Khalid, Ahmed Bilal

Background Patients with paraneoplastic syndromes (PNS) are excluded from clinical trials involving immune checkpoint inhibitors (ICIs) due to safety concerns. Moreover, real-world data on efficacy and safety is scarce. Methods In this retrospective study, data were collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at nine institutions. Patients were classified into: Cohort 1 (pre-existing PNS before ICI initiation), cohort 2 (PNS during ICI treatment), and cohort 3 (PNS after ICI discontinuation). Patients with metastatic non-small cell lung cancer (NSCLC) (mNSCLC) from cohort 1 were matched to patients who were PNS-free at each institution up to a 1:3 ratio for age, sex, type of ICI, use of concurrent chemotherapy, and number of lines of systemic therapy prior to ICI initiation. Kaplan-Meier method was used to assess overall survival (OS) and time-to-next treatment (TTNT). Results Among 109 patients with PNS treated with ICIs, median age at ICI initiation was 67 years (IQR: 58–74). The most represented cancer type was NSCLC (n=39, 36%). In cohort 1 (n=55), PNS exacerbations occurred in 16 (29%) patients with median time to exacerbation after ICI of 1.1 months (IQR: 0.7–3.3). Exacerbation or de novo PNS prompted temporary/permanent interruption of ICIs in 14 (13%) patients. For cohort 2 (n=16), median time between ICI initiation and de novo PNS was 1.2 months (IQR: 0.4–3.5). Treatment-related adverse events (trAEs) occurred in 43 (39%) patients. Grade ≥3 trAEs occurred in 18 (17%) patients. PNS-directed immunosuppressive therapy was required in 55 (50%) patients. We matched 18 patients with mNSCLC and PNS (cohort 1) to 40 without PNS, treated with ICIs. There was no significant difference in OS or TTNT between patients with mNSCLC with and without PNS, although a trend was seen towards worse outcomes in patients with PNS. TrAEs occurred in 6/18 (33%) and 14/40 (35%), respectively. Grade ≥3 trAEs occurred in 4 (22%) patients with PNS and 7 (18%) patients without PNS. Conclusions Exacerbations of pre-existing PNS occurred in 29% of patients treated with ICIs and both exacerbations and de novo PNS occur early in the ICI course. TrAE from ICIs were similar between patients with and without PNS. Our data suggest that pre-existing PNS should not preclude consideration of ICI therapy although patients may not derive the same clinical benefit compared with patients without PNS.

e14683 Background: Immune checkpoint inhibitors (ICIs) have altered the landscape of cancer treatment. ICIs are associated with immune mediated diarrhea and colitis (IMDC) which can be challenging to diagnose and differentiate from other etiologies of diarrhea. Clostridium difficile infection (CDI) is a common cause of diarrhea in patients with cancer and can have similar symptoms. In a similar study, CDI was found to be relatively common in ICI-treated cancer patients and especially those with IMDC requiring immunosuppressants. Our study evaluates the incidence of CDI and IMDC in patients with ICI exposure and compares clinical characteristics between the two to determine risk factors that may predispose patients to CDI or IMDC. Methods: This is a retrospective, single-center study of cancer patients on an ICI from 1/1/2011 to 4/7/2022 who were tested for Clostridium difficile with stool nucleic acid amplification tests during or after treatment with an ICI. Patients were determined to have CDI if clinically suspected and had to have a positive stool GDH Ag along with positive C. difficile toxins A & B or a positive stool C. difficile toxin B gene. Patients with positive GDH Ag in the stool but with negative toxins A&B were determined to be colonized. The diagnosis of IMDC was based on the clinical presentation and had to be made by the treating oncologist. Results: 375 patients met our study criteria and got CDI testing at any point during or after ICI exposure. 27 patients tested positive for CDI, whereas 24 were colonized. 105 patients were determined to have IMDC and 97/105 received treatment with steroids or immunosuppressants. Among patients determined to have IMDC, 6 were colonized for clostridium difficile. There were no patients with IMDC who were also positive for clostridium difficile. 71 patients were on a dual ICI regimen whereas 304 patients were on a single ICI. In patients on the dual ICI regimen, 67.6% were diagnosed with IMDC when compared to patients on a single ICI regimen where 18.8% of patients were diagnosed with IMDC (p<0.0001). The absolute lymphocyte count on the day of CDI testing was 1.185 ± 0.066 in the IMDC group when compared to 0.948 ± 0.044 in the non-IMDC group (p=0.003). The mean duration of diarrhea was longer in the IMDC group at 16.905 ± 1.211 days when compared to the CDI group at 9.852 ± 2.387 days (p= 0.0094). Smoking status, sex, history of autoimmunity, and history of prior immune related adverse events did not impact incidence of IMDC or CDI. Conclusions: IMDC was a common cause of diarrhea in patients with ICI exposure who were tested for CDI. We did not find IMDC to be a risk factor for CDI. IMDC has a longer duration of diarrhea and colitis symptoms when compared to CDI. The absolute lymphocyte count on symptom onset is higher in patients with IMDC when compared to patients with CDI and may be useful in identifying patients with IMDC earlier.