Mitoxantrone Hydrochloride Liposome Containing Regimen in Patients with Adult Acute Lymphoblastic Leukemia: A Multicenter, Retrospective, Real-World Study

Background Although the initial overall response rate is high (70%-90%) in adult acute lymphoblastic leukemia (ALL) patients (pts), a large percentage of them frequently relapse. Prognosis of relapsed/refractory (R/R) ALL remains poor and there are no clear guidelines on the best treatment approach. Currently, an anthracycline-based multidrug chemotherapy regimen remains the treatment cornerstone in ALL. Mitoxantrone is a synthetic anthracenedione anti-cancer drug that is effective in lymphoma, leukemia, and other solid tumors. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics and significantly prolong the survival time of animals compared with the same dose of mitoxantrone. However, there is still a lack of systematic reports about the real-world application of PLM60 in ALL.

Methods A multicenter retrospective analysis was performed for 38 pts with newly diagnosed and R/R ALL, who received at least one cycle of PLM60-containing regimen between February 2022 and June 2023 (ChiCTR2200067172). Pts aged 18 years or older with ECOG PS 0-2 and diagnosed with ALL were eligible. Efficacy was assessed by complete remission (CR) rate, overall response rate (ORR), relapse-free survival (RFS), overall survival (OS), and correlative analyses. Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Results At the data cut-off of 15 July 2023, 38 eligible pts who received induction, consolidation or pre-transplant therapy were enrolled. The median age was 40.5 years (range 24.0-71.0), 50.0% were male, median white blood cell (WBC) count was 7.9 x 10 ⁹ /L (range 1.4-160.9) and 68.4% had B‐lineage ALL. In addition, two pts had received hematopoietic stem cell transplantation. The median dose of PLM60 in the regimen was 16.2 (range 5.4-43.2) mg/m ². Among the 23 newly diagnosed pts, the CR rate was 91.3% (21/23, 95%CI 72.0%-98.9%) and ORR was 91.3% (21/23, 95%CI 72.0%-98.9%), the ORR after induction therapy was 75.0% (6/8). The ORR was 95% and 66.7% in the WBC＜30×10 ⁹ /L and ≥30×10 ⁹ /L groups, respectively. Among the 15 R/R pts, the CR rate was 33.3% (5/15, 95%CI 11.8%-61.6%) and ORR was 46.7% (7/15, 95%CI 21.3%-73.4%), the ORR after induction therapy was 42.9% (6/14). The ORR was 57.1% and 37.5% in the WBC＜30×10 ⁹ /L and ≥30×10 ⁹ /L groups, respectively. The ORR of pts with 1 and ≥ 2 previous induction regimens was 71.4% and 25.0%, respectively. Other efficacy indicators were RFS and OS, but data are still too early and will be reported after a long-term follow-up. Treatment-related adverse events (TRAEs) of any grade occurred in 79.0% pts. Common grade 3/4 AEs included decreased neutrophil count (50.0%), thrombocytopenia (36.8%), anemia (34.2%), febrile neutropenia (5.3%). The overall safety was acceptable and controllable.

Conclusion The PLM60-containing regimen had an encouraging efficacy and showed a manageable safety profile in adult ALL with the most adverse events being hematologic toxicities.