Abstract 1685P
Background
Immune checkpoint inhibitors (ICIs) may induce serious and even lethal immune related (ir) adverse events (AEs) in any organ. The pathophysiology underlying ir-AEs is not fully explained, however, increased production of proinflammatory cytokines such as interleukin (IL)-6, has a central role. This study investigated the efficacy of the IL-6 receptor antibody tocilizumab (TCZ), for the treatment of ir-arthritis and ir-colitis among cancer patients treated with ICI.
Methods
This was a single-center interventional study (NCT03601611) with a Simon’s 2-stage optimal design. Patients with solid tumors who were treated with ICIs and had grade >1 ir-arthritis and/or ir-colitis based on Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0 were eligible for inclusion. Systemic glucocorticoids (GCs) or other immunosuppressive drugs were not allowed within a 14-day screening period. Patients were assigned to TCZ 8 mg/kg every 4 weeks. Primary endpoint was rate of ≥1 CTCAE grade improvement within 8 weeks. Secondary endpoints included safety, rate of ≥1 CTCAE grade improvement without use of GCs and rate of GC-free remission at week 24. Exploratory analyses included investigation of radiographic, endoscopic and histologic features, and cytokines.
Results
Between Jan 2019 and Feb 2020, 19 patients (ir-arthritis (n=9), ir-colitis (n=8) or both (n=2)) were included and received at least one dose of TCZ. Fourteen patients had grade 2 and 5 patients had grade 3 ir-arthritis or biopsy-confirmed ir-colitis. Some had been treated with GCs (n=8) or infliximab (n=2) previously. Ten patients continued to receive ICIs after TCZ initiation. At 8 weeks, 15/19 (79%) of patients (ir-arthritis (n=7), ir-colitis (n=6) or both (n=2)) had ≥1 grade improvement and 2 patients had stable symptoms. At 24 weeks, 13 patients had ongoing improvement without GCs, including complete remission in 10 patients. Four patients had grade 3–4 treatment-related AEs which were manageable and reversible.
Conclusions
TCZ showed promising clinical efficacy and manageable safety in treatment of ir-arthritis and/or ir-colitis. Randomized trials are warranted.
Clinical trial identification
NCT03601611.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
BMS provided support to translational analyses.
Disclosure
I.M. Svane: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Personal, Principal Investigator: Roche. All other authors have declared no conflicts of interest.