development of immune-related adverse events (irAEs) in ICI survivors. Time to irAE was compared for patients experience a single irAE (top) and more than one, or multisystem, irAE (bottom). Each dot represents the time to irAE from ICI treatment initiation. Median time to irAE events are depicted as vertical lines. Median time to first irAE event was compared by Wilcoxon rank-sum test between patients in the single and multi-system irAE groups (P = .03). For multisystem irAEs, the median time to fourth (blue) or fifth (pink) irAEs were the same and are overlapping in the figure.

Figure 3.

Swimmer plots of ICI survivors stratified by those with unresolved versus resolved irAEs. Each row represents one patient who had unresolved (left) or resolved (right) irAEs during follow-up. The darker gray bars reflect time on immunotherapy and lighter gray bars reflect follow-up or death; arrows at the end of the bars reflect living ICI survivors at the time of data cutoff. Overlying these bars, the duration, grade, and treatment of irAEs are depicted. Grade of the irAE is depicted by color. A dashed line indicates untreated irAEs, and a solid line indicates irAEs that were treated.