Efficacy and safety of mitoxantrone hydrochloride liposome in peripheral T-cell lymphoma: A multicenter, non-interventional, ambispective cohort real-world study

Abstract

Abstract Background: Peripheral T-cell lymphoma (PTCL) represents a heterogeneous group of aggressive lymphomas, accounting for 25%–30% of non-Hodgkin lymphomas (NHL) in China. The CHOP regimen remains the standard first-line treatment for PTCL, yet its long-term efficacy requires improvement. Relapsed or refractory (R/R) PTCL is highly aggressive with extremely poor survival outcomes, exhibiting a 3-year overall survival (OS) rate of less than 30%. This MOMENT study demonstrated promising efficacy and safety of the mitoxantrone hydrochloride liposome (Lipo-MIT)-based regimen in PTCL (J Leuk Lymphoma, 2023, 32(8): 457-464). Nevertheless, additional data are warranted to establish further validation. We previously reported updated real-world evidence for Lipo-MIT in treatment-naïve (TN) PTCL (2025 EHA, #PF949), showing a complete response (CR) rate of 48.2% and objective response rate (ORR) of 83.6%. Herein, we present updated survival outcomes for Lipo-MIT in TN-PTCL and provide the most recent real-world evidence regarding Lipo-MIT in R/R PTCL. Methods: This multicenter, non-interventional, ambispective cohort real-world study was registered at www.chictr.org.cn (ChiCTR2200062067). It enrolled adult patients diagnosed with TN or R/R PTCL. The primary endpoint was ORR. Secondary endpoints included CR rate, progression-free survival (PFS), OS, and safety. Results: As of February 8, 2025, 609 patients were enrolled, comprising 494 with relapsed/refractory PTCL (R/R PTCL) and 115 with treatment-naïve PTCL (TN-PTCL). The R/R cohort had a median age of 56 years (range: 19–86) with 62.1% males; subtypes included angioimmunoblastic T-cell lymphoma (AITL, 30.0%), extranodal NK/T-cell lymphoma (NKTCL, 25.9%), PTCL not otherwise specified (PTCL-NOS, 24.9%), ALK-negative anaplastic large cell lymphoma (ALCL, ALK-, 5.9%), ALK-positive ALCL (ALCL, ALK+, 2.8%), and other subtypes (10.5%). Advanced-stage (III–IV) disease was present in 67.0% pts, 27.9% had International prognostic index (IPI) scores 3–5, and 21.1% exhibited B symptoms. Prior therapy exposure included: ≥1 lines in all patients (50.4% first-line, 21.3% second-line, 28.3% ≥third-line), with 74.9% previously receiving anthracyclines. Patients received Lipo-MIT-containing regimens for a median of 3 cycles (range: 1–11), with median Lipo-MIT doses of 17.7 mg/m² (monotherapy: range 11.2–20.3 mg/m²; combination: range 5.4–23.3 mg/m²). Among 456 efficacy-evaluable R/R patients, the overall response rate (ORR) was 62.1% (283/456) and complete response (CR) rate was 29.2% (133/456), with ORR varying by subtype: AITL 68.6% (96/140), NKTCL 60.8% (73/120), PTCL-NOS 57.5% (65/113), ALCL ALK- 51.9% (14/27), and ALCL ALK+ 61.5% (8/13). Response rates decreased with prior lines: 68.1% (160/235) after first-line, 61.6% (61/99) after second-line, and 50.8% (62/122) after ≥third-line therapy. With a median follow-up of 6.5 months, median progression-free survival (PFS) was 9.9 months (95% CI: 7.1–12.7) and median overall survival (OS) was not reached. In the TN cohort (n=115), median follow-up was 11.6 months with median PFS of 14.6 months (95% CI: 10.8–18.3); 1-year PFS rates was 58.6%. Median OS was not reached, with 1-year OS rates of 88.0%. Safety analysis of the full cohort (n=609) revealed treatment-related adverse events (TRAEs) in 89.0% (542/609), with grade ≥3 TRAEs in 66.0%. Predominant hematologic toxicities included neutropenia (46.6%), leukopenia (42.2%), lymphopenia (34.5%), anemia (22.5%), and thrombocytopenia (23.0%). Non-hematologic TRAEs were primarily grade 1–2; no unexpected or serious adverse events were observed. Conclusion: Lipo-MIT-based regimens demonstrated favorable clinical efficacy and tolerability in both TN-PTCL and R/R PTCL, representing a promising therapeutic option. Continued follow-up for survival outcomes is ongoing, with additional results forthcoming.