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. 2020 Jun;22(6):919-927.
doi: 10.1007/s12094-019-02214-8. Epub 2019 Oct 1.

Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies

T Sakakida  1 , T Ishikawa  2   3 , Y Chihara  4   5 , S Harita  5 , J Uchino  5 , Y Tabuchi  4   6 , S Komori  7 , J Asai  7 , T Narukawa  8 , A Arai  9 , H Tsunezuka  10 , T Kosuga  11 , H Konishi  11 , M Moriguchi  1 , H Yasuda  1 , F Hongo  8 , M Inoue  10 , S Hirano  9 , O Ukimura  8 , Y Itoh  1 , T Taguchi  4   12 , K Takayama  5
Affiliations

Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies

T Sakakida et al. Clin Transl Oncol. 2020 Jun.

Abstract

Purpose: Immune checkpoint inhibitors (ICIs) show promising clinical activity in advanced cancers. However, the safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies (ANA) are unclear.

Methods: 191 patients treated with nivolumab, pembrolizumab, atezolizumab, or durvalumab for unresectable advanced cancers between September 2014 and December 2018 were identified retrospectively. Patients were divided into positive (ANA titers ≥ 1:160) and negative ANA groups (ANA titers < 1:160). Development of immune-related adverse events (irAEs), the overall response rate (ORR), and disease control rate (DCR) were monitored.

Results: Positive ANA titers were seen in 9 out of 191 patients. Four patients in the positive ANA group and 69 patients in the negative group developed irAEs of any grade without a significant difference between the groups. The development of endocrine, pulmonary, and cutaneous irAEs was not significant, whereas positive ANA was significantly higher in patients who developed colitis (2/9) than in patients who did not (3/182, P = 0.0002). DCR in the positive and negative ANA group was 37.5% and 67.5%, respectively, and was not statistically significant, but had better efficacy in patients without ANA (P = 0.08). ANA-related autoimmune diseases such as SLE, Sjögren's syndrome, MCTD, scleroderma, dermatomyositis, and polymyositis was not induced in either group. However, one patient with preexisting dermatomyositis had a flare up after initiation of atezolizumab.

Conclusion: Further studies to identify predictive factors for the development of irAEs are required to provide relevant patient care and maximize the therapeutic benefits of ICIs.

Keywords: Antinuclear antibodies; Autoimmune diseases; Immune checkpoint inhibitors; Immune-related adverse events; Programmed cell death 1 blockade.

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