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448 Clinical outcomes and safety of immune checkpoint inhibitors (ICI) in patients with solid tumors and paraneoplastic syndromes (PNS)

BackgroundPatients with PNS are frequently excluded from clinical trials involving ICIs due to safety concerns. Herein, we study the safety and clinical outcomes of ICIs in patients with solid tumors and PNS.MethodsData was collected on patients with PNS and solid tumors receiving ICI between 2015 a...

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Published in:Journal for immunotherapy of cancer 2023-11, Vol.11 (Suppl 1), p.A498-A498
Main Authors: Nassar, Amin, Zarif, Talal El, Khalid, Ahmed Bilal, Rahme, Serena J, Kwak, Lucia, Salame, Marita, Farhat, Elias Bou, Am, Edward El, Ravishankar, Arjun, Ahmad, Bachar, Nana, Frank Aboubakar, Kaldas, David, Naqash, Abdul Rafeh, Sharon, Elad, Leboeuf, Nicole R, Cortellini, Alessio, Malgeri, Andrea, Gupta, Shruti, Sparks, Jeffrey A, Linnoila, Jenny, Hamnvik, Ole-Petter R, Parikh, Kaushal, McKay, Rana, Dilling, Thomas, Choueiri, Toni K, Adib, Elio, Najem, Elie, Kim, So Yeon, Sonpavde, Guru P
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Language:English
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Summary:BackgroundPatients with PNS are frequently excluded from clinical trials involving ICIs due to safety concerns. Herein, we study the safety and clinical outcomes of ICIs in patients with solid tumors and PNS.MethodsData was collected on patients with PNS and solid tumors receiving ICI between 2015 and 2022 at 7 institutions. A panel of 22 different PNS was predefined and PNS confirmed by specialists were included. Patients were classified into: Cohort 1 (PNS pre-ICI initiation); Cohort 2 (PNS post-ICI initiation). To evaluate the impact of PNS on clinical outcomes, patients with metastatic non-small cell lung cancer (mNSCLC) from both cohorts were matched to patients with mNSCLC and without PNS at each institution up to a 1:3 ratio by (1)age, (2)sex, (3)ICI class, (4)concurrent chemotherapy, and (5)number of prior systemic therapies.Overall survival (OS) and time to treatment failure (TTF) were estimated using the Kaplan-Meier method. Distributions were compared between patients with and without PNS using a log rank. Treatment-related adverse events (trAEs) were reported per Common Terminology Criteria for Adverse Events v5.0.ResultsAmong 99 patients with PNS treated with ICIs, median follow-up time was 34 months. The most represented cancer type was NSCLC (n=37,37%,table 1). 15/30 patients with neurologic PNS had neural autoantibodies. In Cohort 1(n=49), PNS worsened in 14(29%) patients after a median time of 1.6 months (IQR:0.6–4.0) following ICI initiation. For Cohort 2 (n=50), median time between ICI initiation and onset of new PNS was 3.8 months (IQR:1.3–10.3). In the overall cohort, trAEs occurred in 37(37%) and grade ≥3 trAEs occurred in 15 (15%) patients. The exacerbation or new diagnosis of PNS prompted temporary/permanent interruption of ICI in 14(14%) patients of which 6/14(43%) had neurologic PNS. 52(53%) patients required PNS-directed immunosuppressive therapy.We then matched 31 patients with mNSCLC and PNS from Cohorts 1 and 2 to 79 without PNS, treated with ICIs. There was no significant difference in OS or TTF between patients with mNSCLC with and without PNS (figure 1), and the prevalence of trAEs was similar between both groups. Any grade trAEs occurred in 10/31(32%) patients with PNS vs. 31/79(39%) without PNS, while grade≥3 trAEs occurred in 3(9.7%) vs. 14(18%) patients, respectively.ConclusionsAmong patients with PNS, ICIs appeared to be tolerated, albeit with a high rate of worsening of pre-existing PNS. In the matched cohort of patie
ISSN:2051-1426
DOI:10.1136/jitc-2023-SITC2023.0448