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

Background 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. Methods 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/m 2 ) and a specific dose‐expansion phase (Lipo‐MIT at the recommended phase 2 dose [RP2D]). Results 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/m 2 . 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. Conclusion The CMOP regimen demonstrates a favorable PK profile, a manageable safety profile, and encouraging preliminary antitumor activity.