The Debut of Inflammatory Musculoskeletal Pathology in Patients Receiving Anticancer Therapy with PD-1/PD-L1 Pathway Inhibitors

Objective : to describe musculoskeletal immune-mediated adverse events (iAEs) associated with the therapy of solid tumors with immune checkpoint inhibitors (ICIs, inhibitors of the PD-1/PD-L1 pathway). Patients and methods . 13 patients receiving ICIs therapy with musculoskeletal iAEs were examined. The average age of patients was 59±10 years. All cases had a histologically verified diagnosis of a malignant solid neoplasm: melanoma (n=5), kidney cancer (n=3), bladder cancer (n=2), non-small cell lung cancer (n=1), breast cancer (n=1), cervical cancer (n=1). All patients were prescribed inhibitors of the PD-1/PD-L1 signaling pathway: nivolumab (n=6), pembrolizumab (n=3), atezolizumab (n=3), prolgolimab (n=1). In 7 (54%) patients, in addition to musculoskeletal disorders, other AEs were also detected: thyroiditis (n=3), neuropathy (n=2), rash (n=1), dry syndrome (n=1), hepatitis (n=1). The median time from the start of antitumor immunotherapy (IT) to the onset of musculoskeletal pathology was 20 [9; 48] weeks. Results and discussion . Clinical manifestations of musculoskeletal pathology included: synovitis in 9 (69%) patients, tenosynovitis in 11 (85%), enthesitis in 4 (31%), morning stiffness in the joints for more than 30 minutes in 4 (31%). In 11 cases, musculoskeletal pathology was persistent (in 9 patients with arthritis and 2 with periarthritis) and in 2 – transient. The knee (77%), shoulder (69%) and hand (54%) joints were most frequently affected, with bilateral involvement in 9 (69%) patients. Inflammatory changes in the joints were represented by mono- (n=1), oligo- (n=3) and polyarthritis (n=5), including those involving the small joints of the hands and/or feet (n=5) and predominantly affecting the joints of the lower limbs (n=3). In 3 patients with arthritis, periarticular changes dominated in clinical picture (in 2 patients with symmetrical polyarthritis and severe tenosynovitis, in another 1 patient – with RS3PE syndrome). The severity of musculoskeletal pathology was assessed using the CTCAE v5.0 toxicity criteria: grade 1 was documented in 2 (15.5%), grade 2 in 9 (69%), and grade 3 in 2 (15, 5%) patients. Laboratory workup revealed elevation of ESR ≥30 mm/h (median – 34 [14; 42] mm/h) in 7 out of 12 (58%) patients, elevation of CRP level >5 mg/l (median – 7.2 [4.6; 12.9] mg/l) – in 7 out of 10 (70%). In 7 out of 10 patients, antinuclear antibodies (Hep2) were detected in titers: 1:160 (n=2), 1:320 (n=3), 1:640 (n=2). Rheumatoid factor and an