Incidence and management of 3 years of immune mediated toxicities in metastatic non-small cell lung carcinoma (NSCLC) patients treated with anti PD-1/PD-L1 immunotherapy


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Grace Tze-en Ding1,Colin Barrie1,Alan Simms2,Melanie Mackean3
1Edinburgh Cancer Centre,2Department of Radiology, NHS Lothian,3Edinburgh

Abstract

Background

Immunotherapy (IO) has revolutionised the management of NSCLC, however, toxicities can be life threatening and prompt recognition and management are essential. We aim to study the incidence and management of immune-related toxicities in our patients.

Method

Retrospective case review of metastatic NSCLC patients treated with IO (pembrolizumab (33%) or nivolumab (67%)) identified by Chemocare reports in NHS Lothian between October 2015 to September 2018.

Results

81 NSCLC patients had IO therapy; median age 68 years. Performance status 0 (17%), 1 (75%) and 2 (8%) respectively. 28 patients (35%) experienced at least 1 immune-related toxicity and 6% ≥2 toxicities. 14% had G3 or above toxicity. 10% required treatment cessation due to toxicities.

Pneumonitis was suspected in 9 patients (11%), but only 4 were suspicious on CT imaging. All were treated empirically with steroids, however on further radiology and specialist review, symptoms were attributed to disease progression rather than pneumonitis. 9 patients (11%) had endocrinopathies, all G1 and no hospital admissions. All were treated as per guidelines and 77% required ongoing thyroid replacement. 33% needed treatment delay, but all were successfully rechallenged. 10 patients (12%) had ≥G2 skin toxicity. All G2 toxicities responded to oral steroids though doses varied. All G3 patients were given parenteral steroids. Only 1 patient was successfully rechallenged. 2 patients (3%) had ≥G2 colitis. All had abdominal X-ray but only 50% had sigmoidoscopy. 2 patients (3%) had ≥G2 hepatitis. All colitis and hepatitis patients had admission and steroids initiated within 24 hours.

There were 3 individual cases of immune-related myasthenia gravis, inflammatory arthritis and complete heart block.

Conclusion

Our local data reflects similar toxicity to trial data and patients received appropriate treatment.  Diagnosis of pneumonitis remains challenging in the context of progressive lung cancer but should prompt appropriate investigations and multidisciplinary team approach in its management.