Combination of mitoxantrone hydrochloride liposome with cyclophosphamide, vincristine, and prednisone (CMOP) for patients with treatment-naïve peripheral T-cell lymphomas (PTCLs): Extended follow-up analysis of a multicenter, open-label, single-arm, phase Ib study.

Abstract

7048 Background: PTCLs represent a heterogeneous group of lymphomas generally majority of patients (pts) associated with a poor prognosis when treated with CHOP based therapy. Mitoxantrone hydrochloride liposome (Lipo-MIT) has demonstrated efficacy in relapsed/refractory PTCLs in our previous study. This study previously reported that CMOP regimen exhibits encouraging efficacy in treatment-naïve (TN) PTCLs. Here we present extended follow-up data of the final dose (NCT04548700). Methods: Eligible pts were aged 18-70 years with histologically confirmed TN PTCLs. Pts received Lipo-MIT combined with standard doses of COP regimen every four 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]). The primary endpoints were dose-limiting toxicity (DLT) and safety. Secondary endpoints included objective response rate (ORR) assessed by an independent review committee (IRC), duration of CR (DoCR), DoR, PFS, OS, and pharmacokinetics (PK). Results: As of November 17, 2022,38 pts were enrolled (26 in the dose-escalation) from 7 centers in China, including 21 (55.3%) AITL, 6 (15.8%) PTCL-NOS, 4 (10.5%) ALK- ALCL, 3 (7.9%) ALK+ PTCL, and 4 (10.5%) other types,16 (42.1%) pts had stage IV disease. No DLTs were observed and a Lipo-MIT dose of 18 mg/m 2 was recommended as the RP2D. The most common treatment-related grade 3/4 adverse events were hematologic toxicities, including neutropenia (76.3%), leukopenia (73.7%), lymphopenia (44.7%), thrombocytopenia (15.8%) and anemia (13.2%). After a median follow-up of 23.8 (range 1.0-42.4) months, among the 35 response-evaluable pts, the IRC-assessed CR rate was 54.3% (95% CI, 36.6-71.2%), and the ORR was 88.6% (95% CI, 73.3-96.8%). According to the investigator assessment, the CR and ORR rate were 51.4% (95% CI, 34.0-68.6%) and 85.7% (95% CI, 69.7-95.2%), respectively. The median DoCR was not reached, while the median DoR were 20.1 (95% CI, 5.2-35.1) months. The median PFS was 20.8 (95% CI, 6.1-35.5) months, and the median OS was not reached with a 2-year OS rate of 93.3% (95% CI, 75.9-98.3%). Moreover, Lipo-MIT exhibited a favorable PK profile, with linear PK characteristics in the 12-18 mg/m 2 dose range. Conclusions: The CMOP regimen demonstrates a favorable PK profile, manageable safety profile, and encouraging preliminary anti-tumor activity. These results support further phase 2 and 3 trials clinical studies to confirm activity and assess efficacy in this population. Clinical trial information: NCT04548700 .