Clinical Features, Pathological Features, and Treatment Outcomes of 22 Patients with Aggressive Adult T-cell Leukemia-lymphoma Treated with a Humanized CCR4 Antibody (Mogamulizumab) at a Single Institution during a 6-year Period (2012-2018)

Intern Med. 2019 Aug 1;58(15):2159-2166. doi: 10.2169/internalmedicine.2513-18. Epub 2019 Apr 17.

Abstract

Objective To elucidate the clinical impact of humanized CCR4 antibody (mogamulizumab) on adult T-cell leukemia-lymphoma (ATL), we retrospectively analyzed the clinical and pathological features and treatment outcomes of aggressive ATL. Methods Twenty-two patients (median age: 65 years) with aggressive ATL [acute- (n=16) or lymphoma-type (n=6)] had their characteristics analyzed. All cases were treated with mogamulizumab at our institution from 2012 to 2018. In addition, we subjected 14 specimens of ATL to histological, immunological, and genetic analyses. Results Regarding the patient outcomes, the overall response rates were 68.1% and 31.8% after 4 and 8 courses (or after the final courses), respectively. The median overall survival (OS) was 95.5 days, while the OS rates at 6 and 12 months were 31.5% and 21.1%, respectively. Concerning patient pathological characteristics, 6 of the 14 patients examined (42.9%) had CCR4 mutations. Regarding the clinicopathological findings related to the mogamulizumab response, notably, the cases with somatic CCR4 mutation tended to have a poorer response (16.7%) than those with wild-type CCR4 (62.5%) after 4 cycles of mogamulizumab. Furthermore, the CCR4 global score tended to be higher in the responder cases than in the non-responder cases. Conclusion The present findings suggest that the CCR4 expression may be related to the mogamulizumab response, although no other significant predictive markers were identified in this study. Further studies will be needed in order to identify more markers related to the mogamulizumab response.

Keywords: ATL; NS mutation and FS mutation; mogamulizumab; overall response rate; overall survival; somatic CCR4 mutation.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Female
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / drug therapy*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Survival Rate
  • Time Factors
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • mogamulizumab