Pralatrexate in Chinese Patients with Relapsed or Refractory Peripheral T-cell Lymphoma: A Single-arm, Multicenter Study

Target Oncol. 2019 Apr;14(2):149-158. doi: 10.1007/s11523-019-00630-y.

Abstract

Background: Peripheral T-cell lymphoma (PTCL) is associated with poor prognosis, particularly in patients with relapsed/refractory (R/R) disease. Pralatrexate, a folate analogue inhibitor, was the first drug approved to treat R/R PTCL.

Objective: As the distribution of PTCL subtypes differs between populations and few patients in the pivotal trial of pralatrexate were Asian, this study investigated the safety and efficacy of pralatrexate as monotherapy in Chinese patients with R/R PTCL.

Patients and methods: In this single-arm, open-label, multicenter study, 71 patients with R/R PTCL (median [range] 2 [1-14] prior systemic treatments) were recruited from 15 centers in China and received pralatrexate IV 30 mg/m2/week for 6 weeks in 7-week cycles (with vitamin B12/folate). The primary endpoint was objective response rate (ORR) per central review (null hypothesis: ORR < 15%).

Results: The study's primary objective was met: ORR (95% CI) was 52% (40-64%) (p < 0.001) and responses were observed across pre-specified patient subgroups. Median (95% CI) duration of response was 8.7 (3.3-14.1) months and first response was observed in Cycle 1 for most (84%) patients. Median (95% CI) progression-free survival and overall survival was 4.8 (3.1-8.1) months and 18.0 (10.4-NA) months, respectively. The most common treatment-emergent adverse events were stomatitis (68% [Grade 3/4: 20%]), anemia (49% [Grade 3/4: 24%]) and alanine aminotransferase increase (41% [Grade 3/4: 4%]).

Conclusions: These results demonstrate that pralatrexate may represent a promising treatment option for Chinese patients with R/R PTCL. The ORR of 52% compared favorably with prior studies of pralatrexate in other populations and there were no unanticipated side effects.

Trial registration: ClinicalTrials.gov identifier: NCT03349333.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aminopterin / analogs & derivatives*
  • Aminopterin / therapeutic use
  • Drug Resistance, Neoplasm / drug effects*
  • Female
  • Folic Acid Antagonists / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Lymphoma, T-Cell, Peripheral / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Salvage Therapy*
  • Survival Rate
  • Young Adult

Substances

  • 10-propargyl-10-deazaaminopterin
  • Folic Acid Antagonists
  • Aminopterin

Associated data

  • ClinicalTrials.gov/NCT03349333