Higgins, Alexandra

8030 Background: There is growing interest in the identification of modifiable patient-specific factors that may predict response to immune checkpoint inhibitors (ICIs) in classical Hodgkin lymphoma (cHL). Recently, it has been proposed that antibiotic use could decrease the efficacy of ICIs in the treatment of advanced solid malignancies. The objective of our study is to assess whether antibiotic use prior to or concurrent with ICIs is associated with changes in outcomes in patients with cHL. Methods: Patients who received a PD-1 or CTLA-4 blocker for the treatment of cHL at Mayo Clinic Rochester between January 1, 2011 and October 20, 2018 were identified. We conducted a longitudinal retrospective chart review to identify those who received antibiotics within 30 or 90 days prior to initiation or concurrent with ICI therapy. Univariate cox regression analysis was used to assess for an association between antibiotic use and overall survival (OS) and progression-free survival (PFS) within these groups; a time-dependent variable was used for concurrent antibiotic use. Results: A total of sixty-two patients were identified (61% male, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 38 months (range: 4-78). Twenty-one patients (34%) received antibiotics within 90 days of initiation of ICI, of which thirteen (21%) received antibiotics within 30 days. Thirty-five patients (57%) received antibiotics concurrently with ICI. Concurrent and prior antibiotic use within 90 days of ICI were both associated with inferior PFS (concurrent HR = 6.38 [95% CI 3.02-13.47]; 90-day HR = 2.21 [95% CI 1.10-4.47]) and OS (concurrent HR = 8.77 [95% CI 1.91-40.36]; 90-day HR = 2.96 [95% CI 1.09-8.04]). Conclusions: Antibiotic use is associated with inferior outcomes in patients with cHL treated with ICIs in this single institution cohort. This may reflect potential antibiotic effects on the gut microbiome (GMB) and immune system as has been suggested in prior studies. Further confirmatory studies and examination of potential confounding covariates are needed.

95 Background: The incidence of immune-related adverse events (irAEs) in patients (pts) with Hodgkin lymphoma (HL) treated with PD-1 antibodies (ICI) is reported at 28 - 36%. However, clinically relevant information on irAE onset, duration, or impact on ability to continue therapy in HL is lacking. Additionally, these incidence rates reflect CTCAE definition and grading, and not ASCO Clinical Practice Guidelines irAE-specific criteria (Brahmer et al, JCO 2018). The objectives of this study were to evaluate the rate and severity of irAEs in HL pts using ASCO criteria, to characterize irAE time profile and to assess their impact on continued therapy. Methods: HL pts who received a PD-1 inhibitor for the treatment of HL at Mayo Clinic Rochester between January 1, 2011 and March 1, 2018 were identified. We conducted a detailed, longitudinal retrospective chart review with definition and grading of irAEs in accordance with ASCO guidelines. Results: Fifty-one pts were identified (35% women, median age at ICI initiation 35 years [range: 19-87]). Median duration of follow up from ICI start was 30 months (range: 1-70). Thirty-one pts (61%) had any irAE. Most common irAEs were inflammatory/bullous dermatoses (23.5%/5.9% any grade/grade3-4; median onset/duration of 81/57 days[d]), followed by thyroiditis (22%/0%; 86/84 d), colitis (14%/8%; 82/106 d), pneumonitis (14%/10%; 241/182 d), and hepatitis (14%/4%; 71/35 d). Fifteen pts (29%) required treatment with steroids. Among the total cohort, ICI was held for an irAE 28 times (50% of 56 total irAEs). Median treatment cycles held was 2.5 and ICI was permanently discontinued due to irAE in 18%. The most common irAE leading to treatment discontinuation was pneumonitis, followed by neuritis (5.9%/3.9%; 179/374 d), colitis, and rash. Conclusions: The rate of irAEs of 61% in this cohort as defined by ASCO consensus criteria was higher than reported in trials. Most irAEs were characterized by delayed onset of several months and prolonged duration, particularly pneumonitis and neuritis. Treatment discontinuation due to irAEs was infrequent overall. Further studies are needed to determine whether the development or duration of irAEs is predictive of treatment outcomes in HL.