Clinical outcomes and safety of immune checkpoint inhibitors in patients with solid tumors and paraneoplastic syndromes.

Abstract

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.

• Authors: Amin H Nassar, Talal El Zarif, Ahmed Bilal Khalid, Serena Rahme, Caiwei Zhong, Lucia Kwak, Marita Salame, Elias Bou Farhat, Dory Freeman, Edward El-Am, Arjun Ravishankar, Bachar Ahmad, Frank Aboubakar Nana, David Kaldas, Abdul Rafeh Naqash, Elad Sharon, Nicole R LeBoeuf, Alessio Cortellini, Andrea Malgeri, Shruti Gupta, Ahmad Al-Hader, Jeffrey A Sparks, Jenny Linnoila, Ole-Petter R Hamnvik, Tarek H Mouhieddine, Thomas Marron, Kaushal Parikh, Rana R McKay, Thomas Dilling, Toni K Choueiri, Elio Adib, Elie Najem, So Yeon Kim, Guru Sonpavde
• Journal: Journal for immunotherapy of cancer (J Immunother Cancer) Vol. 12 Issue 3 (Mar 05 2024) ISSN: 2051-1426 [Electronic] England
• PMID: 38448038 (Publication Type: Journal Article)
• Copyright: © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Immune Checkpoint Inhibitors

Topics

• Humans
• Middle Aged
• Aged
• Immune Checkpoint Inhibitors (adverse effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Retrospective Studies
• Lung Neoplasms (drug therapy)
• Paraneoplastic Syndromes (drug therapy, etiology)