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448 Clinical outcomes and safety of immune checkpoint inhibitors (ICI) in patients with solid tumors and paraneoplastic syndromes (PNS)
  1. Amin Nassar1,
  2. Talal El Zarif2,
  3. Ahmed Bilal Khalid3,
  4. Serena J Rahme4,
  5. Lucia Kwak2,
  6. Marita Salame4,
  7. Elias Bou Farhat2,
  8. Edward El Am4,
  9. Arjun Ravishankar1,
  10. Bachar Ahmad1,
  11. Frank Aboubakar Nana5,
  12. David Kaldas6,
  13. Abdul Rafeh Naqash7,
  14. Elad Sharon8,
  15. Nicole R Leboeuf2,
  16. Alessio Cortellini9,
  17. Andrea Malgeri9,
  18. Shruti Gupta10,
  19. Jeffrey A Sparks10,
  20. Jenny Linnoila11,
  21. Ole-Petter R Hamnvik10,
  22. Kaushal Parikh4,
  23. Rana McKay12,
  24. Thomas Dilling6,
  25. Toni K Choueiri2,
  26. Elio Adib10,
  27. Elie Najem11,
  28. So Yeon Kim5 and
  29. Guru P Sonpavde13
  1. 1Yale University New Haven Hospital, New Haven, CT, USA
  2. 2Dana Farber Cancer Institute, Boston, MA, USA
  3. 3Indiana University, Indianapolis, IN, USA
  4. 4Mayo Clinic, Rochester, MN, USA
  5. 5UC Louvain, Louvain-la-Neuve, Belgium, Belgium
  6. 6Moffitt Cancer Center, Tampa, FL, USA
  7. 7Stephenson Cancer Center Oklahoma University, Greenville, NC, USA
  8. 8National Institutes of Health, Bethesda, MD, USA
  9. 9Fondazione Policlinico Universitario Campus Bio-Medico, Roma, Rome, Italy
  10. 10Brigham and Women’s Hospital, Boston, MA, USA
  11. 11Massachusetts General Hospital, Boston, MA, USA
  12. 12Moores Cancer Center, University of California San Diego, La Jolla, CA, USA
  13. 13Advent Health Cancer Institute, Orlando, FL, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.


Background Patients 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.

Methods Data 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.

Results Among 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.

Conclusions Among patients with PNS, ICIs appeared to be tolerated, albeit with a high rate of worsening of pre-existing PNS. In the matched cohort of patients with NSCLC with and without PNS, the clinical outcomes and safety profiles were similar.

Ethics Approval This study is approved by the institutional review board (IRB) at DFCI and local IRBs at participating centers per institutional policy and the Declaration of Helsinki.

Abstract 448 Figure 1

Kaplan-meier analysis of (A) overall survival and (B) time to treatment failure between patients with and without PNS with metastatic non-small cell lung cancer in matched population.

Abstract 448 Table 1

Baseline characteristics of patients with solid tumors and PNS

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