1047P - Tocilizumab is an effective secondary prophylaxis during immune checkpoint inhibitor rechallenge following arthritis

Background

Arthritis represents a frequent irAE often leading to the discontinuation of treatment and the initiation of immunosuppressive therapy. The efficacy of tocilizumab, in the treatment of arthritis and as a prophylactic strategy in case of re-exposure to ICIs remains to be elucidated.

Methods

The objective of this single-center study was to assess the efficacy of tocilizumab in the treatment of arthritis and its potential use as secondary prophylaxis during ICI re-challenge. A total of 27 arthritis (n=27) treated at the CHUV between 2020 and 2023 were included in the study. Tocilizumab was administered at a dose of 8 mg/kg every two weeks, concurrently with prednisone dosing at 0.3 mg/kg. This treatment was maintained until the resolution of the arthritis and the complete tapering of steroids and concomitantly to ICI treatment in case of prophylaxis.

Results

Median age of the patients was 70 years. Median time for arthritis diagnosis was 165 days. The ICI regimens included anti-PD-(L)1 in 17 patients (63%), anti-PD-1 plus anti-CTLA4 in 9 patients (33%), anti-PD-1 plus with anti-LAG3 therapy in 1 patient (4%). Among the 21 patients treated with tocilizumab for arthritis, the ACR70 response rate (>70% improvement) was 100% at 10 weeks. A total of 81% (n=13) of patients achieved steroid-free remission after 24 weeks on tocilizumab. Tocilizumab was continued during ICI rechallenge in 12 patients. ICI rechallenge included anti-PDL-(L)1 in 7 (47%), anti-PD-1 and plus CTLA4 in 6 (40%) and anti-PD-1 plus anti-LAG3 therapy in 2 patient (13%). There were no ICI-related arthritis flares or steroid need. Six months after ICI rechallenge combined with tocilizumab prophylaxis, the ORR was 40%.

Conclusions

Tocilizumab is an effective treatment for arthritis. Its concurrent administration during ICI rechallenge effectively prevents the recurrence of arthritic symptoms and ICI discontinuation, enabling the sustained rechallenge of ICI without the recurrence of arthritic symptoms, the requirement for the initiation of steroid. This strategy may serve to diminish the exposure to steroids, as well as to prolong the duration of ICI treatment and maximize its benefit, while enhancing the adherence of patients undergoing ICI rechallenge.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

CHUV.

Disclosure

M. Obeid: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Moderna; Financial Interests, Speaker, Consultant, Advisor: Roche. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GSK, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, Prime, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, BMS, AstraZeneca, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology and Deputy Editor Lung Cancer: Elsevier; Financial Interests, Institutional, Advisory Board, Permanent independent scientific advisor: Hutchmed; Financial Interests, Institutional, Member of Board of Directors, Swiss network of pharmacies: Galenica; Financial Interests, Institutional, Coordinating PI, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Steering Committee Member, RELATIVITY 095: BMS; Financial Interests, Institutional, Steering Committee Member, BGB-A317-A1217-301/AdvanTIG-301: BeiGene; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Steering Committee Member, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Steering Committee Member, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Steering Committee Member, LAGOON: PharmaMar; Financial Interests, Institutional, Steering Committee Member, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Trial Chair, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Steering Committee Member, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Officer: ESMO President 2020-2022; Non-Financial Interests, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Principal Investigator, Involved in academic trials: ETOP/EORTC/SAKK; Non-Financial Interests, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Leadership Role, Past-President: ESMO; Non-Financial Interests, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Leadership Role, Vice-resident: SAMO; Non-Financial Interests, Member, Association of Swiss Interns and Residents: ASMAC/VSAO. All other authors have declared no conflicts of interest.