Abstract 520: Potential role of serum proteome in predicting immune-related adverse events from immunotherapy in non-small cell lung cancer

Abstract

Early recognition of immune-related adverse events (irAEs) of immunotherapy is important. Circulating proteome reflects host response to diseases and is being explored as a marker for response to immunotherapy. We used a serum-based proteomics test, Primary Immune Response (PIR), to explore the associations between developing irAEs and immunotherapy in non-small cell lung cancer (NSCLC) patients. Data of 38 consented NSCLC patients with baseline PIR test done within one week prior to the start of immunotherapy were collected. Samples were grouped into either sensitive or intermediate/resistant (not sensitive) by PIR classification. We analyzed the durations from the immunotherapy initiation to the first episode of irAE, each individual irAE, and each irAE above grade 1 using log-rank test. IrAEs were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Among the 38 NSCLC patients, 21 patients (55%) experienced one or more irAEs. The total number of irAEs was 33 with the majority classified as either grade 1 (n=18, 55%) or grade 2 (n=11, 33%) (Table 1). PIR-sensitive group showed longer irAE free period with the median ‘Time to first irAE' being 54 weeks compared to 9.5 weeks in PIR-not sensitive (p=0.22, HR=0.56, 95% CI=0.24-1.34). The median ‘Time to each irAE' were 45 weeks and 12 weeks in PIR-sensitive and PIR-not sensitive, respectively (p=0.1, HR=0.55, 95% CI=0.28-1.1). The median ‘Time to each irAE above grade 1' demonstrated similar results with less differences between the two groups with median values of 54 weeks and 30 weeks in PIR-sensitive and PIR-not sensitive, respectively (p=0.28, HR=0.57, 95% CI=0.21-1.56). Our results demonstrated a trend that PIR-sensitive patients are more likely to tolerate immunotherapy longer without developing irAEs. It implies the potential value of the baseline PIR test in predicting the development of irAEs and selecting subsets of patients who need close monitoring with immunotherapy. Distribution of irAEs by PIR classificationVariablesSensitiveNot-sensitiveTotal number of patients, n1325Patients without irAE, n (%)7 (54%)10 (40%)Patients with irAE, n (%)6 (46%)15 (60%)Total number of irAEs, n1023Grade 1, n (%)5 (50%)13 (57%)Grade 2, n (%)5 (50%)6 (26%)Grade 3, n (%)02 (8%)Grade 4, n (%)01 (4%)Grade 5, n (%)01 (4%) Citation Format: Myungwoo Nam, Leeseul Kim, William Cheng, William H. Bae, Jin Young Hwang, Yoonhee Choi, Yeun Ho Lee, Won Kyung Hur, Chan Mi Jung, Heayoon S. Cho, Young Kwang Chae. Potential role of serum proteome in predicting immune-related adverse events from immunotherapy in non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 520.

Role of mass spectrometry-based serum proteomics signatures in predicting clinical outcomes and toxicity in patients with cancer treated with immunotherapy

“…Thus, the PIR test may be detecting a temporal relationship between irAEs and survival, thereby identifying a patient population who are less likely to develop irAEs, without compromising on efficacy. 42 …”