LDH Levels Could Predict irAEs Associated With Checkpoint Inhibition and Radiotherapy in Lung Cancer

Evidence-Based Oncology, July 2017, Volume 23, Issue SP8

A study presented by researchers from Massachusetts General Hospital (MGH), which queried the effect of thoracic radiotherapy and immune checkpoint inhibition on the risk of pneumonitis or immune-related adverse events (irAEs), found that radiotherapy did not increase patient risk for pneumonitis and that elevated expression of lactate dehydrogenase (LDH) could be a predictor of grade 2 or higher irAEs.

A STUDY PRESENTED BY

researchers from Massachusetts General Hospital (MGH), which queried the effect of thoracic radiotherapy and immune checkpoint inhibition on the risk of pneumonitis or immune-related adverse events (irAEs), found that radiotherapy did not increase patient risk for pneumonitis. Additionally, the study, presented as a poster, found that elevated expression of lactate dehydrogenase (LDH) could be a predictor of grade 2 or higher irAEs.1

The newer immune checkpoint inhibitors have been documented to cause unique irAEs, which can result in patients dropping out of a treatment schedule.2 Although an increased risk of pneumonitis is a known effect of thoracic radiotherapy, the authors of the current study were interested in evaluating the effect of the combination treatment on the risk of pneumonitis or other irAEs. The study also examined the importance of serum LDH in predicting irAEs associated with the immune checkpoint treatment.

Clinicopathological and response data on 164 patients who received treatment for metastatic lung cancer (95% non—small cell lung cancer and 5% small cell lung cancer) at MGH between 2013 and 2016, were retrospectively analyzed. Patient data included at least a 1-month follow-up, except in cases of rapid death from an irAE (n = 4); cohorts were formed based on receipt of thoracic radiotherapy.

Seventy-three patients received thoracic radiotherapy and 91 did not. Baseline characteristics such as age, gender, smoking status, supplemental oxygen requirement, median number of chemotherapy lines prior to immune checkpoint treatment (1 vs 1, respectively), median cycles of immune checkpoint treatment (5 vs 3), and median follow-up after immune checkpoint treatment initiation (8 months vs 7 months) were similar in the 2 cohorts.

The study found that the rates of grade 2 and higher irAEs (18.1 vs 14.4%; P = .67), all-grade pneumonitis (8.2 vs 5.5%; P = .54), and grade 2 and higher pneumonitis (4.1 vs 3.3%; P = 1) were not significantly different between the radiotherapy versus no radiotherapy cohorts, respectively. There was no difference between the mean thoracic radiotherapy dose either, between those patients who developed pneumonitis and those who did not (55.8 vs 55.9 Gy). About 85% of patients received the radiotherapy for a median 8.6 months before checkpoint inhibitor treatment. Of the 7 patients (10%) who had concurrent treatment, none developed symptomatic pneumonitis. Notably, patients with grade 2 and higher irAEs (n = 26) had significantly higher mean serum LDH before initiation of the checkpoint inhibitor treatment than patients who did not (283 IU/L vs 214 IU/L; ref 98 to 192 IU/L; P = .03).

The authors concluded that thoracic radiotherapy in patients with lung cancer who received immune checkpoint treatment was not associated with increased risk of pneumonitis and that LDH may be a negative predictive biomarker for grade 2 and higher irAEs.REFERENCES

1. Hwang WL, Niemierko A, Willers H, Keane FK, Gainor JF. Immune-related adverse events (IRAEs) in metastatic lung cancer patients receiving PD-1/PD-L1 inhibitors and thoracic radiotherapy. J Clin Oncol. 2017;35(suppl; abst 9079).

2. Dangi-Garimella S. Sustained response to immune checkpoint inhibitors could influence standard of care. The American Journal of Managed Care® website. ajmc.com/newsroom/sustained-response-to-immune-checkpoint-inhibitors-could-influence-standard-of-care. Published February 14, 2017. Accessed June 26, 2017.