Background/Purpose:

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 (anti-PD 1) antibodies, are established therapies for advanced malignancies, including melanoma, and non-small cell lung cancer (NSCLC). The adverse event (AE) profile of anti-PD 1 antibodies includes immune-related adverse events (irAEs) spanning several organ systems, many of which have defined management pathways. However, no consensus exists for the management of rheumatological (Rh) irAEs, including inflammatory arthritis, PMR and myositis, which affect 5-10% of patients receiving anti-PD 1 antibodies. Equally, there is a paucity of data presenting management options for flares of pre-existing rheumatic disease whilst undertaking anti-PD 1 therapy.

Methods:

We conducted a single centre retrospective study of patients treated with anti-PD 1 antibodies pembrolizumab (P) and nivolumab (N), who developed Rh irAEs, experienced flares of existing rheumatic disease, or experienced stability of existing rheumatic disease. Clinical and demographic data were obtained, including anti-PD 1 response (timing, durability and reason for cessation), rheumatologic presentation (including temporal relationship to anti-PD 1 therapy), rheumatologic treatment and response.

Results:

Eighteen patients (12 male, 6 female; median age 71.5 years) were included. All had metastatic malignancy (14 melanoma, 2 NSCLC, 2 head and neck squamous cell carcinoma). Anti-PD1 monotherapy (P or N) was used in 17 patients, 1 of whom had previously received the anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA4) antibody ipilimumab (I). One patient received combination N-I.

Thirteen patients developed de novo Rh irAEs (7 inflammatory arthritis, 1 PMR, 4 myositis, 1 fasciitis). Three experienced flare of Rh disease (all PMR). Two patients had no flare of their existing Rh disease (1 PMR, 1 with JIA/SSc). The median time to Rh irAE was 10.9 weeks (range 0.7-113). All myositis cases manifested within 4 weeks.

Twelve of the 16 irAEs required prednisone, all at doses ≥10mg/day. DMARDs were used in 5 cases, including HCQ in 4, MTX in 1, and SSZ in 1. One case received intravenous immunoglobulin.

Of the 18 patients, 7 completely responded to anti-PD 1, 7 partially responded, 3 had stable disease, and 1 progressive disease. Responses have been maintained despite Rheumatologic therapy. Median duration of response has not been reached.

Conclusion:

Rh irAEs to anti-PD 1 therapy present a new challenge for Rheumatologists and Oncologists. Both de novo disease, and flare, can occur. Our cohort demonstrated a high rate of response to anti-PD 1 therapy, including when Rheumatologic therapy was initiated. Prospective analysis is required to further characterise this set of diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatological-immune-related-adverse-events-in-malignancy-patients-treated-with-anti-programmed-cell-death-pd-1-antibodies/