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

• Published in: Annals of hematology Vol. 101; no. 2; pp. 335 - 340
• Main Authors: Krishnan, Mridula, Bociek, R. Gregory, Fanale, Michelle, Iyer, Swaminathan P., Lechowicz, Mary Jo, Bierman, Philip J., Armitage, James O., Lunning, Matthew, Kallam, Avyakta, Vose, Julie M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.02.2022; Springer Nature B.V
• Subjects: Adult; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Drug Administration Schedule; Female; Hematology; Humans; Inhibitor drugs; Lymphoma; Lymphoma, T-Cell, Peripheral - drug therapy; Male; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Oligopeptides - administration & dosage; Oligopeptides - adverse effects; Oligopeptides - therapeutic use; Oncology; Original Article; Patients; Progression-Free Survival; Targeted cancer therapy; Treatment Outcome; Carfilzomib; PTCL; Phase 1 trial
• ISSN: 0939-5555; 1432-0584; 1432-0584
• DOI: 10.1007/s00277-021-04692-9

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/m 2 . 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.