Phase 1 trial of carfilzomib in relapsed/refractory peripheral T-cell lymphoma

Ann Hematol. 2022 Feb;101(2):335-340. doi: 10.1007/s00277-021-04692-9. Epub 2021 Oct 20.

Abstract

Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m2. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.

Keywords: Carfilzomib; PTCL; Phase 1 trial.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Drug Administration Schedule
  • Female
  • Humans
  • Lymphoma, T-Cell, Peripheral / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / drug therapy*
  • Oligopeptides / administration & dosage
  • Oligopeptides / adverse effects
  • Oligopeptides / therapeutic use*
  • Progression-Free Survival
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • carfilzomib