Identification of a biomarker for anti-PD1 antibody-related clinical effect based on the measurement of quantitative and qualitative change of T cells

• Project/Area Number: 17K15506
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: The University of Tokushima
• Principal Investigator: OKADA Naoto 徳島大学, 病院, 薬剤師 (30623269)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 抗PD1抗体 / 個別化投与法 / 免疫関連有害事象 / 末梢血リンパ球 / 治療効果 / 個別化医療 / 医療薬学 / 抗PD-1抗体 / バイオマーカー

Outline of Final Research Achievements

The aim of this study was to identify a biomarker for anti PD1 antibody-related clinical effect based on the measurement of quantitative and qualitative change of T cells. We conducted a multicenter retrospective study to explore the biomarker to predict the clinical effect and immune-related adverse events induced by nivolumab, anti-PD1 antibody. We identified the increase in baseline peripheral lymphocyte count at the time of onset of irAEs was significantly greater in the irAEs-positive group than in the irAEs-negative group after 4 cycles of nivolumab treatment. Our multicenter retrospective study also clarified the dichotomous relationship between irAEs induced by nivolumab in early phase and clinical efficacy in melanoma patients. These results indicated that the early detection of irAEs based on lymphocyte count monitoring and adequate management of irAEs would allow achieving the maximum clinical response with nivolumab treatment in melanoma patients.

Academic Significance and Societal Importance of the Research Achievements

抗PD1抗体の治療を最適化するためには、臨床現場で応用可能な治療効果予測バイオマーカーが必要になる。本解析から末梢血リンパ球の量的変化を指標にすることで抗PD1抗体薬による免疫関連有害事象を早期に予測することが可能であることが示された。末梢血リンパ球数の測定には特別な検査機器は必要なく、臨床応用性が高いバイオマーカーである。そのため、本解析により得られた知見は、応用性の高い知見であり、臨床に即座に還元可能である。

Research Products

• [Journal Article] Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study (2019)
  • Author(s): Okada Naoto、Kawazoe Hitoshi、Takechi Kenshi、Matsudate Yoshihiro、Utsunomiya Ryo、Zamami Yoshito、Goda Mitsuhiro、Imanishi Masaki、Chuma Masayuki、Hidaka Noriaki、Sayama Koji、Kubo Yoshiaki、Tanaka Akihiro、Ishizawa Keisuke
  • Journal Title: Clinical Therapeutics Volume: 41 Issue: 1 Pages: 59-67
  • DOI: 10.1016/j.clinthera.2018.11.004
  • Peer Reviewed / Open Access
• [Journal Article] Pharmacovigilance evaluation of the relationship between impaired glucose metabolism and BCR-ABL inhibitor use by using an adverse drug event reporting database (2018)
  • Author(s): Okada Naoto、Niimura Takahiro、Zamami Yoshito、Hamano Hirofumi、Ishida Shunsuke、Goda Mitsuhiro、Takechi Kenshi、Chuma Masayuki、Imanishi Masaki、Ishizawa Keisuke
  • Journal Title: Cancer Medicine Volume: 8 Issue: 1 Pages: 174-181
  • DOI: 10.1002/cam4.1920
  • NAID: 120006894607
  • Peer Reviewed / Open Access
• [Presentation] ニボルマブによる免疫関連有害事象の発現予測バイオマーカーの探索：多施設共同後ろ向き研究による検討 (2018)
  • Author(s): 岡田直人, 河添仁, 武智研志, 座間味義人, 今西正樹, 中馬真幸, 飛鷹範明, 桐野靖, 中村敏己, 寺岡和彦, 田中亮裕, 石澤啓介
  • Organizer: 医療薬学フォーラム 2018・第26回クリニカルファーマシーシンポジウム
• [Presentation] 発現予防を主体とした副作用マネージメントの構築に向けた臨床薬学研究の展開 (2018)
  • Author(s): 岡田 直人
  • Organizer: 第28回日本医療薬学会年会 シンポジウム