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Background: Pneumonitis (Pn) is a potentially life-threatening adverse event of some anticancer drugs. We compared treatment associated pneumonitis (TAP) related to immune checkpoint inhibitors (ICI) or chemotherapies (chemo) in advanced non-small cell lung cancer (aNSCLC) patients (pts) with and without (+/-) past medical history (PMH) of Pn, using data from clinical trials (CT) and real world data (RWD). Methods: Pts with PMH Pn in 8 aNSCLC CT comparing ICI to chemo, were identified using terms pneumonitis, acute interstitial pneumonitis, pneumonitis chemical, and interstitial lung disease. aNSCLC pts treated with ICI (+/- chemo) or chemo [without concurrent radiation therapy (RT)] were identified using RWD from a community health system; Pn was defined using terms in ICD-9 and ICD-10 including pneumonitis or associated concepts in the Unified Medical Language System. RWD pts were selected using core eligibility criteria from CT. In CT and RWD, Pn incidence proportion was calculated for 4 subgroups: pts (+/-) PMH of Pn and treated with ICI vs chemo. Pn diagnosis type, including RT Pn, was assessed. Results: In CT and RWD, a higher incidence of TAP was observed among aNSCLC pts with PMH of Pn compared to those without PMH of Pn, among ICI and chemo groups (Table 1). In CT pts without PMH of Pn, ICI associated Pn was more common than chemo associated Pn. Similar rates of TAP were observed in the CT and RWD. In RWD, Pn at any time was strongly associated with RT in ICI and chemo groups, with 73% of all diagnoses of Pn due to RT. Conclusion: PMH of Pn in pts with aNSCLC is associated with a greater risk of TAP for ICI and chemo groups, in CT and RWD. RWD data suggests RT to be a frequent cause of Pn. Only in CT data, and only for pts without PMH Pn, was there a demonstrated difference in TAP incidence between ICI and chemo groups. Additional research (e.g. inclusion of pts treated with tyrosine kinase inhibitors) is warranted to optimize treatment for cancer pts with PMH of Pn. Pneumonitis incidence and 95% CI among aNSCLC patients treated with immunotherapy and chemotherapyCT patients treated with immune checkpoint inhibitors +/-chemo (N=3723)CT patients treated with chemotherapies (N=2768)RWD patients treated with immune checkpoint inhibitors +/-chemo (N=615)RWD patients treated with chemotherapies (N= 647)patients with past medical history of pneumonitis (N=48 for CT; N=33 for RWD)5/30 (16.7%;7.3-33.6%)2/18 (11.1%;3.1-32.8%)3/21 (14.3%;5.0-34.6%)1/12 (8.3%; 0.4-35.4%)patients without past medical history of pneumonitis (N=6443 for CT; N=1229 for RWD)164/3693(4.4%; 3.8-5.2%)27/2750(1.0%; 0.7-1.4%)17/594 (2.9%; 1.8-4.5%)14/635 (2.2%; 1.3-3.7%)All patients (N=6491 for CTs; N=1262 for RWD)169/3723(4.5%; 3.9-5.3%)29/2768(1.0%; 0.7-1.5%)20/615 (3.3; 2.1-5.0%)15/647(2.3; 1.4-3.8%) Citation Format: Qi Liu, Chenan Zhang, Yutao Gong, Hao Zhu, Elaine Chang, Cheryl Cho-Phan, Jonathan Hirsch, Michael A. Thompson, Gideon Blumenthal, Shiew Mei Huang, Thomas D. Brown. Pneumonitis incidence in patients with non-small cell lung cancer treated with immunotherapy or chemotherapy in clinical trials and real-world data [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT086.

The objective of this study was to compare the efficacy and safety of nivolumab in the HIV-infected and HIV-uninfected veteran populations. WHAT IS NEW: Most clinical trials highlighting checkpoint inhibitors excluded people living with HIV (PLWH). This is the first study to report equivalent nivolumab tumor response rates in PLWH, but higher rates of pneumonitis.METHODS: We searched the Corporate Data Warehouse (CDW) to identify all HIV-positive patients who used the Veterans Health Administration (VA) between 2000 and 2016. For this cohort of 46,916 PLWH, we obtained a 4:1 age-matched HIV-negative control cohort. We used pharmacy database to identify all nivolumab recipients through July 26, 2017. We reviewed patients' electronic medical records using Compensation and Pension Records Interchange (CAPRI) to obtain age, sex, geographic location, cancer type, number of nivolumab doses received, previous cancer therapy, adverse events, and response to therapy. We calculated summary descriptive measures for both groups and compared the proportion of patients experiencing adverse event or pneumonitis in groups by HIV status, using chi-square or Fisher's exact test. RESULTS: Sixteen PLWH and 68 HIV-negative controls received nivolumab during the study period. Only 51 controls had accessible data. Median age at nivolumab initiation was 65 years in both groups (range, 47-85 [IQR, 59-68] in PLWH; range, 42-79 [IQR 59-68] in controls); all patients were male. Overall, 63% received nivolumab for non-small cell lung cancer (NSCLC): 8/16 (50%) in PLWH, 34/51 (67%) in controls. Other indications in PLWH included renal cell carcinoma (RCC) (2/16 [13%]), Hodgkin lymphoma (HL) (2/16 [13%]), hepatocellular carcinoma (HCC) (2/16 [13%]). Other indications in controls were RCC (9/51 [18%]), melanoma (5/51, [10%]), and head and neck squamous cell carcinoma (3/51 [6%]).Regardless of HIV status, the median number of prior lines of therapy was 1, median number of nivolumab doses received was 6, and median progression-free survival (PFS) in NSCLC was 2.75 months. Half of each NSCLC group received radiation; fewer PLWH had COPD (50%, vs. 82% of controls). PLWH had a trend towards more adverse events (AEs) (6/15 [40%], vs. 13/51 [26%] of controls, p=0.28). A significantly higher proportion of PLWH experienced pneumonitis (4/15 [27%], vs. 2/51 [4%] of controls, p=0.007).Other AEs among PLWH were rash, hypothyroidism, and autoimmune diabetes mellitus. Other AEs among controls were fatigue, colitis, rash, hypothyroidism, arthritis, and hepatitis (1-3 patients each). CONCLUSION: Among veteran PLWH, rates of nivolumab administration, and PFS in NSCLC, were comparable to those of HIV-uninfected counterparts. Pneumonitis was significantly more frequent in PLWH. Further studies should investigate the mechanism of pneumonitis in this population, confirm the high frequency in larger cohorts of PLWH, and identify clinical risk factors for pneumonitis. Citation Format: Elaine Chang, Aaron P. Thrift, Donna L. White, Jennifer Kramer, Anita L. Sabichi, Christine Hartman, Kathryn E. Royse, Peter A. Richardson, Elizabeth Y. Chiao. Nivolumab efficacy and safety in veterans with and without HIV infection [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 617.