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

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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.

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Abbreviations

ICI:

Immune checkpoint inhibitors

PD-1:

Programmed cell death protein 1

PD-L1:

Programmed cell death ligand 1

NSCLC:

Non-small cell lung cancer

MM:

Malignant melanoma

irAEs:

Immune-related adverse events

CTLA-4:

Cytotoxic T-lymphocyte-associated protein 4

ANA:

Antinuclear antibodies

PFS:

Progression-free survival

OS:

Overall survival

ORR:

Overall response rate

DCR:

Disease control rate

PS:

Performance status

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Funding

No donations or supports exist for this study.

Author information

Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji agaru, Kawaramachi Street, Kamigyoku, Kyoto, 602-8566, Kyoto, Japan

    T. Sakakida, T. Ishikawa, M. Moriguchi, H. Yasuda & Y. Itoh

  2. Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan

    T. Ishikawa, Y. Chihara, Y. Tabuchi & T. Taguchi

  3. Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Y. Chihara, S. Harita, J. Uchino & K. Takayama

  4. Department of Dermatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    S. Komori & J. Asai

  5. Department of Urology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    T. Narukawa, F. Hongo & O. Ukimura

  6. Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    A. Arai & S. Hirano

  7. Division of Thoracic Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    H. Tsunezuka & M. Inoue

  8. Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    T. Kosuga & H. Konishi

  9. Division of Endocrine and Breast Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    T. Taguchi

  10. Department of Hospital Pharmacy, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Y. Tabuchi

Authors
  1. T. Sakakida
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  2. T. Ishikawa
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  3. Y. Chihara
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  4. S. Harita
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  7. S. Komori
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Contributions

TS, TI, YI and KT were responsible for the design of the study, selection and analysis and interpretation of the data. They also have revised critically the manuscript for important intellectual content. TI, YC, SH, JU, YT, SK, JA, TN, AA, HT, TK, HK, MM, HY, FH, MI, SH, OU, TT and KT were responsible for the acquisition and clinical interpretation of the data. All authors had full access to all of the data in the study and had final responsibility for the decision to submit for publication.

Corresponding author

Correspondence to T. Ishikawa.

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Conflict of interest

The authors declare that they have no conflict of interest. No donations or supports exist for this study.

Ethical approval

The study was designed under the responsibility of Kyoto Prefectural University of Medicine, in conjunction with the steering committee.

Informed consent

Given the retrospective nature of this work, informed consent was waived for the individual participants included in the study in accordance with the standards of the Kyoto Prefectural University of Medicine Institutional Medical Ethics Review Committee.

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Sakakida, T., Ishikawa, T., Chihara, Y. et al. Safety and efficacy of PD-1/PD-L1 blockade in patients with preexisting antinuclear antibodies. Clin Transl Oncol 22, 919–927 (2020). https://doi.org/10.1007/s12094-019-02214-8

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  • DOI: https://doi.org/10.1007/s12094-019-02214-8

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