Combination of mitoxantrone hydrochloride liposome with cyclophosphamide, vincristine, and prednisone for patients with treatment-naive peripheral T-cell lymphoma: A multicenter, open-label, single-arm, phase 1b trial.

Abstract

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphomas. Most subtypes are generally associated with a poor prognosis when treated with standard chemotherapy. This study enrolled patients with untreated PTCL who received mitoxantrone hydrochloride liposome (Lipo-MIT) plus cyclophosphamide, vincristine, and prednisone (CMOP) every 4 weeks for six cycles. The study consisted of a 3 + 3 dose-escalation phase (Lipo-MIT at 12, 15, 18, and 21 mg/m²) and a specific dose-expansion phase (Lipo-MIT at the recommended phase 2 dose [RP2D]). Between December 21, 2020, and November 17, 2022, 38 patients were enrolled. No dose-limiting toxicities were reported, and the RP2D was established at 18 mg/m². Grade ≥3 treatment-related adverse events occurred in 33 (86.8%) patients, with the most common being neutrophil count decrease (76.3%) and white-cell count decrease (73.7%). No treatment-related deaths occurred. Among the 35 response-evaluable patients, the independent review committee-assessed complete response rate (CRR) was 54.3% (95% CI, 36.6%-71.2%), and the overall response rate (ORR) was 88.6% (95% CI, 73.3%-96.8%). For the 17 patients treated at RP2D, the CRR, ORR, median duration of CR, and median duration of response were 64.7% (95% CI, 38.3%-85.8%), 94.1% (95% CI, 71.3%-99.9%), 28.0 (95% CI, 9.8-46.3) months, and 28.0 (95% CI, 4.0-52.1) months, respectively. At a median follow-up of 23.8 months, the median progression-free survival was 20.8 (95% CI, 6.1-35.5) months, and the median overall survival was not reached. Lipo-MIT exhibited a favorable pharmacokinetics (PK) profile. The CMOP regimen demonstrates a favorable PK profile, a manageable safety profile, and encouraging preliminary antitumor activity.