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PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course.

ABSTRACT: Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.Among 170 patients treated in 10 different trials of nivolumab, 20 patients (10 melanoma, 6 lymphoma, and 4 lung cancer) developed pneumonitis. Five patients received nivolumab monotherapy, and 15 received combination therapy. The median time from therapy initiation to pneumonitis was 2.6 months. Radiographic pattern was cryptogenic organizing pneumonia (COP) in 13, nonspecific interstitial pneumonia (NSIP) in 3, hypersensitivity pneumonitis (HP) in 2, and acute interstitial pneumonia (AIP)/acute respiratory distress syndrome (ARDS) in 2 patients. The AIP/ARDS pattern had the highest grade, followed by COP, whereas NSIP and HP had lower grade (median grade: 3, 2, 1, 1, respectively; P = 0.006). The COP pattern was most common in all tumors and treatment regimens. Most patients (17/20; 85%) received corticosteroids, and 3 (15%) also required infliximab. Seven patients restarted nivolumab therapy; 2 of them developed recurrent pneumonitis and were successfully retreated with corticosteroids. One of the patients experienced a pneumonitis flare after completion of corticosteroid taper without nivolumab retreatment.PD-1 inhibitor-related pneumonitis showed a spectrum of radiographic patterns, reflecting pneumonitis grades. COP was the most common pattern across tumor types and therapeutic regimens. Most patients were successfully treated with corticosteroids. Recurrent pneumonitis and pneumonitis flare were noted in a few patients. Clin Cancer Res; 22(24); 6051-60. ©2016 AACRSee related commentary by Castanon, p. 5956.

SUBMITTER: Nishino M

PROVIDER: S-EPMC5161686 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course.

Nishino Mizuki M Ramaiya Nikhil H NH Awad Mark M MM Sholl Lynette M LM Maattala Jennifer A JA Taibi Myriam M Hatabu Hiroto H Ott Patrick A PA Armand Philippe F PF Hodi F Stephen FS

Clinical cancer research : an official journal of the American Association for Cancer Research 20160817 24

<h4>Purpose</h4>Investigate the clinical characteristics, radiographic patterns, and treatment course of PD-1 inhibitor-related pneumonitis in advanced cancer patients.<h4>Experimental design</h4>Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Chest CT scans were reviewed to assess extent, distribution, and radiographic patterns of pneumonitis.<h4>Results</h4>Among 170 patients treated in 10 different ...[more]

PMID: 27535979

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Project description:BackgroundCheckpoint inhibitor-related pneumonitis (CIP) induced by immune checkpoint inhibitors (ICIs) is one of the most fatal immune-related adverse events (irAE). However, only limited data are available on rechallenge with ICIs after CIP. We evaluated the efficacy and safety of rechallenge after CIP in patients with advanced lung cancer to identify the potential populations that would benefit.MethodsWe conducted a multicenter retrospective study of advanced lung cancer patients who received further ICI treatment (rechallenge) or did not undergo re-administration after grade ≥1 CIP between May 2017 and May 2021. Progression-free survival (PFS) and overall survival (OS) were estimated from first or second ICI initiation to disease progression (PFS1 and PFS2, respectively), death, or last follow-up (OS1 and OS2, respectively). The recurrence of CIP and new irAEs in these patients after ICI rechallenge were calculated.ResultsAmong 107 patients afflicted with CIP, 45 (42.1%) received ICI rechallenge. Multivariate analysis showed that severe grade (grades ≥3) and ground-glass opacity of pneumonitis lesions were negatively associated with rechallenge. Following rechallenge, 9 (20.0%) patients developed recurrent pneumonitis, and 11 (24.4%) developed a new irAE. Severe grade of CIP and poor performance status at initial CIP as well as levels of interleukin (IL)-6 and C-reactive protein (CRP), and absolute white blood cell and neutrophil counts at the time of ICI rechallenge were associated with a higher recurrence rate. The median (95% confidence interval) PFS1 and PFS2 were 17.9 (9.9-24.2) and 15.5 (5.5-25.6) months, respectively. The median (95% confidence interval) OS1 and OS2 were 23.5 (16.5-30.5) and 18.4 (10.1-26.7) months, respectively. Lower OS2 was observed in patients with severe grade of CIP and poor performance status at the initial CIP, recurrence of CIP, and in patients with high levels of CRP and IL-6 at rechallenge. Only IL-6 was found to affect OS2 on multivariate analysis.ConclusionsICI rechallenge following CIP may be a promising treatment for patients with advanced lung cancer, particularly in those with low-grade of CIP and good performance status at initial CIP, and low levels of IL-6 and CRP at the time of initial challenge. Prospective studies are needed for further verification.

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Dataset Information

PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course.

Publications

PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course.

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